Alfentanil is a synthetic opiate agonist that is used primarily in anesthesia. Alfentanil is a member of the phenylpiperidine class of opiate agonists and is a derivative of fentanyl. Alfentanil has significantly different pharmacokinetics and pharmacodynamics than fentanyl or sufentanil. Fentanyl is 5-8 times more potent than alfentanil. Alfentanil has a faster onset and shorter duration of action than fentanyl. In addition, alfentanil is less lipophilic than fentanyl but is still substantially more lipophilic than morphine. Alfentanil is widely used as an anesthetic or adjuvant to anesthesia, especially in settings where hemodynamic stability is critical (e.g., cardiovascular surgery). Alfentanil is useful in attenuating the hemodynamic response to intubation and is useful in anesthesia because it helps maintain cardiovascular stability. Alfentanil alone does not provide reliable amnestic effects or adequate anesthetic depth for general surgery. The use of inhaled anesthetics and/or hypnotics may be required. The respiratory depressant effects of alfentanil must be taken into consideration when alfentanil is given to critically ill patients. However, the duration of sedation and respiratory depression is shorter than that seen with fentanyl or sufentanil. Alfentanil has analgesic effects and may be used in pain management of intensive care and postoperative patients; although, it is rarely given for extended periods. Only personnel specifically trained in the use of intravenous and general anesthetics should administer alfentanil. The FDA approved alfentanil in 1986.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Alfentanil is administered intravenously and should only be given by individuals trained in the administration of general anesthetics and the management of the respiratory effects of potent opioids. Pulse oximetry or some other means for measuring respiratory function is recommended.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration.
Intravenous Administration
Intravenous injection
-Do not use IV without the availability of appropriate opiate antagonist and equipment to administer oxygen and control respiration.
-Dilute in 0.9% Sodium Chloride Injection or % Dextrose Injection before use.
-Infuse IV slowly over 3 minutes. Injections rates of < 1 minute are associated with an increased incidence of hypotension.
Intravenous infusion
-Do not use IV without the availability appropriate opiate antagonist and equipment to administer oxygen and control respiration.
-Infusions may be diluted in 0.9% Sodium Chloride, 5% Dextrose, 5% Dextrose and 0.9 % Sodium Chloride,, or Lactated Ringers Injection to a concentration of 25-80 mcg/mL.
-Continuous infusions longer than 5 days have not been studied.
Other Injectable Administration
Epidural Administration
-This route of administration should only be used by specially trained health care professionals.
-May be given as an intermittent bolus or continuous infusion.
-Prior to administration, an opiate antagonist and facilities for administration of oxygen and control of respiration should be available. The patient should be in a setting where adequate monitoring is possible.
-Placement of the epidural catheter and administration should be at a site near the dermatomes covering the field of pain to decrease dose requirements and increase specificity. Alfentanil produces only segmental analgesic effects and should only be used when the catheter tip is close to the incisional dermatome.
-Unopened solutions should be discarded if a precipitate is present that does not disappear with shaking.
Epidural injection
-After ensuring proper placement of the needle or catheter, inject appropriate dose into the epidural space. Monitor patient for at least 24 hours after each dose.
-Alfentanil is not usually given repeatedly in bolus form due to its short duration of action. However, in certain situations the short duration of action may be of benefit.
Continuous epidural infusion
-A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Patients should be monitored for several days following implantation of the device.
-If dilution of the injection is necessary, preservative-free 0.9% Sodium Chloride injection is recommended. Preservative-free solutions may be stored refrigerated up to 1 week provided that refrigeration is continuous and begins immediately after mixing. Once removed from the refrigerator, the solution should be used within 24 hours.
-Filling of the infusion device reservoir should only be done by fully trained and qualified health care professionals. Strict aseptic technique must be used. Withdraw dose from the ampule through a 5-micrometer (or smaller pore diameter) microfilter to avoid contamination with glass or other particles. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdose.
-To avoid exacerbation of severe pain or reflux of CSF into the reservoir, depletion of the reservoir should be avoided.
One of the most significant adverse effects associated with alfentanil is respiratory depression. Postoperative respiratory depression occurred in 1% to 3% of 785 patients who received alfentanil during general anesthesia induction or maintenance in controlled and open label clinical trials. Hypoventilation results from a dose-dependent decrease in sensitivity to carbon dioxide in the brainstem. Opioid-induced respiratory depression causes a reduction in the slope of the ventilatory and occlusion pressure responses to carbon dioxide, a rightward shift of the minute ventilatory response to hypercarbia, an increase in the apneic threshold and resting end-tidal carbon dioxide, and decreased hypoxia ventilatory drive. Apnea was reported in 3% to 9% of patients during clinical trials. Alfentanil can potentially cause postoperative respiratory depression or apnea leading to respiratory arrest. Respiratory depression is more common in elderly or debilitated patients. Symptomatic respiratory depression should be treated cautiously with an opiate antagonist such as naloxone. Alfentanil has been associated with delayed respiratory depression occurring approximately 45 minutes after the end of prolonged surgery. Rare adverse respiratory reactions with a probable causal relationship to alfentanil include bronchospasm (less than 1%), hypercarbia (0.3% to 1%), and laryngospasm (0.3% to 1%).
Gastrointestinal effects of opiate agonists are common. Nausea/vomiting was seen in 28% and 18% of patients, respectively, who received alfentanil during induction and maintenance of general anesthesia in controlled and open label clinical trials (n = 785). Nausea and vomiting are more common during gynecological surgery. Constipation and decreased gastric emptying and bowel motility are mediated by peripheral opioid receptors in the gut and central effects on the vagus nerve; constipation is rarely a concern given the short-term use of alfentanil in most settings.
