Sufentanil is an injectable and sublingual opioid agonist of the phenylpiperidine class. Injectable sufentanil is indicated as a primary anesthetic agent for the induction and maintenance of anesthesia with 100% oxygen in patients undergoing major surgical procedures to provide favorable myocardial and cerebral oxygen balance or when extended postoperative ventilation is required, as an analgesic adjunct in the maintenance of balanced anesthesia, and for epidural anesthesia with low dose bupivacaine during labor and delivery. Sufentanil sublingual tablets are indicated for the management of acute severe pain that requires an opioid analgesic and for which alternative treatment options are inadequate in a certified, medically supervised healthcare setting. When used as balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanyl. Sufentanil has been shown to provide some attenuation of the sympathetic reflex activity in response to surgical stimuli, hemodynamic stability, and relatively rapid recovery.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Sublingual Administration
-Sublingual sufentanil tablets are only to be administered by a healthcare provider in a certified, medically supervised healthcare setting.
-Wear gloves during sublingual sufentanil administration.
-Do not use if the pouch seal is broken or if the single-dose applicator is damaged.
-Instruct the patient to not chew or swallow the tablet.
-Instruct the patient to not eat or drink and minimize talking for 10 minutes after receiving the tablet. Ice chips may be provided prior to administration if a patient experiences excessive dry mouth.
-Remove the single dose applicator from the pouch.
-Remove the white lock from the green pusher. Avoid touching the pusher before placing the applicator in the patient's mouth.
-Place the applicator tip under the tongue, and gently depress the green pusher to deliver the tablet to the sublingual space. Avoid direct mucosal contact with the applicator tip.
-Discard the applicator in biohazard waste.
-Discontinue sublingual sufentanil therapy prior to the patient leaving the medically supervised setting.
Injectable Administration
-Sufentanil injection should be administered only by persons specifically trained in the use of intravenous or epidural anesthetics and management of the respiratory effects of potent opioids. In instances of patients administered high doses of sufentanil injection, it it essential that qualified personnel and adequate facilities are available for the management of respiratory depression.
-For purposes of administering small doses of sufentanil injection, use a tuberculin syringe or equivalent.
-Monitor vital signs regularly.
-Select preanesthetic medications based upon the individual needs of the patient.
-If using neuromuscular blockade, select neuromuscular blocker compatible with patient's condition, taking into account the hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Administer IV by slow injection or continuous infusion.
Other Injectable Administration
Epidural Administration
-Verify proper placement of the needle or catheter in the epidural space prior to sufentanil administration.
-Administer with bupivacaine with or without epinephrine. Mix sufentanil and bupivacaine together before administration.
-Administer epidurally by slow injection.
-Closely monitor respiration after each epidural injection.
-If analgesia is inadequate, verify placement and integrity of the catheter prior to administration of any additional epidural medications.
Pharmacologic tolerance can develop during chronic opioid therapy. Tolerance is the need for increasing opioid doses to maintain initial pain relief. Typically, tolerance presents as a decrease in the duration of analgesia and can be managed by increasing the opioid dose or frequency. There is no limit to tolerance, thus some patients may require very large doses of opioid analgesics to control their pain. When increasing doses of analgesia are required, causes may be multi-factorial including tolerance, progression of disease, or psychologic distress.
As with other opioid agonists, the most significant adverse effect associated with sufentanil is respiratory depression. Respiratory depression is more common in elderly or debilitated patients, after therapy initiation or dosage increase, or when opioids are given with other agents that cause CNS depression. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Apnea and postoperative respiratory depression occurred in 0.3% to 1% of patients who received sufentanil intravenously for surgical anesthesia or in combination with bupivacaine 0.125% for epidural anesthesia during labor (n = 660). Bronchospasm has also been reported with injectable sufentanil in 0.3% to 1% of patients. Respiratory adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include hypoxia, bradypnea, hiccups, apnea, atelectasis, hypoventilation, respiratory distress, respiratory failure, decreased oxygen saturation, and decreased respiratory rate.
Cardiovascular effects are due to medullary vasomotor center depression and vagal nucleus stimulation by sufentanil. Sufentanil does not affect histamine release or decrease myocardial contractility. In clinical trials with injectable sufentanil, hypotension occurred 7 times more frequently with intravenous administration compared to epidural administration with bupivacaine 0.125%. The overall incidence of hypotension with injectable sufentanil during trials was 3% to 9%. Administration of benzodiazepines immediately before or after high doses of injectable sufentanil results in a decrease in mean arterial pressure and systemic vascular resistance; recovery from this effect may be prolonged. In clinical studies, 1 case of severe fetal bradycardia associated with maternal hypotension was reported within 8 minutes of injectable sufentanil administration. Sinus bradycardia and hypertension were reported in 3% to 9% of patients treated with injectable sufentanil; arrhythmia exacerbation and sinus tachycardia were reported in 0.3% to 1% of patients treated with injectable sufentanil. Cardiac arrest occurred during postmarketing observation with injectable sufentanil. During a trial of patients with moderate to severe acute postoperative pain or pain due to trauma, hypotension occurred more frequently in patients treated with sufentanil sublingual tablets (4.7%, n = 107) than in patients given placebo (3.7%, n = 54). Other cardiovascular adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include sinus tachycardia, bradycardia, hypertension, orthostatic hypotension, flushing, and abnormal electrocardiogram.
Skeletal muscle rigidity, especially chest wall rigidity (3% to 9%) and rigidity of neck and extremities, has been observed with intravenous sufentanil use. Muscle rigidity occurs more rapidly with sufentanil than fentanyl and is dependent upon the dose and rate of administration. Chest wall and abdominal muscle rigidity may significantly interfere with breathing. Muscular rigidity may occur or recur infrequently during the extended postoperative period. The incidence of muscle rigidity may be reduced by 1) administration of up to one-fourth of the full paralyzing dose of a non-depolarizing neuromuscular blocker just prior to administration of sufentanil at analgesic doses (up to 8 mcg/kg); 2) administration of a full paralyzing dose of a neuromuscular blocker after loss of consciousness when sufentanil is used in anesthesia doses (more than 8 mcg/kg) titrated slowly; or 3) simultaneous administration of sufentanil and a full paralyzing dose of a neuromuscular blocker when sufentanil is used in rapidly administered anesthetic doses more than 8 mcg/kg.
Pruritus was frequently reported in 25% of patients during controlled clinical trials with sufentanil use during surgical anesthesia or labor. Erythema was noted in 0.3% to 1% of patients. The incidence of dermatological reactions was 4 to 25 times higher among patients who received the drug epidurally for labor and delivery compared to those who received the drug intravenously during surgical anesthesia. Anaphylaxis, or anaphylactoid reactions, has been reported during postmarketing surveillance. Skin or soft tissue-related adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include pruritus, hyperhidrosis, and rash.
CNS depressant effects including postoperative drowsiness or somnolence occurred in 3% to 9% of patients who received IV sufentanil during surgical anesthesia or epidural sufentanil with bupivacaine 0.125% for analgesia during labor (n = 660). Chills occurred in 0.3% to 1% of sufentanil recipients who received the drug intravenously. During a trial of patients with moderate to severe acute postoperative pain or pain due to trauma, headache occurred more frequently in patients treated with sufentanil sublingual tablets (12.1%, n = 107) than in patients given placebo (11.1%, n = 54). Dizziness occurred in 5.6% of patients treated with sufentanil tablets and 3.7% of patients given placebo. Other nervous system adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include drowsiness or somnolence, sedation, presyncope, lethargy, and memory impairment.
Gastrointestinal adverse reactions reported during controlled clinical trials of injectable sufentanil include nausea and vomiting, which occurred in 3% to 9% of patients. During a placebo-controlled trial of patients with moderate to severe acute postoperative pain or pain due to trauma, nausea (29% vs. 22.2%) and vomiting (5.6% vs. 1.9%) occurred more frequently in patients treated with sufentanil sublingual tablets (n = 107) than in patients given placebo (n = 54). Other gastrointestinal adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include constipation, dyspepsia, flatulence, diarrhea, xerostomia, eructation, retching, abdominal discomfort, abdominal distension, upper abdominal pain, gastritis, postoperative ileus, and oral hypoesthesia.
As with other opioid agonists, sufentanil presents the potential for abuse or psychological dependence. Accidental and non-accidental overdose of this medication may occur. Physiological dependence, as evidenced by a withdrawal syndrome occurring after abrupt discontinuation of the drug, has been reported and may occur in any patient with chronic opioid therapy. Symptoms of withdrawal include nausea, diarrhea, coughing, lacrimation, yawning, sneezing, rhinorrhea, profuse sweating, twitching muscles, abdominal and muscle pain/cramps, hot and cold flashes, and piloerection. Elevations in body temperature, respiratory rate, heart rate, and blood pressure may also occur. Routine use of opioid agonists by an expectant mother can lead to depressed respiration in the newborn and a neonatal opioid withdrawal syndrome. Neonatal opioid withdrawal syndrome is estimated to occur in up to 50% of neonates born to opioid-dependent mothers. Withdrawal symptoms may include irritability, hyperactivity, abnormal sleep pattern, tremor, high-pitched crying, vomiting, diarrhea, poor feeding, failure to gain weight, rigidity, and seizures. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn. Monitor neonates exposed to opioids closely as neonatal opioid withdrawal can be life-threatening if not recognized and treated. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal.