Cardiovascular adverse reactions to alfentanil are common. In controlled and open label clinical trials (n = 785), hypertension occurred in 18% of patients treated with alfentanil during general anesthesia induction or maintenance. Other reported effects include arrhythmia exacerbation or bradycardia (14%), sinus tachycardia (12%), and hypotension (10%). Asystole has occurred. The occurrence of hypotension with alfentanil is associated with rapid administration and hypovolemia. Cardiac effects of alfentanil are due to medullary vasomotor center depression and vagal nucleus stimulation. Alfentanil does not affect histamine release or decrease myocardial contractility. Administration of diazepam immediately before or following high doses of alfentanil produces hypotension due to vasodilation. Recovery from this effect may be prolonged. Reduction in cardiac output is usually secondary to bradycardia. Administration of anticholinergic agents such as atropine or vagolytic neuromuscular blocking agents may decrease the incidence of bradycardia.
Alfentanil-induced chest wall rigidity occurred in 17% of patients treated with alfentanil during general anesthesia induction and maintenance in controlled and open label clinical trials (n = 785). Other skeletal muscle movements were noted in up to 9% of patients. Dose-dependent muscle rigidity occurs more rapidly with alfentanil than fentanyl or sufentanil. Chest wall and abdominal muscle rigidity may significantly interfere with breathing. Alfentanil initial bolus doses of 20 mcg/kg IV may cause chest wall rigidity; induction doses of > 130 mcg/kg will consistently cause immediate chest wall rigidity and requires the use of skeletal muscle relaxants to prevent this effect. Approximately 45% of newborn infants develop chest wall rigidity, with interference of respiration in some patients, at bolus doses of 9-15 mcg/kg IV. In infants, administration of muscle relaxants is required with alfentanil. In addition to chest wall rigidity, alfentanil may cause abdominal muscle rigidity; flexion of the fingers, wrists, and elbows; extension of the toes, ankles, knees and hips; contraction of neck muscles; immobility of the head; laryngospasm; and clenching of the jaw. Skeletal muscle rigidity of the neck and extremities has been observed during post-marketing surveillance. Pre-treatment with muscle relaxants or benzodiazepines can significantly reduce muscle rigidity.
Seizures have been reported with alfentanil use in patients with a history of seizure disorders. Severe muscle stiffness of thoracic, abdominal and limbs with associated myoclonia and vertical nystagmus may be confused with seizures. In a review of 127 patient EEGs, patients receiving large doses of alfentanil for anesthesia did not show any seizure activity.
CNS depressant effects are seen with alfentanil therapy. Dizziness was observed in 3-9% of patients who were treated with alfentanil during induction and maintenance of general anesthesia in controlled and open label clinical trials. Drowsiness or sedation (1-3%), confusion (0.3-1%), euphoria (0.3-1%), shivering (0.3-1%), headache (0.3-1%), blurred vision (1-3%), were also seen postoperatively. Disconjugate gaze has been reported. The level of postoperative drowsiness is less with alfentanil than with sufentanil (3-9%).
Adverse effects reported rarely in 0.3-1% of alfentanil recipients during induction and maintenance of general anesthesia in controlled and open label clinical trials include pruritus, urticaria, and pain at the injection site (injection site reaction). Anaphylaxis or anaphylactoid reactions, as well as other allergic events, have been observed during post-marketing experience.
Urinary retention has been reported during the use of other opiate agonists. The incidence of urinary retention occurring in patients who have received alfentanil during general anesthesia, conscious sedation, monitored anesthesia care, or during epidural administration is unknown.
Pharmacologic tolerance to the analgesic affects of opiate agonists including alfentanil may occur in some patients. Tolerance is the need for increasing alfentanil doses to maintain initial pain relief. Typically, tolerance presents as a decrease in the duration of analgesia and is managed by increasing alfentanil 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 psychological distress.
As with other opioid agonists, alfentanil 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 alfentanil 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.
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.
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.
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.
Alfentanil should only be administered by health care professionals trained in anesthesiology and the management of pain and who are familiar with the respiratory effects of strong opiate agonists.
Due to the effects of opiate agonists on the gastrointestinal tract, alfentanil should be used cautiously in patients with GI disease including GI obstruction or ileus, ulcerative colitis, or pre-existing constipation. Opiate agonists may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Patients with acute ulcerative colitis (UC) or other inflammatory bowel disease may be more sensitive to the constipating effects of opiate agonists. Although opiate agonists are contraindicated for use in patients with diarrhea secondary to poisoning or infectious diarrhea, antimotility agents have been used successfully in these patients. If possible, opiate agonists should not be given until the toxic substance has been eliminated.
Serious, fatal, or life-threatening respiratory depression has been reported with the use of opioids, even at recommended dosages. Alfentanil use requires a clinician trained in the use of anesthetic drugs, airway management, and assisted ventilation. Alfentanil use also requires a specialized care setting in monitored anesthesia care; ensure care team members not involved in the conduct of the surgical or diagnostic procedure are available for monitoring persons receiving monitored anesthesia care. Monitor oxygen saturation continuously. Resuscitative and intubation equipment, oxygen, and opioid antagonists must be readily available. 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 including vital signs, particularly when initiating and titrating alfentanil and during coadministration with other CNS depressants. Hypotension and prolonged respiratory depression and sedation may result from alfentanil coadministration with other CNS depressants. To reduce the risk of respiratory depression, proper dosing and titration of alfentanil are essential. 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. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma alfentanil concentrations and potentiate the risk of fatal respiratory depression. Management of respiratory depression may include close observation, supportive measures, and opioid antagonist use when indicated.
Alfentanil and other opiate agonists can cause urinary retention and oliguria. Patients more prone to these effects include those with bladder obstruction, pelvic tumors, prostatic hypertrophy, urethral stricture, or renal disease. Drug accumulation or prolonged duration of action can occur in patients with hepatic disease receiving alfentanil. In acute situations, patients require close monitoring to avoid excessive toxicity. Patients with chronic liver or renal impairment may require less frequent dosing intervals due to decreases in alfentanil protein binding.
Alfentanil should be used with extreme caution in patients with head trauma or with increased intracranial pressure (ICP). Rapid administration of high-dose opiate agonists may transiently elevate intracranial pressure and reduce cerebral perfusion pressures. These events are associated with opiate-induced lowering of mean arterial pressure, which stimulates a regulatory response to increase cerebral blood flow leading to increased ICP. Respiratory depression can produce cerebral hypoxia and raise CSF pressure, which is unrelated to but may exaggerate the injury. Opiate analgesics, especially in high doses, can precipitate seizures in patients with a preexisting seizure disorder.
Opiate agonists, including alfentanil, can stimulate vasovagal and vasomotor responses that may produce sinus bradycardia or decreases in blood pressure leading to reduced cardiac output. These symptoms could be troublesome in patients with cardiac disease (e.g., angina, heart failure), cardiac arrhythmias, or hypovolemia. Alfentanil can also exacerbate hypotension, especially when rapidly infused (i.e., over < 1 minute). Alfentanil does not decrease myocardial contractility. Reductions in cardiac output are usually secondary to bradycardia.
Use of alfentanil has been reported in infants and children, however, it is not currently indicated in children < 12 years of age. The half-life of alfentanil may be decreased in pediatric patients resulting in a need for more frequent dosing versus adults. Neonates have a decreased level of alpha-1-acidglycoprotein leading to decreased protein binding of medications; however, the effect on dosage requirements in neonates is unclear. Infants younger than 6 months of age may be given opiate agonists but must be closely monitored for apnea until 24 hours after their last dose. The Agency for Health Care Policy and Research Clinical Practice Guideline suggests close monitoring of children up to 1 year of age. Children weighing < 50 kg may be more sensitive to the effects of opiate agonists and require body weight dosing of opiate agonists. Whenever possible analgesia should be administered to a pediatric patient through a noninvasive route (i.e., orally or through an existing IV line). Intramuscular administration of analgesic medications, including opiate agonists, to children sends them the message that to achieve pain relief more pain must be given. This can lead to denial of pain by fearful children.
Available data with alfentanil use during pregnancy are insufficient to inform a drug-associated risk for birth defects and miscarriage. A continuous infusion (30 mcg/kg/hour followed by 30 mcg/kg/hour bolus doses as needed) was administered via an extradural catheter to 16 women undergoing vaginal delivery. Apgar scores were 7 or more at 1 minute for all 16 infants, although the Amiel-Tison test revealed neonatal hypotonia. None of the infants demonstrated abnormal feeding habits or behavioral changes after further evaluation. In animal reproduction studies, decreased birth weights and increased mortality occurred in the offspring of pregnant rats given alfentanil during gestation and throughout lactation at 9 times the human dose of 335 mcg/kg/procedure. Alfentanil was embryocidal when given to pregnant rabbits during organogenesis at 72.6 times the human dose of 335 mcg/kg/procedure. No malformations occurred in rats or rabbits given alfentanil during organogenesis. Alfentanil is not recommended for use during and immediately before labor when other analgesic techniques are more appropriate. Opioids can prolong labor and obstetric delivery by temporarily reducing the strength, duration, and frequency of uterine contractions. This effect is not consistent and may be offset by an increased rate of cervical dilatation, which may shorten labor. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in the neonate. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. An opioid antagonist (e.g., naloxone) should be available for reversal of opioid-induced respiratory depression in the neonate. Further, prolonged maternal use of opioids during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). Monitor the exposed neonate for withdrawal symptoms, including irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight, and manage accordingly. 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 alfentanil and any potential adverse effects on the breast-fed infant from alfentanil or the underlying maternal condition. Monitor infants exposed to alfentanil through breast milk for excess 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.
Females may be less sensitive to anesthesia than men and may require increased doses of anesthetic agents during surgery. Women tend to report awareness during surgery more frequently than men. In a study of patients receiving propofol, alfentanil, and nitrous oxide, women woke significantly faster after anesthesia ended than men. The time to eye opening after anesthesia and response to verbal commands was also shorter in women.
Geriatric patients are more sensitive to the analgesic effects of opiate agonists as they experience higher peak serum levels and a longer duration of pain relief. Also, elderly patients are more susceptible to adverse reactions from opiate agonists; especially sedation and respiratory depression probably as a result of the altered distribution of the drug and decreased elimination. The clearance of alfentanil in patients more than 65 years of age may be reduced up to 30%. Initial doses of opiate agonists may need to be reduced, and doses should be carefully titrated, taking into account analgesic effects and adverse reactions. 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 the 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.
Morphine and related opiates can produce spasm of the sphincter of Oddi. Alfentanil, since it is a member of a different chemical group, is less likely to produce this effect. Nevertheless, alfentanil should be used cautiously in patients with biliary tract disease, or in those who are undergoing surgery of the biliary tract.
Abrupt discontinuation of prolonged alfentanil therapy (i.e., > 3-5 days) can result in withdrawal symptoms (see Adverse Reactions). Patients should be gradually tapered off alfentanil to avoid a withdrawal reaction.
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 prescribing the drug in the smallest appropriate quantity. 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.
Any patient receiving an opiate agonist should be warned about the possibility of sedation and to use caution when driving or operating machinery.
Several factors contraindicate the use of alfentanil by epidural administration. These include: infection at the injection site or documented bacteremia, platelet abnormalities, thrombocytopenia < 100,000/mm3, increased bleeding time, uncontrolled coagulopathy, anticoagulant therapy, presence of tumor at the injection site and any other drug therapy or medical condition that may contraindicate administration of alfentanil by this route.
Although true opiate agonist hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to alfentanil should not receive other opiate agonists of the phenylpiperidine subclass (meperidine, sufentanil, fentanyl). It is possible to treat these patients with an opioid agonist from the phenanthrene subclass (including oxycodone, codeine and hydromorphone) or the diphenylheptane subclass (methadone).
The use of alfentanil in patients who have received MAOI therapy within 14 days is not recommended. The potential for interaction appears to be idiosyncratic with poorly understood contributing factors. Although in vitro assay studies have not been undertaken and published literature is inconsistent, it has been postulated that alfentanil may be a weak serotonin reuptake inhibitor. The manufacturer states that alfentanil use with MAOIs has resulted in rare reports of serious untoward reactions. It is not known if coadministration of alfentanil with other drugs known to have MAOI activity may result in serotonergic side effects (see Drug Interactions). Caution is advised until more data are available. If used concomitantly, appropriate monitoring and ready availability of vasodilators and beta-blockers for the treatment of hypertension are indicated.