Intraoperative muscle movement, or myoclonia, was observed in up to 1% of patients who received intravenous sufentanil during surgical anesthesia clinical trials. Muscle spasm occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials.
Opioid agonists can interfere with the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH), and by stimulating secretion of prolactin, growth hormone (GH), insulin, and glucagon. Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression). Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence (erectile dysfunction), amenorrhea, or infertility. Other various medical, physical, lifestyle, and psychological stressors may influence gonadal hormone concentrations; these stressors have not been adequately controlled for in clinical studies with opioids. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation. A drug-induced decrease in thyrotropin release leads to a decrease in thyroid hormone. Morphine and related compounds can stimulate the release of vasopressin (ADH). Hyponatremia can occur as a result of SIADH.
Opioids may interfere with the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH) and cortisol. Rarely, adrenocortical insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency.
Psychiatric adverse reactions that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include insomnia, confusion, anxiety, agitation, disorientation, euphoria, hallucinations, and mental status changes.
Serotonin syndrome has been reported in patients taking opioids at recommended doses. Patients taking opioids concomitantly with a serotonergic medication should seek immediate medical attention if they develop symptoms such as agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea. Symptoms generally present within hours to days of taking an opioid with another serotonergic agent, but may also occur later, particularly after a dosage increase. If serotonin syndrome is suspected, either the opioid and/or the other agent should be discontinued.
Renal and urinary disorders that occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials include urinary retention, urinary hesitation, oliguria, renal failure (unspecified), and decreased urine output.
Elevated hepatic enzymes occurred in 0.1% or more of patients exposed to 30 mcg or more of sublingual sufentanil during clinical trials.
Cases of opioid-induced hyperalgesia (OIH) have been reported, both with short-term and longer-term use of opioids. OIH occurs when an opioid paradoxically causes an increase in pain or an increase in sensitivity to pain. Symptoms of OIH include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Data suggests a strong biologic plausibility between opioids and OIH and allodynia. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching to a different opioid).
Hypoglycemia has been reported during opioid therapy. Most reports occurred in persons with at least 1 predisposing risk factor, such as diabetes.
Sufentanil is contraindicated for use in patients with a known hypersensitivity to sufentanil or components of the drug. Anaphylaxis has been reported with postmarketing use of sufentanil.
Sufentanil sublingual tablets are contraindicated for use in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Sufentanil use requires a clinician trained in the use of anesthetic drugs, airway management, and assisted ventilation. Sufentanil use also requires a specialized care setting. Adequate facilities for the management of postoperative respiratory depression must be available when using injectable sufentanil. Sublingual sufentanil is for use only in a certified medically supervised health care setting. Avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective dosages and minimum treatment durations needed. Monitor patients closely for signs or symptoms of respiratory depression and sedation. Patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, respiratory insufficiency, hypoxemia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive even at recommended doses. Patients with advanced age, cachexia, or debilitation are also at an increased risk for opioid-induced respiratory depression. Monitor such patients closely, particularly when initiating and titrating the opioid; consider the use of non-opioid analgesics in these patients. Opioids increase the risk of central sleep apnea (CSA) and sleep-related hypoxemia in a dose-dependent fashion. Consider decreasing the opioid dosage in patients with CSA. Respiratory depression, if left untreated, may cause respiratory arrest and death. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring and dose titration are required, particularly when CYP3A4 inhibitors or inducers are used concomitantly. Concomitant use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma sufentanil concentrations and potentiate the risk of fatal respiratory depression. Management of respiratory depression may include observation, necessary supportive measures, and opioid antagonist use when indicated.
Sufentanil sublingual tablets are contraindicated for use in patients with known or suspected GI obstruction, including paralytic ileus. Due to the effects of opioid agonists on the gastrointestinal tract, sufentanil should be used cautiously in patients with GI disease, such as ulcerative colitis (UC). Patients with UC or other inflammatory bowel disease may be more sensitive to constipation caused by opioid agonists. Opioid agonists may obscure the diagnosis or clinical course in patients with acute abdomen. As with other opioid agonists, sufentanil may cause spasm of the sphincter of Oddi. Biliary effects due to opioid agonists have resulted in increased serum amylase concentrations. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Use sufentanil with caution in geriatric or debilitated patients. Geriatric or debilitated patients are more susceptible to adverse reactions, especially sedation and respiratory depression, probably as a result of the altered distribution of the drug or decreased elimination. Initial doses may need to be reduced, and doses should be carefully titrated, taking into account analgesic effects, adverse reactions, and concomitant conditions and drugs that may increase CNS depression and depress respiration. According to the Beers Criteria, opiate agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, except in the setting of severe acute pain, since opiates can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opiate must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. In patients receiving palliative care or hospice, the balance of benefits and harms of medication management may differ from those of the general population of older adults.
Abrupt discontinuation of prolonged sufentanil therapy can result in withdrawal symptoms. Gradually taper the dosage of prolonged sufentanil therapy to avoid a withdrawal reaction. Avoid use of partial agonists (e.g., buprenorphine), mixed agonist/antagonists (e.g., nalbuphine), or pure antagonists (e.g., naloxone) in patients physically dependent on opioids, as an acute withdrawal syndrome may precipitate. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and on the administered dose of the concomitant drug. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. In addition, the use of partial agonists or mixed agonist/antagonists in patients who have received or are receiving sufentanil should be avoided as these medications may reduce the analgesic effect of sufentanil.
Avoid sufentanil use in patients with CNS depression, impaired consciousness, or coma; opioids may obscure the clinical course in a patient with a head trauma injury. Monitor patients who may be susceptible to the intracranial effect of carbon dioxide retention (e.g., those with evidence of increased intracranial pressure, brain tumor, or intracranial mass) for signs of sedation and respiratory depression, particularly when initiating sufentanil therapy. Sufentanil may reduce respiratory drive and resultant carbon dioxide retention can further increase intracranial pressure.
Any patient receiving sufentanil should be warned about the possibility of sedation and to use caution when driving or operating machinery.
Use sufentanil with caution in patients with adrenal insufficiency (i.e., Addison's disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.
Opioid agonists, such as sufentanil, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine. In patients who are unable to maintain blood pressure due to hypovolemia or dehydration, or in those who concurrently receive other agents that compromise vasomotor tone (e.g., phenothiazines or general anesthetics), opioid agonists may induce peripheral vasodilatation and severe hypotension. These effects can cause problems in patients with cardiac disease (e.g., angina, heart failure). Sufentanil should be used with caution in patients with cardiac arrhythmias or orthostatic hypotension. Sufentanil should not be used in patients with circulatory shock. Monitor patients for hypotension following sufentanil initiation or dosage titration.
Seizures can be precipitated by opioid agonists in patients with a preexisting seizure disorder. The incidence of these effects during sufentanil therapy is not known. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.
Opioid use requires an experienced clinician who is knowledgeable about the use of opioids and how to mitigate the associated risks. Opioids expose users to the risks of addiction, abuse, and misuse, which can occur at any dosage or duration. Although the risk of addiction in any individual is unknown, it can occur in persons appropriately prescribed an opioid. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each individual's risk for opioid addiction, abuse, or misuse before prescribing an opioid, and monitor for the development of these behaviors or conditions. Risks are increased in persons with a personal or family history of substance abuse (including alcoholism) or mental illness (e.g., major depression). The potential for these risks should not prevent the proper management of pain in any given individual. Persons at increased risk may be prescribed opioids but use in such persons necessitates intensive counseling about the risks and proper use of the opioid along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse and addiction are separate and distinct from physical dependence and tolerance; persons with addiction may not exhibit tolerance and symptoms of physical dependence. Opioids are sought by drug abusers and persons with addiction disorders and are subject to criminal diversion. Abuse of opioids has the potential for overdose or poisoning and death. Consider these risks when prescribing or dispensing opioids. Strategies to reduce these risks include proper product storage and control practices for controlled substances. Sublingual sufentanil is for use only in a certified medically supervised health care setting; use outside this setting can increase the risk of accidental exposure in others for whom it is not prescribed. Discontinue use of sublingual sufentanil prior to discharge or transfer from the certified medically supervised health care setting. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of an opioid for persons in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Do not use immediate-release opioids for an extended period unless the pain remains severe enough to require an opioid and for which alternative treatment options continue to be inadequate. Many acute pain conditions (e.g., pain occurring with surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
Use sufentanil cautiously in patients with renal impairment because of the renal excretion of sufentanil and its metabolites; reduce the dosage as needed, and monitor for signs of respiratory depression, sedation, and hypotension. Sufentanil can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction, or pelvic tumors.