Use alfentanil 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.
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: Appropriately reduce the initial alfentanil dose for elderly and debilitated patients. In one clinical trial, the dose of alfentanil required to produce anesthesia as determined by appearance of delta waves in EEG was 40% lower in geriatric patients than the dose needed for healthy young patients. Consider the effect of the initial dose when determining supplemental doses.
NOTE: Use lean body weight to calculate the alfentanil dose for patients who weigh more than 20% above their ideal total body weight.
Intravenous dosage:
Adults: 130-245 mcg/kg IV over 3 minutes as induction. Use maintenance doses of 0.5-1.5 mcg/kg/minute or give a general anesthetic. Total dose is dependent on duration of procedure. Assisted or controlled ventilation is required. Reduce concentration of inhalation agents by 30-50% for the initial hour. At these doses, truncal rigidity should be expected and a muscle relaxant should be utilized. Changes in vital signs that indicate a response to surgical stress or lessening of anesthesia may be controlled by increasing alfentanil IV infusion rate to a maximum of 4 mcg/kg/minute and/or administration of a bolus dose of 7 mcg/kg IV. If changes are not controlled by 3 bolus doses given over a 5-minute period, a barbiturate, vasodilator, and/or inhalation agent should be used. Infusion rates should be adjusted downward in the absence of these signs until there is some response to surgical stimulation. Within the last 15 minutes of surgery, 7 mcg/kg IV doses or a potent inhalation agent should be administered in response to lessening of anesthesia. Alfentanil infusions should be discontinued at least 10-15 minutes prior to the end of surgery.
-for patients spontaneously breathing/assisted ventilation:
Intravenous dosage:
Adults: 8-20 mcg/kg IV over 3 minutes with maintenance doses of 3-5 mcg/kg IV over 3 minutes every 5-20 minutes or 0.5-1 mcg/kg/minute by IV infusion. Total doses range 8-40 mcg/kg.
-for patients with assisted or controlled ventilation to attenuate the response to laryngoscopy and intubation:
Incremental intravenous injection dosage:
Adults: 20-50 mcg/kg IV over 3 minutes with maintenance doses of 5-15 mcg/kg IV over 3 minutes every 5-20 minutes. Total dose required is up to 75 mcg/kg.
-for patients with assisted or controlled ventilation to provide continued attenuation of response to intubation and incision:
NOTE: Required infusion rates are variable and should be titrated to the desired clinical effect.
Continuous intravenous infusion dosage:
Adults: 50-75 mcg/kg IV over 3 minutes then 0.5-3 mcg/kg/minute (average rate 1-1.5 mcg/kg/minute). After the induction dose, alfentanil infusion rates should be decreased by 30-50% for the first hour of maintenance. Changes in vital signs that indicate a response to surgical stress or lessening of anesthesia may be controlled by increasing alfentanil IV infusion rate to a maximum of 4 mcg/kg/minute and/or administration of a bolus dose of 7 mcg/kg IV. If changes are not controlled by 3 bolus doses given over a 5-minute period, a barbiturate, vasodilator, and/or inhalation agent should be used. Infusion rates should be adjusted downward in the absence of these signs until there is some response to surgical stimulation. Within the last 15 minutes of surgery, 7 mcg/kg IV doses or a potent inhalation agent should be administered in response to lessening of anesthesia. Alfentanil infusions should be discontinued at least 10-15 minutes prior to the end of surgery.
For procedural sedation or monitored anesthesia care sedation in the sedated, responsive, and spontaneously breathing patient:
Intravenous dosage:
Adults: 3 to 8 mcg/kg IV over 3 minutes. Maintenance doses should be 3 to 5 mcg/kg IV every 5 to 20 minutes or continuous infusions of 0.25 to 1 mcg/kg/min. Total dose ranges 3 to 40 mcg/kg. In monitored anesthesia care sedation, alfentanil infusions may be continued until the end of the procedure.
For the epidural management of postoperative, severe pain* in the intensive care setting:
Epidural dosage*:
Adults: 250-1000 mcg epidurally as an initial bolus dose then 150-300 mcg/hour maintenance infusion. Doses should be adjusted based upon the patient's level of pain and response to therapy.
Maximum Dosage Limits:
-Adults
The maximum dosage is dependent on indication for therapy.
-Elderly
The maximum dosage is dependent on indication for therapy.
-Adolescents
The maximum dosage is dependent on indication for therapy.
-Children
Safe and effective use has not been established.
Patients with Hepatic Impairment Dosing
Dose should be modified depending on the clinical response and degree of hepatic impairment; no quantitative recommendations are available.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acebutolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
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. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when alfentanil is given concurrently with dichloralphenazone, a mild sedative/hypnotic agent. Postoperative respiratory depression may be enhanced or prolonged.
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; Oxycodone: (Major) Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone 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 a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of adagrasib is necessary. If adagrasib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like adagrasib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If adagrasib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 alfentanil with almotriptan. Inform patients taking this combination of the possible increased risk 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 alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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 amiloride is administered with alfentanil. 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) Alfentanil is a substrate of CYP3A4. Amiodarone is an inhibitor of CYP3A4. If these drugs are coadministered, monitor patients for adverse effects of alfentanil, such as hypotension, nausea, itching, and respiratory depression. Also, adverse cardiovascular effects, such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered anesthetics, including alfentanil. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after amiodarone discontinuation.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Atorvastatin: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Benazepril: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Celecoxib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Olmesartan: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Valsartan: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Amoxapine: (Major) Consider alternative therapy or reduce the dose of one or both drugs if alfentanil is used with another CNS depressant, such as amoxapine. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Use together with caution. Alfentanil is metabolized by the CYP3A4 isoenzyme. Clarithromycin is an inhibitor of CYP3A4 may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Postmarketing reports of interactions with concomitant use have been noted.
Amphetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with apalutamide is necessary. If apalutamide is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a strong CYP3A4 inducer like apalutamide with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Apomorphine: (Major) Apomorphine may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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) Use caution if alfentanil and aprepitant, fosaprepitant are used concurrently and monitor for an increase in alfentanil-related adverse effects for several days after administration of a multi-day aprepitant regimen. Alfentanil is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of alfentanil. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, when either aprepitant or fosaprepitant are given only as single doses, these drugs only weakly inhibit CYP3A4 and there is no evidence of CYP3A4 induction.
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.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If asciminib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of alfentanil 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 alfentanil 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.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone 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 a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
Atazanavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Atazanavir; Cobicistat: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Atenolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Atenolol; Chlorthalidone: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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.
Atropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of avacopan is necessary. If avacopan is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like avacopan can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If avacopan is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 a thiazide diuretic is administered with alfentanil. 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 alfentanil 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Belladonna; Opium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of belumosudil is necessary. If belumosudil is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like belumosudil can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If belumosudil is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Belzutifan: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with belzutifan is necessary. If belzutifan is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like belzutifan with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Consider alternative therapy or reduce the dose of one or both drugs if alfentanil is used with another CNS depressant such as benzhydrocodone. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia. Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and other opioid agonists 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 methylene blue with alfentanil due to risk of serotonin syndrome or opioid toxicity. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received methylene blue within 14 days. Do not administer alfentanil within 72 hours of the last dose of methylene blue. 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) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of berotralstat is necessary. If berotralstat is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like berotralstat can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If berotralstat is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Beta-blockers: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Betaxolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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.
Bicalutamide: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If bicalutamide is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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.
Bosentan: (Moderate) Drugs that induce cytochrome P450 3A4, including bosentan, may decrease the effectiveness of alfentanil, a substrate for the cytochrome 3A4 isoenzyme. Induction of alfentanil metabolism may take several days.
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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with brigatinib is necessary. If brigatinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Brigatinib is a weak CYP3A inducer. Coadministration of a CYP3A4 inducer like brigatinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers. (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 a loop diuretic is administered with alfentanil. 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 alfentanil. 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 alfentanil. 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: (Moderate) If concomitant use of alfentanil and bupropion 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.
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 alfentanil 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 alfentanil 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. (Moderate) If concomitant use of alfentanil and bupropion 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.
Buspirone: (Moderate) If concomitant use of alfentanil and buspirone 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.
Butalbital; Acetaminophen: (Major) Concomitant use of alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Butorphanol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of capivasertib is necessary. If capivasertib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like capivasertib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If capivasertib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 a thiazide diuretic is administered with alfentanil. 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) Monitor for reduced efficacy of alfentanil and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of alfentanil as needed. If carbamazepine is discontinued, consider a dose reduction of alfentanil and frequently monitor for signs or respiratory depression and sedation. Alfentanil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alfentanil levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbidopa; Levodopa: (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual regimen should be administered as soon as the patient is able to take oral medication.
Carbidopa; Levodopa; Entacapone: (Major) COMT inhibitors may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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. (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual regimen should be administered as soon as the patient is able to take oral medication.
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 alfentanil 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 alfentanil 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Carvedilol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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 alfentanil with cenobamate may cause excessive sedation and somnolence. Limit the use of alfentanil 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, consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with cenobamate is necessary. If cenobamate is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like cenobamate with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Ceritinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ceritinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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.
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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 a thiazide diuretic is administered with alfentanil. 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Chlorthalidone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 alfentanil 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: (Minor) Cimetidine is an inhibitor of CYP3A4 and thus, reduces the clearance of alfentanil and may prolong the duration of action of alfentanil. Smaller alfentanil doses will be needed if prolonged alfentanil administration is used. Monitor patients for adverse effects of alfentanil, such as hypotension, nausea, itching, and respiratory depression.
Ciprofloxacin: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Citalopram: (Moderate) If concomitant use of alfentanil and citalopram 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.
Clarithromycin: (Moderate) Use together with caution. Alfentanil is metabolized by the CYP3A4 isoenzyme. Clarithromycin is an inhibitor of CYP3A4 may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Postmarketing reports of interactions with concomitant use have been noted.
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 alfentanil is coadministered with clevidipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving clevidipine.
Clobazam: (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.
Clofazimine: (Moderate) Monitor for increased toxicity of alfentanil if used concomitantly with clofazimine. Concomitant use may increase the concentration of alfentanil, increasing the risk of adverse effects. Alfentanil is a CYP3A4 substrate that has a narrow therapeutic range; in vitro data suggest clofazimine inhibits CYP3A4.
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 alfentanil, 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) Concomitant use of alfentanil with other CNS depressants, including clozapine, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. Combining alfentanil with clozapine may also lead to additive effects on intestinal motility or bladder function. A dose reduction of one or both drugs may be warranted.
Cobicistat: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Codeine; Promethazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
COMT inhibitors: (Major) COMT inhibitors may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of conivaptan is necessary. If conivaptan is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like conivaptan can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If conivaptan is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Crizotinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of crizotinib is necessary. If crizotinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A inhibitors like crizotinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If crizotinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 alfentanil 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.
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: (Major) The concomitant use of dabrafenib and alfentanil may lead to decreased alfentanil concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of alfentanil efficacy. Dabrafenib is a moderate CYP3A4 inducer and alfentanil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Dalfopristin; Quinupristin: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of dalfopristin; quinupristin is necessary. If dalfopristin; quinupristin is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like dalfopristin; quinupristin can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If dalfopristin; quinupristin is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of drugs metabolized by this enzyme including alfentanil. A dose reduction of one or both drugs may be warranted. Close monitoring for oversedation and respiratory depression is warranted if a CYP3A4 inhibitor is used with alfentanil.
Dantrolene: (Major) Concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of daridorexant is necessary. If daridorexant is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like daridorexant can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If daridorexant is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Darunavir; Cobicistat: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Delavirdine: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like delavirdine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If delavirdine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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.
Desvenlafaxine: (Moderate) If concomitant use of alfentanil and desvenlafaxine 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.
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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with dexamethasone is necessary. If dexamethasone is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like dexamethasone with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (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 alfentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risk 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 alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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; Bupropion: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (Moderate) If concomitant use of alfentanil and bupropion 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.
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. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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; Quinidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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.
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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of diltiazem is necessary. If diltiazem is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like diltiazem can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. Diltiazem increases the half-life of alfentanil by 50% and may delay tracheal extubation after anesthesia. If diltiazem is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) If concomitant use of alfentanil and dolasetron 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.
Dorzolamide; Timolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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) Dronedarone is metabolized by and is an inhibitor of CYP3A. Alfentanil is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
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.
Duloxetine: (Moderate) If concomitant use of alfentanil and duloxetine 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.
Duvelisib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If duvelisib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Echinacea: (Moderate) Alfentanil is a substrate of CYP3A4, and echinacea inhibits intestinal CYP3A4, but induces hepatic CYP3A4. The serum concentration of parenterally administered drugs such as alfentanil may be lowered if administered to patients receiving echinacea. Monitor for changes in efficacy or toxicity when echinacea is coadministered with alfentanil, until more data are available.
Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of other drugs metabolized by this enzyme, such as alfentanil.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of other drugs metabolized by this enzyme, such as alfentanil.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of other drugs metabolized by this enzyme, such as alfentanil.
Elagolix: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with elagolix is necessary. If elagolix is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak to moderate CYP3A4 inducer like elagolix with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with elagolix is necessary. If elagolix is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak to moderate CYP3A4 inducer like elagolix with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Elbasvir; Grazoprevir: (Major) Administering alfentanil with grazoprevir may result in elevated alfentanil plasma concentrations. Alfentanil is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with eletriptan. Inform patients taking this combination of the possible increased risk 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) Use caution when administering ivacaftor and alfentanil concurrently. Ivacaftor is an inhibitor of CYP3A, and alfentanil is a CYP3A substrate. Co-administration can increase alfentanil exposure leading to increased or prolonged therapeutic effects and adverse events.
Eluxadoline: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as alfentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Emapalumab: (Moderate) Monitor for decreased efficacy of alfentanil and adjust the dose as needed during coadministration with emapalumab. Alfentanil is a CYP3A4 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with enasidenib is necessary. If enasidenib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like enasidenib with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Encorafenib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with encorafenib is necessary. If encorafenib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a strong CYP3A inducer like encorafenib with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Entacapone: (Major) COMT inhibitors may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with enzalutamide is necessary. If enzalutamide is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a strong CYP3A4 inducer like enzalutamide with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Eplerenone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when eplerenone is administered with alfentanil. 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.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like erythromycin can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If erythromycin is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Escitalopram: (Moderate) If concomitant use of alfentanil and escitalopram 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.
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.
Esmolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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 a loop diuretic is administered with alfentanil. 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.
Ethotoin: (Moderate) Drugs that induce CYP3A4, including phenytoin or fosphenytoin (and possibly ethotoin), may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome (CYP) 3A4 isoenzyme. Induction of alfentanil metabolism may take several days. In addition, additive CNS depression could be seen with the combined use of the hydantoin and opiate agonists.
Etomidate: (Major) Concomitant use of alfentanil with other CNS depressants can potentiate the effects of alfentanil 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.
Everolimus: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of everolimus is necessary. If everolimus is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like everolimus can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If everolimus is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Fedratinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of fedratinib is necessary. If fedratinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fedratinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If fedratinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Felodipine: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with felodipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of fexinidazole is necessary. If fexinidazole is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like fexinidazole can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If fexinidazole is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Flavoxate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Fluconazole may decrease the systemic clearance of alfentanil. Prolonged duration of opiate action, increased sedation, respiratory depression or other opiate side effects may occur. Close monitoring of patients is warranted.
Fluoxetine: (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme present in the liver. Inhibitors of CYP3A4, such as fluoxetine, may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Close monitoring for oversedation and respiratory depression is warranted if a CYP3A4 inhibitor is used with alfentanil.
Fluphenazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. 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: (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme. Inhibitors of CYP3A4, such as fluvoxamine, may decrease systemic clearance of alfentanil leading to increased or prolonged effects.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Drugs that induce CYP3A4, including phenytoin or fosphenytoin (and possibly ethotoin), may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome (CYP) 3A4 isoenzyme. Induction of alfentanil metabolism may take several days. In addition, additive CNS depression could be seen with the combined use of the hydantoin and opiate agonists.
Fostamatinib: (Moderate) Monitor for alfentanil toxicities that may require alfentanil dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a sensitive CYP3A4 substrate may increase the concentration of the CYP3A4 substrate. The active metabolite of fostamatinib, R406, is a CYP3A4 inhibitor; alfentanil is a sensitive substrate for CYP3A4. Coadministration of fostamatinib with another sensitive CYP3A4 substrate increased the substrate AUC by 64% and Cmax by 113%.
Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with frovatriptan. Inform patients taking this combination of the possible increased risk 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 a loop diuretic is administered with alfentanil. 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 alfentanil 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 magnitude and duration of CNS and cardiovascular effects of alfentanil may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Glycerol Phenylbutyrate: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with glycerol phenylbutyrate is necessary. If glycerol phenylbutyrate is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like glycerol phenylbutyrate with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) If concomitant use of alfentanil and granisetron 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.
Guaifenesin; 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.
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: (Minor) Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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.
Hydantoins: (Moderate) Drugs that induce CYP3A4, including phenytoin or fosphenytoin (and possibly ethotoin), may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome (CYP) 3A4 isoenzyme. Induction of alfentanil metabolism may take several days. In addition, additive CNS depression could be seen with the combined use of the hydantoin and opiate agonists.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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.