Use sufentanil with caution in patients with hepatic disease because of the extensive hepatic metabolism; its clearance may decrease in patients with hepatic impairment. Reduce the dosage as needed, and monitor for signs of respiratory depression, sedation, and hypotension.
The clearance of sufentanil in healthy neonates is approximately one-half that in adults and children. The clearance rate of sufentanil can be further reduced by up to a third in neonates with cardiovascular disease, resulting in an increase in the elimination half-life of the drug.
There are no available data with sufentanil in human pregnancy to inform a drug-associated risk for major birth defects and miscarriage. In animal studies, embryolethality and maternal toxicity were observed in rabbits given intravenous sufentanil at 4.4 times the maximum human daily dose of 360 mcg/60 kg/day based on body surface area comparison during organogenesis. Decreased birth weight, live fetuses, and pup survival occurred in rats given intravenous sufentanil during late gestation through lactation at doses less than the human daily dose of 360 mcg. No malformations were observed in rats or rabbits at doses below the human daily dose of 360 mcg. Sufentanil is not recommended for intravenous administration or in epidural doses above those recommended during labor and obstetric delivery because of increased risks to the newborn infant after delivery. Sufentanil sublingual tablets are not recommended for use during or immediately prior to labor because oral opioid agonists may cause respiratory depression in the newborn. Opioid analgesics can prolong labor by reducing the strength and frequency of uterine contractions; however, this effect may be offset by an increased rate of cervical dilation. Further, prolonged maternal use of opioids during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for sufentanil and any potential adverse effects on the breast-fed infant from sufentanil or from the underlying maternal condition. Monitor infants exposed to sufentanil through breast milk for sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Sufentanil is excreted into breast milk. In a study of 29 women who underwent cesarean section and received sufentanil 20 mcg epidurally prior to surgery and were then randomized to receive patient-controlled epidural anesthesia with an anesthetic and sufentanil 3.75 mcg/hour plus 1.25 mcg every 20 minutes as needed or an epidural anesthetic alone, breast milk sampled over 3 days postpartum in both groups contained sufentanil. In 9 women who underwent cesarean section and received sufentanil 50 mcg epidurally immediately after delivery, sufentanil was undetectable in colostrum approximately 1 hour after the dose. Sufentanil epidural use is generally considered compatible with nursing; when used for analgesia and anesthesia during labor and delivery or when used during other surgery, the healthy term infant can safely nurse as soon as the mother is awake and alert. Sufentanil concentrations would be expected to increase over time if used intravenously over an extended period due to the long half-life of the drug. The oral bioavailability of sufentanil is unknown.
Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.
For use during general anesthesia induction and general anesthesia maintenance:
NOTE: Sufentanil injection is indicated for intravenous administration for anesthesia in patients who are intubated and ventilated.
-for use as primary anesthetic agent for the induction and maintenance of anesthesia with 100% oxygen in patients undergoing major surgery:
Intravenous dosage:
Adults: 8 to 30 mcg/kg given by slow IV injection or continuous IV infusion. May give additional doses of 0.5 to 10 mcg/kg IV as needed up to total dose of 30 mcg/kg IV for procedure.
Adolescents: 8 to 30 mcg/kg given by slow IV injection or continuous IV infusion. May give additional doses of 0.5 to 10 mcg/kg IV as needed up to total dose of 30 mcg/kg IV for procedure.
Infants and Children: 10 to 25 mcg/kg IV. May give additional doses of 25 to 50 mcg IV based on response to initial dose and as determined by changes in vital signs.
Neonates: 10 to 25 mcg/kg IV. May give additional doses of 25 to 50 mcg IV based on response to initial dose and as determined by changes in vital signs. The clearance of sufentanil in healthy neonates is approximately one-half that in children; sufentanil clearance is further reduced by up to one-third in neonates with cardiovascular disease.
-for the maintenance of balanced general anesthesia as an analgesic adjunct (expected duration of anesthesia 1 to 2 hours):
Intravenous dosage:
Adults: 1 to 2 mcg/kg IV given as 10 to 25 mcg IV as needed or continuous IV infusion up to total dose of 1 mcg/kg/hour of expected surgical time. May administer 75% or more of total dose prior to intubation. Usually given in combination with nitrous oxide/oxygen.
-for the maintenance of balanced general anesthesia as an analgesic adjunct (expected duration of anesthesia 2 to 8 hours):
Intravenous dosage:
Adults: 2 to 8 mcg/kg IV given as 10 to 50 mcg IV as needed or continuous IV infusion up to total dose of 1 mcg/kg/hour of expected surgical time. May administer 75% or more of total dose prior to intubation. Usually given in combination with nitrous oxide/oxygen.
For use as obstetric anesthesia, specifically epidural anesthesia during labor and delivery:
Epidural dosage:
Adult females: 10 to 15 mcg epidurally with 10 mL of bupivacaine 0.125% with or without epinephrine. May repeat dose every 1 hour as needed until delivery up to 3 doses.
For the treatment of acute, severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate:
NOTE: Sublingual sufentanil is indicated for use in a certified, medically supervised healthcare setting.
Sublingual dosage:
Adults: 30 mcg sublingually every 1 hour as needed for up to 72 hours. Max: 360 mcg/24 hours.
Maximum Dosage Limits:
-Adults
30 mcg/kg/procedure IV for general anesthesia; 1 mcg/kg/hour IV total dose for general anesthesia adjunct; 12 tablets/day SL.
-Geriatric
30 mcg/kg/procedure IV for general anesthesia; 1 mcg/kg/hour IV total dose for general anesthesia adjunct; 12 tablets/day SL.
-Adolescents
30 mcg/kg/procedure IV for general anesthesia; 1 mcg/kg/hour IV total dose for general anesthesia adjunct. Safety and efficacy of sublingual tablets have not been established.
-Children
25 mcg/kg IV. Safety and efficacy of sublingual tablets have not been established.
-Infants
25 mcg/kg IV. Safety and efficacy of sublingual tablets have not been established.
-Neonates
25 mcg/kg IV. Safety and efficacy of sublingual tablets have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; dose should be modified depending on the clinical response and degree of hepatic impairment.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; dose should be modified depending on the clinical response and degree of renal impairment.
*non-FDA-approved indication
Acebutolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of opioid agonists with pyrilamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with pyrilamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Dextromethorphan; Doxylamine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Hydrocodone: (Major) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of opioid agonists with pyrilamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with pyrilamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acrivastine; Pseudoephedrine: (Major) Avoid coadministration of opioid agonists with acrivastine due to the risk of additive CNS depression.
Adagrasib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if adagrasib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of adagrasib is necessary. If adagrasib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a strong CYP3A inhibitor like adagrasib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If adagrasib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Alosetron: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alprazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Alvimopan: (Moderate) Patients should not take alvimopan if they have received therapeutic doses of opiate agonists for more than seven consecutive days immediately before initiation of alvimopan therapy. Patients recently exposed to opioids are expected to be more sensitive to the effects of mu-opioid receptor antagonists and may experience adverse effects localized to the gastrointestinal tract such as abdominal pain, nausea, vomiting, and diarrhea.
Amide local anesthetics: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Amiloride: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Amiodarone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amiodarone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amiodarone is necessary. If amiodarone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like amiodarone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amiodarone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amitriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Amlodipine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Atorvastatin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Benazepril: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Celecoxib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Olmesartan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Valsartan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Amobarbital: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Amoxapine: (Major) The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if clarithromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of clarithromycin is necessary. If clarithromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like clarithromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If clarithromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Amphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Amphetamine; Dextroamphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Amphetamines: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Anticholinergics: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Apalutamide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if apalutamide must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with apalutamide is necessary; consider increasing the dose of sufentanil injection as needed. If apalutamide is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Apomorphine: (Major) Apomorphine may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Apraclonidine: (Minor) Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as opiate agonists. Although no specific drug interactions were identified with systemic agents and apraclonidine during clinical trials, apraclonidine can cause dizziness and somnolence.
Aprepitant, Fosaprepitant: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if aprepitant/fosaprepitant must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of aprepitant/fosaprepitant is necessary. If aprepitant/fosaprepitant is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like aprepitant/fosaprepitant can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If aprepitant/fosaprepitant is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Aripiprazole: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Armodafinil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if armodafinil must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with armodafinil is necessary; consider increasing the dose of sufentanil injection as needed. If armodafinil is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and armodafinil is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Articaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Asciminib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if asciminib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like asciminib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If asciminib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Asenapine: (Moderate) Concomitant use of opioid agonists with asenapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with asenapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of sufentanil with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of sufentanil with carisoprodol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with carisoprodol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Atazanavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Atazanavir; Cobicistat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Atenolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Atenolol; Chlorthalidone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Atropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Avacopan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if avacopan must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of avacopan is necessary. If avacopan is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like avacopan can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If avacopan is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Azelastine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Azelastine; Fluticasone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Azilsartan; Chlorthalidone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Baclofen: (Major) Concomitant use of sufentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Barbiturates: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Belladonna; Opium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Belumosudil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if belumosudil must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of belumosudil is necessary. If belumosudil is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like belumosudil can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If belumosudil is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Belzutifan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if belzutifan must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with belzutifan is necessary; consider increasing the dose of sufentanil injection as needed. If belzutifan is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A substrate and belzutifan is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with sufentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of benzhydrocodone with sufentanil to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking sufentanil, reduce initial dosage and titrate to clinical response. If sufentanil is prescribed in a patient taking benzhydrocodone, use a lower initial dose and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Fluids or other measures to counter hypotension should be available. Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and sufentanil because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of sufentanil in patients receiving methylene blue or within 14 days of stopping treatment with methylene blue due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benzphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benztropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Berotralstat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if berotralstat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of berotralstat is necessary. If berotralstat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like berotralstat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If berotralstat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Beta-blockers: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Betaxolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Bethanechol: (Moderate) Bethanechol facilitates intestinal and bladder function via parasympathomimetic actions. Opiate agonists impair the peristaltic activity of the intestine. Thus, these drugs can antagonize the beneficial actions of bethanechol on GI motility.
Bexarotene: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if bexarotene must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of sufentanil injection as needed. If bexarotene is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Bicalutamide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if bicalutamide must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like bicalutamide can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If bicalutamide is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Bismuth Subsalicylate: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Bisoprolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Bosentan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if bosentan must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with bosentan is necessary; consider increasing the dose of sufentanil injection as needed. If bosentan is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Brexanolone: (Moderate) Concomitant use of brexanolone with CNS depressants like the opiate agonists may increase the likelihood or severity of adverse reactions related to sedation and additive CNS depression. Monitor for excessive sedation, dizziness, and a potential for loss of consciousness during brexanolone use.
Brexpiprazole: (Major) Concomitant use of opioid agonists with brexpiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with brexpiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Brigatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if brigatinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with brigatinib is necessary; consider increasing the dose of sufentanil injection as needed. If brigatinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Brimonidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Brimonidine; Brinzolamide: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Brimonidine; Timolol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Brompheniramine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Bumetanide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Bupivacaine Liposomal: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bupivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bupivacaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bupivacaine; Lidocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bupivacaine; Meloxicam: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Buprenorphine: (Major) Buprenorphine is a mixed opiate agonist/antagonist with strong affinity for the mu-receptor that may partially block the effects of full mu-receptor opiate agonists and reduce analgesic effects. In some cases of acute pain, trauma, or during surgical management, opiate-dependent patients receiving buprenorphine maintenance therapy may require concurrent treatment with opiate agonists, such as sufentanil. In these cases, health care professionals must exercise caution in opiate agonist dose selection, as higher doses of an opiate agonist may be required to compete with buprenorphine at the mu-receptor. Management strategies may include adding a short-acting opiate agonist to achieve analgesia in the presence of buprenorphine, discontinuation of buprenorphine and use of an opiate agonist to avoid withdrawal and achieve analgesia, or conversion of buprenorphine to methadone while using additional opiate agonists if needed. Closely monitor patients for CNS or respiratory depression. When buprenorphine is used for analgesia, avoid co-use with opiate agonists. Buprenorphine may cause withdrawal symptoms in patients receiving chronic opiate agonists as well as possibly potentiate CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Buprenorphine; Naloxone: (Major) Buprenorphine is a mixed opiate agonist/antagonist with strong affinity for the mu-receptor that may partially block the effects of full mu-receptor opiate agonists and reduce analgesic effects. In some cases of acute pain, trauma, or during surgical management, opiate-dependent patients receiving buprenorphine maintenance therapy may require concurrent treatment with opiate agonists, such as sufentanil. In these cases, health care professionals must exercise caution in opiate agonist dose selection, as higher doses of an opiate agonist may be required to compete with buprenorphine at the mu-receptor. Management strategies may include adding a short-acting opiate agonist to achieve analgesia in the presence of buprenorphine, discontinuation of buprenorphine and use of an opiate agonist to avoid withdrawal and achieve analgesia, or conversion of buprenorphine to methadone while using additional opiate agonists if needed. Closely monitor patients for CNS or respiratory depression. When buprenorphine is used for analgesia, avoid co-use with opiate agonists. Buprenorphine may cause withdrawal symptoms in patients receiving chronic opiate agonists as well as possibly potentiate CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Bupropion; Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of sufentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from sufentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Buspirone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of sufentanil, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use is imperative, reduce the dose of one or both drugs if clinically indicated.
Butalbital; Acetaminophen: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Butorphanol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as sufentanil. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Cannabidiol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Capivasertib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if capivasertib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of capivasertib is necessary. If capivasertib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like capivasertib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If capivasertib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Capsaicin; Metaxalone: (Major) Concomitant use of opioid agonists with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of opioid pain medication with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of metaxalone and opioid agonists increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Carbamazepine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if carbamazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of sufentanil injection as needed. If carbamazepine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbidopa; Levodopa; Entacapone: (Major) COMT inhibitors may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Carbinoxamine: (Moderate) Concomitant use of opioid agonists with carbinoxamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with carbinoxamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cariprazine: (Moderate) Concomitant use of opioid agonists like sufentanil with cariprazine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cariprazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Carisoprodol: (Major) Concomitant use of sufentanil with carisoprodol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with carisoprodol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Carteolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Carvedilol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol increases the seizure risk in patients taking opiate agonists. Also, tramadol can cause additive CNS depression and respiratory depression when used with opiate agonists; avoid concurrent use whenever possible. If used together, extreme caution is needed, and a reduced tramadol dose is recommended.
Cenobamate: (Moderate) Concomitant use of sufentanil with cenobamate may cause excessive sedation and somnolence. Limit the use of sufentanil with cenobamate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Additionally, concurrent use of sufentanil with cenobamate may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of cenobamate may increase the risk of opioid-related adverse reactions, such as fatal respiratory depression. Cenobamate induces CYP3A4; sufentanil is a CYP3A4 substrate.
Ceritinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ceritinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ceritinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Cetirizine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cetirizine; Pseudoephedrine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chloramphenicol: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if chloramphenicol must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of chloramphenicol is necessary. If chloramphenicol is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like chloramphenicol can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If chloramphenicol is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Chlorcyclizine: (Moderate) Concomitant use of opioid agonists with chlorcyclizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorcyclizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlordiazepoxide: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlordiazepoxide; Clidinium: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chloroprocaine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
Chlorothiazide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Chlorpheniramine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpromazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Chlorthalidone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Chlorzoxazone: (Major) Concomitant use of sufentanil with chlorzoxazone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with chlorzoxazone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cimetidine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cimetidine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary. If cimetidine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like cimetidine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cimetidine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ciprofloxacin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ciprofloxacin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. If ciprofloxacin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like ciprofloxacin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ciprofloxacin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Citalopram: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
Clarithromycin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if clarithromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of clarithromycin is necessary. If clarithromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like clarithromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If clarithromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Clemastine: (Moderate) Concomitant use of opioid agonists with clemastine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clemastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Clevidipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with clevidipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving clevidipine.
Clobazam: (Major) Concomitant use of sufentanil with clobazam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with clobazam to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if clobazam must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with clobazam may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of clobazam may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Clobazam induces CYP3A4; sufentanil is a CYP3A4 substrate.
Clomipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Clonazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Clonidine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Clopidogrel: (Moderate) Coadministration of opioid agonists, such as sufentanil, delay and reduce the absorption of clopidogrel resulting in reduced exposure to active metabolites and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Coadministration of intravenous morphine decreased the Cmax and AUC of clopidogrel's active metabolites by 34%. Time required for maximal inhibition of platelet aggregation (median 3 hours vs. 1.25 hours) was significantly delayed; times up to 5 hours were reported. Inhibition of platelet plug formation was delayed and residual platelet aggregation was significantly greater 1 to 4 hours after morphine administration.
Clorazepate: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Clozapine: (Moderate) Sufentanil should be combined cautiously with clozapine due to the potential for additive depressant effects, respiratory depression, or hypotension. Combining clozapine with opiate agonists may also lead to reduced intestinal motility or bladder function.
Cobicistat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Codeine; Phenylephrine; Promethazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Codeine; Promethazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
COMT inhibitors: (Major) COMT inhibitors may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Conivaptan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if conivaptan must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of conivaptan is necessary. If conivaptan is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a moderate CYP3A inhibitor like conivaptan can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If conivaptan is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Crizotinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if crizotinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of crizotinib is necessary. If crizotinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like crizotinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If crizotinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Cyclobenzaprine: (Major) Concomitant use of sufentanil with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death. Additionally, concomitant use may result in serotonin syndrome. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Cyclosporine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cyclosporine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cyclosporine is necessary. If cyclosporine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like cyclosporine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cyclosporine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Cyproheptadine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dabrafenib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dabrafenib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of sufentanil injection as needed. If dabrafenib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Dalfopristin; Quinupristin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dalfopristin; quinupristin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of dalfopristin; quinupristin is necessary. If dalfopristin; quinupristin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like dalfopristin; quinupristin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If the streptogramin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Danazol: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if danazol must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like danazol can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If danazol is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Dantrolene: (Major) Concomitant use of sufentanil with dantrolene may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with dantrolene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Daridorexant: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if daridorexant must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of daridorexant is necessary. If daridorexant is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like daridorexant can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If daridorexant is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Darifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when darifenacin, an anticholinergic drug for overactive bladder, is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known.
Darunavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Darunavir; Cobicistat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Deferasirox: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if deferasirox must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of sufentanil injection as needed. If deferasirox is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Delavirdine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if delavirdine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like delavirdine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If delavirdine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Desflurane: (Moderate) Concurrent use with opiate agonists can decrease the minimum alveolar concentration (MAC) of desflurane needed to produce anesthesia.
Desipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including opiate agonists. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
Deutetrabenazine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Dexamethasone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dexamethasone must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with dexamethasone is necessary; consider increasing the dose of sufentanil injection as needed. If dexamethasone is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and dexamethasone is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexchlorpheniramine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexmedetomidine: (Moderate) Concomitant use of opioid agonists with dexmedetomidine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with dexmedetomidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexmethylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextroamphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Diazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If parental diazepam is used with an opiate agonist, reduce the opiate agonist dosage by at least 1/3. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Dicyclomine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Difelikefalin: (Major) Avoid concomitant use of opioids and other CNS depressants, such as difelikefalin. Concomitant use can increase the risk of respiratory depression, hypotension, profound sedation, and death. If alternate treatment options are inadequate and coadministration is necessary, limit dosages and durations to the minimum required, monitor patients closely for respiratory depression and sedation, and consider prescribing naloxone for the emergency treatment of opioid overdose.
Diltiazem: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if diltiazem must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of diltiazem is necessary. If diltiazem is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like diltiazem can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If diltiazem is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Dimenhydrinate: (Moderate) Concomitant use of opioid agonists with dimenhydrinate may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dimenhydrinate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Diphenhydramine; Ibuprofen: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Diphenhydramine; Naproxen: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Diphenhydramine; Phenylephrine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Dolasetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dorzolamide; Timolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Doxepin: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Doxylamine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Doxylamine; Pyridoxine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Dronabinol: (Moderate) Concomitant use of opioid agonists with dronabinol may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dronabinol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dronedarone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dronedarone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of dronedarone is necessary. If dronedarone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like dronedarone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If dronedarone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Droperidol: (Major) Concomitant use of opioid agonists with droperidol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with droperidol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Duvelisib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if duvelisib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like duvelisib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If duvelisib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Efavirenz: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if efavirenz must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with efavirenz is necessary; consider increasing the dose of sufentanil injection as needed. If efavirenz is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if efavirenz must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with efavirenz is necessary; consider increasing the dose of sufentanil injection as needed. If efavirenz is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if efavirenz must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with efavirenz is necessary; consider increasing the dose of sufentanil injection as needed. If efavirenz is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Elagolix: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if elagolix must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of sufentanil injection as needed. If elagolix is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if elagolix must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of sufentanil injection as needed. If elagolix is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Elbasvir; Grazoprevir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if grazoprevir must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of grazoprevir is necessary. If grazoprevir is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like grazoprevir can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If grazoprevir is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ivacaftor must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ivacaftor is necessary. If ivacaftor is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like ivacaftor can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ivacaftor is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Eluxadoline: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if eluxadoline must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like eluxadoline can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If eluxadoline is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if cobicistat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of cobicistat is necessary. If cobicistat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like cobicistat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If cobicistat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Enasidenib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if enasidenib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with enasidenib is necessary; consider increasing the dose of sufentanil injection as needed. If enasidenib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and enasidenib is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Encorafenib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if encorafenib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with encorafenib is necessary; consider increasing the dose of sufentanil injection as needed. If encorafenib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Entacapone: (Major) COMT inhibitors may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Enzalutamide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if enzalutamide must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with enzalutamide is necessary; consider increasing the dose of sufentanil injection as needed. If enzalutamide is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Erythromycin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if erythromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like erythromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If erythromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Escitalopram: (Moderate) Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including sufentanil.
Esketamine: (Major) Concomitant use of opioid agonists with esketamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with esketamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep. Educate patients about the risks and symptoms of excessive CNS depression.
Eslicarbazepine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if eslicarbazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of sufentanil injection as needed. If eslicarbazepine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Esmolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Estazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Eszopiclone: (Major) Concomitant use of opioid agonists with eszopiclone may cause excessive sedation, somnolence, and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Limit the use of opioid pain medications with eszopiclone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur. Educate patients about the risks and symptoms of excessive CNS depression.
Ethacrynic Acid: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking opioids. Alcohol consumption may result in additive CNS depression and may increase the risk for opioid overdose. Consider the patient's use of alcohol when prescribing opioid medications. If the patient is unlikely to be compliant with avoiding alcohol, consider prescribing naloxone especially if additional risk factors for opioid overdose are present.
Etomidate: (Major) Concomitant use of sufentanil with other CNS depressants can potentiate the effects of sufentanil on respiration, CNS depression, sedation, and hypotension. Both the magnitude and duration of CNS and cardiovascular effects may be enhanced. Less etomidate is generally required under these circumstances.
Etravirine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if etravirine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of sufentanil injection as needed. If etravirine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Everolimus: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if everolimus must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of everolimus is necessary. If everolimus is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like everolimus can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If everolimus is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Fedratinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fedratinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of fedratinib is necessary. If fedratinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a CYP3A4 inhibitor like fedratinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fedratinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Felodipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with felodipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving felodipine.
Fenfluramine: (Moderate) Concomitant use of opioid agonists with fenfluramine may cause excessive sedation and somnolence. Limit the use of opioid agonists with fenfluramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fesoterodine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when fesoterodine, an anticholinergic drug for overactive bladder is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known.
Fexinidazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fexinidazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of fexinidazole is necessary. If fexinidazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like fexinidazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fexinidazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Flavoxate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Flibanserin: (Moderate) Concomitant use of opioid agonists with flibanserin may cause excessive sedation and somnolence. Limit the use of opioid pain medication with flibanserin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Fluconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fluconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. If fluconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like fluconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fluconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Fluoxetine: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fluoxetine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of fluoxetine is necessary. If fluoxetine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like fluoxetine has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fluoxetine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fluoxetine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Fluphenazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Flurazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Fluvoxamine: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fluvoxamine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of fluvoxamine is necessary. If fluvoxamine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like fluvoxamine has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fluvoxamine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fluvoxamine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Fosphenytoin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fosphenytoin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with fosphenytoin is necessary; consider increasing the dose of sufentanil injection as needed. If fosphenytoin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Fostamatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fostamatinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of fostamatinib is necessary. If fostamatinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like fostamatinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fostamatinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Furosemide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Gabapentin: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of sufentanil with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Glycerol Phenylbutyrate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if glycerol phenylbutyrate must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with glycerol phenylbutyrate is necessary; consider increasing the dose of sufentanil injection as needed. If glycerol phenylbutyrate is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Granisetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Grapefruit juice: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if grapefruit juice is regulary consumed. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if patient consumes grapefruit juice. If grapefruit juice intake is significantly reduced or stopped, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like grapefruit juice can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If grapefruit juice intake is significantly reduced or stopped, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Guanfacine: (Moderate) Concomitant use of opioid agonists with guanfacine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with guanfacine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Haloperidol: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as sufentanil. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hydrocodone: (Major) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Hydromorphone: (Major) Concomitant use of hydromorphone with other central nervous system (CNS) depressants, such as other opiate agonists, can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Hydroxyzine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hyoscyamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of sufentanil in patients receiving methylene blue or within 14 days of stopping treatment with methylene blue due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Idelalisib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if idelalisib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If idelalisib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Iloperidone: (Moderate) Concomitant use of iloperidone with other centrally-acting medications such as opiate agonists, may increase both the frequency and the intensity of adverse effects including drowsiness, sedation, and dizziness.
Imatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if imatinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like imatinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If imatinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Imipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Indacaterol; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Indapamide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when indapamide is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Indinavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Isavuconazonium: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isavuconazonium must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like isavuconazonium can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isavuconazonium is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Isocarboxazid: (Major) The use of sufentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Isoflurane: (Moderate) The magnitude and duration of central nervous system and cardiovascular effects may be enhanced when sufentanil is administered to patients receiving isoflurane. Prolonged recovery time may occur. When used together, doses of sufentanil and/or isoflurane should be reduced and titrated carefully.
Isoniazid, INH: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isoniazid must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like isoniazid has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isoniazid is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isoniazid must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like isoniazid has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isoniazid is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifampin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of sufentanil injection as needed. If rifampin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Isoniazid, INH; Rifampin: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isoniazid must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like isoniazid has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isoniazid is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifampin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of sufentanil injection as needed. If rifampin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Isradipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with isradipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving isradipine.
Istradefylline: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if istradefylline 40 mg daily must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of istradefylline 40 mg daily is necessary. If istradefylline is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. Coadministration can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If istradefylline is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if itraconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of itraconazole is necessary. If itraconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like itraconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If itraconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ivacaftor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ivacaftor must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ivacaftor is necessary. If ivacaftor is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like ivacaftor can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ivacaftor is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ketamine: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when sufentanil is given concurrently with ketamine. Monitor for CNS depression, hypotension, and respiratory depression during use together. Prolonged recovery time may occur. Postoperative confusional states may occur during the recovery period during use of ketamine. The patient should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.
Ketoconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ketoconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ketoconazole is necessary. If ketoconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like ketoconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ketoconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Labetalol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if clarithromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of clarithromycin is necessary. If clarithromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like clarithromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If clarithromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Lapatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lapatinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of lapatinib is necessary. If lapatinibis discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like lapatinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If lapatinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Larotrectinib: (Moderate) Consider a reduced dose of sufentanil with frequent monitoring for respiratory depression and sedation if concurrent use of larotrectinib is necessary. If larotrectinib is discontinued, consider increasing the sufentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a sensitive CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like larotrectinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If larotrectinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Lasmiditan: (Moderate) Concomitant use of sufentanil with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of sufentanil with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Lefamulin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if oral lefamulin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of oral lefamulin is necessary. If oral lefamulin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong/moderate/weak CYP3A4 inhibitor like oral lefamulin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil; an interaction is not expected with intravenous lefamulin. If oral lefamulin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Lemborexant: (Moderate) Concomitant use of sufentanil with lemborexant may cause excessive sedation and somnolence. Limit the use of sufentanil with lemborexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Lenacapavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lenacapavir must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of lenacapavir is necessary. If lenacapavir is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a moderate CYP3A inhibitor like lenacapavir can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If lenacapavir is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Letermovir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if letermovir must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of letermovir is necessary. If letermovir is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a CYP3A4 inhibitor like letermovir can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If letermovir is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Levamlodipine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Levobunolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Levocetirizine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Levoketoconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ketoconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ketoconazole is necessary. If ketoconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like ketoconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ketoconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Levomilnacipran: (Moderate) If concomitant use of sufentanil and levomilnacipran is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Lidocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lidocaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lidocaine; Prilocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Linezolid: (Major) Avoid concomitant use of sufentanil in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Lisdexamfetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lithium: (Moderate) If concomitant use of sufentanil and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and sufentanil. Lofexidine can potentiate the effects of CNS depressants.
Lonafarnib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lonafarnib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of lonafarnib is necessary. If lonafarnib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like lonafarnib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If lonafarnib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Loop diuretics: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lopinavir; Ritonavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Lorazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lorcaserin: (Moderate) If concomitant use of sufentanil and lorcaserin is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Lorlatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lorlatinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with lorlatinib is necessary; consider increasing the dose of sufentanil injection as needed. If lorlatinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Loxapine: (Moderate) Concomitant use of opioid agonists, such as sufentanil, with loxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with loxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lumacaftor; Ivacaftor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ivacaftor must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ivacaftor is necessary. If ivacaftor is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like ivacaftor can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ivacaftor is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lumacaftor; ivacaftor must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with lumacaftor; ivacaftor is necessary; consider increasing the dose of sufentanil injection as needed. If lumacaftor; ivacaftor is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Lumacaftor; Ivacaftor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lumacaftor; ivacaftor must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with lumacaftor; ivacaftor is necessary; consider increasing the dose of sufentanil injection as needed. If lumacaftor; ivacaftor is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Lumateperone: (Moderate) Concomitant use of opioid agonists like sufentanil with lumateperone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with lumateperone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lurasidone: (Moderate) Concomitant use of opioid agonists like sufentanil with lurasidone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with lurasidone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Maprotiline: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Maribavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if maribavir must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of maribavir is necessary. If maribavir is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like maribavir can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If maribavir is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Mavacamten: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mavacamten must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of sufentanil injection as needed. If mavacamten is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Melatonin: (Moderate) Concomitant use of opioid agonists with melatonin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with melatonin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Mepivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Meprobamate: (Moderate) Concomitant use of sufentanil with meprobamate can potentiate the effects of sufentanil on respiration, CNS depression, sedation, and hypotension. Both the magnitude and duration of CNS and cardiovascular effects may be enhanced. Postoperative respiratory depression associated with sufentanil may also be augmented. If used together, a reduction in the dose of one or both drugs may be needed.
Meropenem: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if meropenem must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of sufentanil injection as needed. If meropenem is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Meropenem; Vaborbactam: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if meropenem must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of sufentanil injection as needed. If meropenem is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Metaxalone: (Major) Concomitant use of opioid agonists with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of opioid pain medication with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of metaxalone and opioid agonists increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Methadone: (Major) Concomitant use of methadone with another CNS depressant can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Methamphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid concomitant use of sufentanil in patients receiving methylene blue or within 14 days of stopping treatment with methylene blue due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Methocarbamol: (Major) Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a skeletal muscle relaxant, use a lower initial dose of the opiate and titrate to clinical response. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Methohexital: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Methscopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Methyldopa: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methylene Blue: (Major) Avoid concomitant use of sufentanil in patients receiving methylene blue or within 14 days of stopping treatment with methylene blue due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration.
Methylphenidate Derivatives: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Metoclopramide: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Metolazone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Metoprolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Metyrosine: (Moderate) The concomitant administration of metyrosine with opiate agonists can result in additive sedative effects.
Midazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Mifepristone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mifepristone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If mifepristone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Milnacipran: (Moderate) If concomitant use of sufentanil and milnacipran is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently.
Mirtazapine: (Major) Concomitant use of opioid agonists with mirtazapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with mirtazapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Mitapivat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mitapivat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with mitapivat is necessary; consider increasing the dose of sufentanil injection as needed. If mitapivat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A substrate and mitapivat is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Mitotane: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mitotane must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with mitotane is necessary; consider increasing the dose of sufentanil injection as needed. If mitotane is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Mobocertinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mobocertinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with mobocertinib is necessary; consider increasing the dose of sufentanil injection as needed. If mobocertinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A substrate and mobocertinib is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Modafinil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if modafinil must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with modafinil is necessary; consider increasing the dose of sufentanil injection as needed. If modafinil is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Molindone: (Moderate) Concomitant use of opioid agonists like sufentanil with molindone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with molindone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Monoamine oxidase inhibitors: (Major) The use of sufentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Morphine: (Moderate) Concomitant use of sufentanil with morphine can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
Morphine; Naltrexone: (Moderate) Concomitant use of sufentanil with morphine can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
Nabilone: (Major) Avoid coadministration of opioid agonists with nabilone due to the risk of additive CNS depression.
Nadolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Nafcillin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nafcillin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with nafcillin is necessary; consider increasing the dose of sufentanil injection as needed. If nafcillin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Nalbuphine: (Major) Avoid the concomitant use of nalbuphine and opiate agonists, such as sufentanil. Nalbuphine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Nalbuphine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of nalbuphine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of sufentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from sufentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nebivolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Nebivolol; Valsartan: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Nefazodone: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nefazodone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of nefazodone is necessary. If nefazodone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like nefazodone has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like nefazodone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If nefazodone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Nelfinavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Neostigmine; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if netupitant must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of netupitant is necessary. If netupitant is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like netupitant can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If netupitant is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Nevirapine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nevirapine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of sufentanil injection as needed. If nevirapine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Nicardipine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nicardipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of nicardipine is necessary. If nicardipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like nicardipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If nicardipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
NIFEdipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with nifedipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving nifedipine.
Nilotinib: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nilotinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of nilotinib is necessary. If nilotinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like nilotinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If nilotinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Nimodipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with nimodipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving nimodipine.
Nirmatrelvir; Ritonavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Nirogacestat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nirogacestat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of nirogacestat is necessary. If nirogacestat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a moderate CYP3A inhibitor like nirogacestat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If nirogacestat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Nisoldipine: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with nisoldipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving nisoldipine.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Nortriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Odevixibat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if odevixibat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with odevixibat is necessary; consider increasing the dose of sufentanil injection as needed. If odevixibat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and odevixibat is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Olanzapine: (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olanzapine; Fluoxetine: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if fluoxetine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of fluoxetine is necessary. If fluoxetine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like fluoxetine has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fluoxetine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If fluoxetine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olanzapine; Samidorphan: (Contraindicated) Salmidorphan is contraindicated in patients who are using opiate agonists or undergoing acute opioid withdrawal. Salmidorphan increases the risk of precipitating acute opioid withdrawal in patients dependent on opioids. Before initiating salmidorphan, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations, if a salmidorphan-treated patient requires opiates for anesthesia or analgesia, discontinue salmidorphan. The opiate agonist should be administered by properly trained individual(s), and the patient properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations, if a salmidorphan-treated patient requires opiate agonist treatment (e.g., for analgesia) discontinue salmidorphan at least 5 days before opioid treatment. Salmidorphan, as an opioid antagonist, may cause opioid treatment to be less effective or ineffective shortly after salmidorphan discontinuation. (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oliceridine: (Major) Concomitant use of oliceridine with sufentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with sufentanil to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Olutasidenib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if olutasidenib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with olutasidenib is necessary; consider increasing the dose of sufentanil injection as needed. If olutasidenib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and olutasidenib is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Omaveloxolone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if omaveloxolone must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with omaveloxolone is necessary; consider increasing the dose of sufentanil injection as needed. If omaveloxolone is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and omaveloxolone is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifabutin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifabutin is necessary; consider increasing the dose of sufentanil injection as needed. If rifabutin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ondansetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Opicapone: (Major) COMT inhibitors may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Oritavancin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if oritavancin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with oritavancin is necessary; consider increasing the dose of sufentanil injection as needed. If oritavancin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and oritavancin is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Orphenadrine: (Major) Concomitant use of sufentanil with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Osilodrostat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if osilodrostat must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of osilodrostat is necessary. If osilodrostat is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like osilodrostat can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If osilodrostat is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Oxazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxcarbazepine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if oxcarbazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of sufentanil injection as needed. If oxcarbazepine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Oxybutynin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Oxymorphone: (Major) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Respiratory depression, hypotension, profound sedation, or coma may result from combination therapy. Prior to concurrent use of oxymorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxymorphone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxymorphone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Slowly titrate the dose as necessary for adequate pain relief and monitor for sedation or respiratory depression.
Ozanimod: (Major) When sufentanil is administered to patients who have received ozanimod within 14 days, monitor patients for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension as needed. Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported rarely with sufentanil. An active metabolite of ozanimod inhibits MAO-B. The MAOI interactions with opioids may also manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Pacritinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pacritinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like pacritinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If pacritinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Palbociclib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if palbociclib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of palbociclib is necessary. If palbociclib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like palbociclib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If palbociclib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Paliperidone: (Moderate) Drugs that can cause CNS depression such as opiate agonists, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Advise patients to avoid driving or engaging in other activities requiring mental alertness as directed by their healthcare provider after administration of sufentanil.
Palonosetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Paroxetine: (Moderate) If concomitant use of sufentanil and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Pazopanib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pazopanib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like pazopanib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If pazopanib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Pegvisomant: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Pentazocine; Naloxone: (Major) Avoid the concomitant use of pentazocine and opiate agonists, such as sufentanil. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Pentobarbital: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Perampanel: (Moderate) Concomitant use of opioid agonists with perampanel may cause excessive sedation and somnolence. Limit the use of opioid pain medications with perampanel to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Perindopril; Amlodipine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Perphenazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Perphenazine; Amitriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Pexidartinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pexidartinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of sufentanil injection as needed. If pexidartinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Phenelzine: (Major) The use of sufentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Phenobarbital: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Phenothiazines: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Phentermine; Topiramate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if topiramate must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of sufentanil injection as needed. If topiramate is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Phenytoin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if phenytoin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with phenytoin is necessary; consider increasing the dose of sufentanil injection as needed. If phenytoin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pimozide: (Moderate) Concomitant use of sufentanil with other CNS depressants, such as pimozide, can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects.
Pindolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Pirtobrutinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pirtobrutinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of pirtobrutinib is necessary. If pirtobrutinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like pirtobrutinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil.
Posaconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if posaconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If posaconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Pramipexole: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Pramlintide: (Major) Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications with the potential to slow GI motility, such as opiate agonists, should be used with caution, if at all, with pramlintide until more data are available from the manufacturer. Monitor blood glucose.
Prasugrel: (Moderate) Consider the use of a parenteral anti-platelet agent for patients with acute coronary syndrome who require concomitant opioid agonists. Coadministration of opioid agonists with prasugrel delays and reduces the absorption of prasugrel's active metabolite due to slowed gastric emptying.
Pregabalin: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of sufentanil with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Prilocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Prilocaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Primidone: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Procarbazine: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
Prochlorperazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Promethazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Promethazine; Dextromethorphan: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Promethazine; Phenylephrine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Propantheline: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Propranolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Protease inhibitors: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Protriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Pseudoephedrine; Triprolidine: (Moderate) Concomitant use of opioid agonists with triprolidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with triprolidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Quazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Quetiapine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Quinine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if quinine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like quinine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If quinine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ramelteon: (Moderate) Concomitant use of opioid agonists with ramelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with ramelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ranolazine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ranolazine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ranolazine is necessary. If ranolazine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like ranolazine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ranolazine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Rasagiline: (Major) Avoid concomitant use of sufentanil in patients receiving rasagiline or within 14 days of stopping treatment with rasagiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Remimazolam: (Major) Concomitant use of opioid agonists with remimazolam may cause respiratory depression, hypotension, profound sedation, and death. Titrate the dose of remimazolam to the desired clinical response and continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation.
Repotrectinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if repotrectinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with repotrectinib is necessary; consider increasing the dose of sufentanil injection as needed. If repotrectinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ribociclib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ribociclib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ribociclib is necessary. If ribociclib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like ribociclib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ribociclib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ribociclib; Letrozole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ribociclib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ribociclib is necessary. If ribociclib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like ribociclib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ribociclib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Rifabutin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifabutin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifabutin is necessary; consider increasing the dose of sufentanil injection as needed. If rifabutin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Rifampin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifampin must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of sufentanil injection as needed. If rifampin is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Rifapentine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifapentine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of sufentanil injection as needed. If rifapentine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Risperidone: (Moderate) Concomitant use of sufentanil with other CNS depressant, such as risperidone, can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
Ritlecitinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ritlecitinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ritlecitinib is necessary. If ritlecitinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a moderate CYP3A inhibitor like ritlecitinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ritlecitinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Ritonavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ropinirole: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Ropivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Rotigotine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rucaparib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rucaparib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of rucaparib is necessary. If rucaparib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like rucaparib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If rucaparib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Safinamide: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Saquinavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Scopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Secobarbital: (Major) Concomitant use of sufentanil with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if barbiturates must be administered. If concurrent use of sufentanil injection is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. Additionally, concurrent use of sufentanil with barbiturates may decrease sufentanil plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Monitor for signs of opioid withdrawal. Discontinuation of barbiturates may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; sufentanil is a CYP3A4 substrate.
Selegiline: (Major) Avoid concomitant use of sufentanil in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Serotonin-Receptor Agonists: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Serotonin-Receptor Antagonists: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sertraline: (Moderate) If concomitant use of sufentanil and sertraline is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Sevoflurane: (Moderate) The magnitude and duration of central nervous system and cardiovascular effects may be enhanced when sufentanil is administered to patients receiving sevoflurane. Prolonged recovery time may occur. When used together, doses of sufentanil and/or sevoflurane should be reduced and titrated carefully.
Sodium Oxybate: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if taurursodiol must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with taurursodiol is necessary; consider increasing the dose of sufentanil injection as needed. If taurursodiol is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and taurursodiol is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Solifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Sotalol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Sotorasib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if sotorasib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with sotorasib is necessary; consider increasing the dose of sufentanil injection as needed. If sotorasib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Spironolactone: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if spironolactone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like spironolactone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If spironolactone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if spironolactone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like spironolactone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If spironolactone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
St. John's Wort, Hypericum perforatum: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if St. John's Wort must be administered. Consider an increased dose of sufentanil injection and monitor for evidence of opioid withdrawal and serotonin syndrome if coadministration with St. John's Wort is necessary. If St. John's Wort is discontinued, consider reducing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of respiratory depression. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like St. John's Wort has resulted in serotonin syndrome. In addition, sufentanil is a CYP3A4 substrate, and coadministration with a CYP3A4 inducer like St. John's Wort can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Stiripentol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of sufentanil resulting in an increased risk of adverse reactions and/or decreased efficacy. Sufentanil is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dalfopristin; quinupristin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of dalfopristin; quinupristin is necessary. If dalfopristin; quinupristin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like dalfopristin; quinupristin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If the streptogramin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sumatriptan; Naproxen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Suvorexant: (Moderate) Concomitant use of opioid agonists with suvorexant may cause excessive sedation and somnolence. Limit the use of opioid pain medications with suvorexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tapentadol: (Major) Concomitant use of tapentadol with sufentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of tapentadol with sufentanil to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tasimelteon: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tazemetostat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if tazemetostat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of sufentanil injection as needed. If tazemetostat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tecovirimat: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if tecovirimat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with tecovirimat is necessary; consider increasing the dose of sufentanil injection as needed. If tecovirimat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tedizolid: (Major) Avoid concomitant use of sufentanil in patients receiving tedizolid or within 14 days of stopping treatment with tedizolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Telmisartan; Amlodipine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if amlodipine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like amlodipine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If amlodipine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Telotristat Ethyl: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if telotristat ethyl must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with telotristat ethyl is necessary; consider increasing the dose of sufentanil injection as needed. If telotristat ethyl is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and telotristat ethyl is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Temazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tetrabenazine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Tetracaine: (Major) Due to the central nervous system depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists. Excitation or depression of the CNS may be the first manifestation of CNS toxicity. Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. After each local anesthetic injection, careful and constant monitoring of ventilation adequacy, cardiovascular vital signs, and the patient's state of consciousness is advised.
Tezacaftor; Ivacaftor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ivacaftor must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ivacaftor is necessary. If ivacaftor is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like ivacaftor can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ivacaftor is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Thalidomide: (Major) Avoid coadministration of opioid agonists with thalidomide due to the risk of additive CNS depression.
Thiazide diuretics: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Thioridazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Thiothixene: (Moderate) Concomitant use of opioid agonists like sufentanil with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ticagrelor: (Moderate) Coadministration of opioid agonists, such as sufentanil, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population.
Timolol: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Tipranavir: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tizanidine: (Major) Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a skeletal muscle relaxant, use a lower initial dose of the opiate and titrate to clinical response. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tolcapone: (Major) COMT inhibitors may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Tolterodine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug, such as tolterodine. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Topiramate: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if topiramate must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of sufentanil injection as needed. If topiramate is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Torsemide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Tramadol: (Major) Concomitant use of tramadol increases the seizure risk in patients taking opiate agonists. Also, tramadol can cause additive CNS depression and respiratory depression when used with opiate agonists; avoid concurrent use whenever possible. If used together, extreme caution is needed, and a reduced tramadol dose is recommended.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol increases the seizure risk in patients taking opiate agonists. Also, tramadol can cause additive CNS depression and respiratory depression when used with opiate agonists; avoid concurrent use whenever possible. If used together, extreme caution is needed, and a reduced tramadol dose is recommended.
Trandolapril; Verapamil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if verapamil must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of verapamil is necessary. If verapamil is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like verapamil can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If verapamil is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tranylcypromine: (Major) The use of sufentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Trazodone: (Moderate) Because of the potential risk and severity of excessive sedation, somnolence, and serotonin syndrome, caution should be observed when administering sufentanil with trazodone. Limit the use of opioid pain medications with trazodone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Inform patients taking this combination of the possible increased risks and monitor for the emergence of excessive CNS depression and serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Triamterene: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when triamterene is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when triamterene is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Triazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tricyclic antidepressants: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Trifluoperazine: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Trihexyphenidyl: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like opiate agonists, may potentiate the effects of either trimethobenzamide or the opiate agonist.
Trimipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Triprolidine: (Moderate) Concomitant use of opioid agonists with triprolidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with triprolidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Trofinetide: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if trofinetide must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of trofinetide is necessary. If trofinetide is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like trofinetide can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If trofinetide is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Trospium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when trospium, an anticholinergic drug for overactive bladder, is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known.
Tucatinib: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if tucatinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of tucatinib is necessary. If tucatinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like tucatinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If tucatinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Valerian, Valeriana officinalis: (Moderate) Concomitant use of opioid agonists with valerian may cause excessive sedation and somnolence. Limit the use of opioid pain medication with valerian to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Valproic Acid, Divalproex Sodium: (Moderate) Concomitant use of opioid agonists with valproic acid may cause excessive sedation and somnolence. Limit the use of opioid pain medications with valproic acid to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as sufentanil, could be expected with concurrent use. Use caution, and monitor therapeutic effects of sufentanil when coadministered with vemurafenib.
Venlafaxine: (Moderate) If concomitant use of sufentanil and venlafaxine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Verapamil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if verapamil must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of verapamil is necessary. If verapamil is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like verapamil can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If verapamil is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Vilazodone: (Moderate) Because of the potential risk and severity of excessive sedation, somnolence, and serotonin syndrome, caution should be observed when administering sufentanil with vilazodone. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Inform patients taking this combination of the possible increased risks and monitor for the emergence of excessive CNS depression and serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Viloxazine: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if viloxazine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of viloxazine is necessary. If viloxazine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like viloxazine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If viloxazine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Vonoprazan: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if vonoprazan must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like vonoprazan can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If vonoprazan is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Vonoprazan; Amoxicillin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if vonoprazan must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like vonoprazan can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If vonoprazan is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if clarithromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of clarithromycin is necessary. If clarithromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like clarithromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If clarithromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if vonoprazan must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like vonoprazan can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If vonoprazan is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Voriconazole: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if voriconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of voriconazole is necessary. If voriconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like voriconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If voriconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with vortioxetine. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Voxelotor: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if voxelotor must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of voxelotor is necessary. If voxelotor is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a moderate CYP3A inhibitor like voxelotor can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If voxelotor is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Zaleplon: (Major) Concomitant use of opioid agonists with zaleplon may cause excessive sedation, somnolence, and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Limit the use of opioid pain medications with zaleplon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur. Educate patients about the risks and symptoms of excessive CNS depression.
Ziconotide: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Ziprasidone: (Moderate) Because of the potential for additive sedation and CNS depression, caution should be observed when administering sufentanil with ziprasidone. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. There are case reports of serotonin syndrome with use of ziprasidone postmarketing but causality is not established. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Zolpidem: (Major) Concomitant use of opioid agonists with zolpidem may cause excessive sedation, somnolence, and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Limit the use of opioid pain medications with zolpidem to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur. Educate patients about the risks and symptoms of excessive CNS depression. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.
Zuranolone: (Major) Avoid concomitant use of opioids and other CNS depressants, such as zuranolone. Concomitant use can increase the risk of respiratory depression, hypotension, profound sedation, and death. If alternate treatment options are inadequate and coadministration is necessary, limit dosages and durations to the minimum required, monitor patients closely for respiratory depression and sedation, and consider prescribing naloxone for the emergency treatment of opioid overdose.
Sufentanil is an opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principle therapeutic action of sufentanil is analgesia and sedation, thought to be mediated through opioid-specific receptors throughout the central nervous system. Like all full opioid agonists, there is no ceiling effect to analgesia. When used as balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanyl. The response to sufentanil is dose-dependent, with analgesia predominating at intravenous doses less than 8 mcg/kg and deep anesthesia produced at doses of 8 mcg/kg or more. Sufentanil attenuates the sympathetic response to surgical stress. The catecholamine response, especially norepinephrine, is further attenuated at intravenous sufentanil doses of 25 to 30 mcg/kg, with hemodynamic stability and preservation of favorable myocardial oxygen balance. Anesthetic doses of sufentanil maintain cardiac output, with slight reduction in systemic vascular resistance during the initial postoperative period.
Sufentanil is administered intravenously, epidurally, or sublingually. The pharmacokinetics of sufentanil can be described as a 3-compartment model. It is 93% protein bound, primarily to alpha1-acid glycoprotein. The liver and small intestine are the major sites of metabolism. The elimination half-life after intravenous administration is 164 minutes in adults and adolescents. The mean half-life and mean apparent plasma clearance are 13.4 hours and 108 L/hour, respectively, after a single sublingual tablet dose. Approximately 80% of intravenously administered drug is excreted within 24 hours and only 2% is eliminated as unchanged drug.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Sufentanil is a substrate for cytochrome P450 (CYP) 3A4.
-Route-Specific Pharmacokinetics
Oral Route
The relative bioavailability of a single sufentanil sublingual administration to a 1-minute IV infusion of 30 mcg is 53%. Sublingual Cmax values were 17-fold lower compared to IV administration. After a single sufentanil sublingual administration, the average Cmax of 63.1 pg/mL and mean AUC of 278 hours x pg/mL occur at a median Tmax of 1 hour. After 12 multiple hourly doses over 11 hours, the geometric mean for the AUC within a dosing interval and Cmax values were increased by 3.7- and 2.3-fold compared to single-dose administration. Steady-state plasma concentrations were achieved after 7 doses.
Intravenous Route
Duration of effect is dose-related.
Other Route(s)
Epidural Route
The onset of analgesia after an epidural dose of 10 to 15 mcg sufentanil with bupivacaine 0.125% with epinephrine occurs within 10 minutes with duration of 1 to 2 hours. Subsequent equivalent doses tend to have a shorter duration. The duration of initial doses of sufentanil plus bupivacaine with epinephrine is approximately 95 minutes, and of subsequent doses, 70 minutes. After epidural administration of incremental doses totaling 5 to 40 mcg sufentanil during labor and delivery, maternal and neonatal sufentanil plasma concentrations were at or near 0.05 to 0.1 ng/mL, and were slightly higher in mothers than in their infants.
-Special Populations
Renal Impairment
The clearance of sufentanil was not affected by mild or moderate renal impairment.
Pediatrics
The protein binding of sufentanil is 79% in neonates. The clearance of sufentanil in healthy neonates is approximately one-half that in adults and children. The clearance rate of sufentanil can be further reduced by up to one-third in neonates with cardiovascular disease. Relative to adults and adolescents, the elimination half-life of sufentanil is shorter in infants and children (97 minutes) and longer in neonates (434 minutes).
Gender Differences
The clearance of sufentanil was not affected by gender.
Ethnic Differences
The clearance of sufentanil was not affected by race.