Hydrocodone; Pseudoephedrine: (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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 methylene blue with alfentanil due to risk of serotonin syndrome or opioid toxicity. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received methylene blue within 14 days. Do not administer alfentanil within 72 hours of the last dose of methylene blue. 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) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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.
Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone 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 a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with alfentanil, a CYP3A substrate, as alfentanil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
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) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme present in the liver. Inhibitors of CYP3A4, such as imatinib, may decrease systemic clearance of alfentanil leading to increased or prolonged effects.
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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 afentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Concomitant use of isavuconazonium with alfentanil may result in increased serum concentrations of alfentanil. Alfentanil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Major) The use of alfentanil 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: (Major) Concomitant use of alfentanil with other CNS depressants can potentiate the effects of alfentanil on respiration, CNS depression, sedation, and hypotension. Both the magnitude and duration of CNS and cardiovascular effects may be enhanced with concurrent alfentanil and inhalation general anesthetics.
Isoniazid, INH: (Major) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression, sedation, serotonin syndrome and hypertension if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Isoniazid has MAOI activity. Severe and unpredictable potentiation of MAOIs has been reported rarely with alfentanil. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Monitor for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension if alfentanil is administered to patients who have received MAO inhibitors within 14 days. In addition, alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If isoniazid is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression, sedation, serotonin syndrome and hypertension if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Isoniazid has MAOI activity. Severe and unpredictable potentiation of MAOIs has been reported rarely with alfentanil. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Monitor for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension if alfentanil is administered to patients who have received MAO inhibitors within 14 days. In addition, alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If isoniazid is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Isoniazid, INH; Rifampin: (Major) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression, sedation, serotonin syndrome and hypertension if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Isoniazid has MAOI activity. Severe and unpredictable potentiation of MAOIs has been reported rarely with alfentanil. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Monitor for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension if alfentanil is administered to patients who have received MAO inhibitors within 14 days. In addition, alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If isoniazid is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Isradipine: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with isradipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving isradipine.
Istradefylline: (Moderate) Consider a reduced dose of alfentanil 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 alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. Coadministration can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If istradefylline is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of itraconazole is necessary. If itraconazole is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like itraconazole can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If itraconazole is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Ivacaftor: (Moderate) Use caution when administering ivacaftor and alfentanil concurrently. Ivacaftor is an inhibitor of CYP3A, and alfentanil is a CYP3A substrate. Co-administration can increase alfentanil exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivosidenib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with ivosidenib is necessary. If ivosidenib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like ivosidenib with alfentanil, a sensitive CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Ketamine: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ketoconazole is necessary. If ketoconazole is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ketoconazole can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ketoconazole is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Labetalol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Use together with caution. Alfentanil is metabolized by the CYP3A4 isoenzyme. Clarithromycin is an inhibitor of CYP3A4 may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Postmarketing reports of interactions with concomitant use have been noted.
Lapatinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of lapatinib is necessary. If lapatinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like lapatinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If lapatinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Larotrectinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of larotrectinib is necessary. If larotrectinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like larotrectinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If larotrectinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Lasmiditan: (Moderate) Concomitant use of alfentanil with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of oral lefamulin is necessary. If oral lefamulin is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like oral lefamulin can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. An interaction is not expected with intravenous lefamulin. If oral lefamulin is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Lemborexant: (Moderate) Concomitant use of alfenatanil with lemborexant may cause excessive sedation and somnolence. Limit the use of alfenatanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of lenacapavir is necessary. If lenacapavir is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like lenacapavir can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If lenacapavir is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Letermovir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of letermovir is necessary; the magnitude of this interaction may be amplified if the patient is also receiving cyclosporine. If letermovir is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like letermovir can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If letermovir is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Levamlodipine: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Levobunolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is 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.
Levodopa: (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual regimen should be administered as soon as the patient is able to take oral medication.
Levoketoconazole: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ketoconazole is necessary. If ketoconazole is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ketoconazole can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ketoconazole is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Levomilnacipran: (Moderate) If concomitant use of alfentanil 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 alfentanil in patients receiving linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If coadministration or administration of alfentanil within 14 days of linezolid is warranted, monitor patients for hypertension and serotonin syndrome. Ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lisdexamfetamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 a thiazide diuretic is administered with alfentanil. 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 alfentanil 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 alfentanil. Lofexidine can potentiate the effects of CNS depressants.
Lonafarnib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of lonafarnib is necessary. If lonafarnib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like lonafarnib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If lonafarnib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Loop diuretics: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a loop diuretic is administered with alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with lorlatinib is necessary. If lorlatinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like lorlatinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 alfentanil, 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) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of alfentanil. If used together, alfentanil dosages may need to be adjusted. Alfentanil is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. In a crossover study in healthy males, plasma alfentanil concentration-time profiles significantly depended on CYP3A4 activity. In the presence of rifampin, another strong CYP3A inducer, alfentanil noncompartmental clearance increased from 5.3 +/- 2.3 mL/kg/minute to 14.6 +/- 3.8 mL/kg/minute and elimination half-life decreased from 58 +/- 13 minutes to 35 +/- 7 minutes. (Moderate) Use caution when administering ivacaftor and alfentanil concurrently. Ivacaftor is an inhibitor of CYP3A, and alfentanil is a CYP3A substrate. Co-administration can increase alfentanil exposure leading to increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of alfentanil. If used together, alfentanil dosages may need to be adjusted. Alfentanil is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. In a crossover study in healthy males, plasma alfentanil concentration-time profiles significantly depended on CYP3A4 activity. In the presence of rifampin, another strong CYP3A inducer, alfentanil noncompartmental clearance increased from 5.3 +/- 2.3 mL/kg/minute to 14.6 +/- 3.8 mL/kg/minute and elimination half-life decreased from 58 +/- 13 minutes to 35 +/- 7 minutes.
Lumateperone: (Moderate) Concomitant use of opioid agonists like alfentanil 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 alfentanil 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) Consider alternative therapy or reduce the dose of one or both drugs if alfentanil is used with another CNS depressant, such as maprotiline. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia.
Maribavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of maribavir is necessary. If maribavir is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like maribavir can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If maribavir is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Mavacamten: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with mavacamten is necessary. If mavacamten is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A inducer like mavacamten with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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 alfentanil with meprobamate can potentiate the effects of alfentanil 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 alfentanil may also be augmented. Dose reductions of one or both drugs may be needed.
Meropenem: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with meropenem is necessary. If meropenem is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like meropenem with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Meropenem; Vaborbactam: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with meropenem is necessary. If meropenem is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like meropenem with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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 alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk 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 methylene blue with alfentanil due to risk of serotonin syndrome or opioid toxicity. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received methylene blue within 14 days. Do not administer alfentanil within 72 hours of the last dose of methylene blue. 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) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Methscopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 methylene blue with alfentanil due to risk of serotonin syndrome or opioid toxicity. If cannot avoid use, choose the lowest possible methylene blue dose and observe the patient closely for up to 4 hours after administration. Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received methylene blue within 14 days. Do not administer alfentanil within 72 hours of the last dose of methylene blue. 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.
Methylphenidate Derivatives: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risk 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 alfentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risk 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 a thiazide diuretic is administered with alfentanil. 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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.
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: (Major) Coadministration of alfentanil is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome or other hormonal conditions. Mifepristone inhibits CYP3A4. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, such as alfentanil. The increase in alfentanil concentrations can increase the risk for serious CNS depression and respiratory depression, particularly when mifepristone is added after a stable dose of alfentanil is achieved. A reduced dosage of alfentanil may be necessary if use together is not avoidable. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Milnacipran: (Moderate) If concomitant use of alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with mitapivat is necessary. If mitapivat is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like mitapivat with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Mitotane: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with mitotane is necessary. If mitotane is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like mitotane with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Mobocertinib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with mobocertinib is necessary. If mobocertinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like mobocertinib with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Molindone: (Moderate) Concomitant use of opioid agonists like alfentanil 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 alfentanil 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: (Major) Concomitant use of morphine with alfentanil can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. If alfentanil is used concurrently with morphine, monitor patients for sedation and respiratory depression.
Morphine; Naltrexone: (Major) Concomitant use of morphine with alfentanil can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. If alfentanil is used concurrently with morphine, monitor patients for sedation and respiratory depression.
Nabilone: (Major) Avoid coadministration of opioid agonists with nabilone due to the risk of additive CNS depression.
Nadolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Nalbuphine: (Major) Avoid the concomitant use of nalbuphine and opiate agonists, such as alfentanil. 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 alfentanil 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 alfentanil 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 alfentanil with naratriptan. Inform patients taking this combination of the possible increased risk 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Nebivolol; Valsartan: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Nefazodone: (Moderate) Certain opiate agonists, such as alfentanil, are metabolized via cytochrome P450 3A4. Nefazodone inhibits the metabolism of these agents and may lead to excessive opiate agonist effects.
Nelfinavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Neostigmine; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) If concomitant use of alfentanil and palonosetron 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.
Nevirapine: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with nevirapine is necessary. If nevirapine is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like nevirapine with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Nicardipine: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of nicardipine is necessary. If nicardipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like nicardipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If nicardipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
NIFEdipine: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with nifedipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving nifedipine.
Nilotinib: (Major) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and alfentanil, a CYP3A4 substrate with a narrow therapeutic range, may result in increased alfentanil levels. Monitor for oversedation, respiratory depression, and hypotension. An alfentanil dose reduction may be necessary if these drugs are used together.
Nimodipine: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with nimodipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving nimodipine.
Nirmatrelvir; Ritonavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Nirogacestat: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of nirogacestat is necessary. If nirogacestat is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like nirogacestat can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If nirogacestat is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Nisoldipine: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with nisoldipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with odevixibat is necessary. If odevixibat is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like odevixibat with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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) 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. (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme present in the liver. Inhibitors of CYP3A4, such as fluoxetine, may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Close monitoring for oversedation and respiratory depression is warranted if a CYP3A4 inhibitor is used with alfentanil.
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 alfentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with olutasidenib is necessary. If olutasidenib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like olutasidenib with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Omaveloxolone: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with omaveloxolone is necessary. If omaveloxolone is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like omaveloxolone with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Ondansetron: (Moderate) If concomitant use of alfentanil and ondansetron 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.
Opicapone: (Major) COMT inhibitors may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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) Alfentanil is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of alfentanil may be reduced if these drugs are administered concurrently.
Orphenadrine: (Major) Concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of osilodrostat is necessary. If osilodrostat is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like osilodrostat can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If osilodrostat is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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) Drugs that induce cytochrome P450 3A4, including oxcarbazepine, may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome 3A4 isoenzyme. Induction of alfentanil metabolism may take several days.
Oxybutynin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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.
Oxycodone: (Major) Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone 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 a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
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 alfentanil 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 alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If pacritinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Palbociclib: (Moderate) Monitor patients for respiratory depression and sedation at frequent intervals if coadministration with palbociclib is necessary. The dose of alfentanil may need to be reduced. This interaction is most likely to occur if palbociclib is added after a stable dose of alfentanil is achieved. Palbociclib is a weak time-dependent inhibitor of CYP3A while alfentanil is a sensitive CYP3A4 substrate with narrow therapeutic range.
Paliperidone: (Moderate) Drugs that can cause CNS depression such as alfentanil, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Palonosetron: (Moderate) If concomitant use of alfentanil and palonosetron 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.
Paroxetine: (Moderate) If concomitant use of alfentanil 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) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and alfentanil, a CYP3A4 substrate, may cause an increase in systemic concentrations of alfentanil. Use caution when administering these drugs concomitantly.
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: (Major) Avoid the concomitant use of pentazocine and opiate agonists, such as alfentanil. 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.
Pentazocine; Naloxone: (Major) Avoid the concomitant use of pentazocine and opiate agonists, such as alfentanil. 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Perphenazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. 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) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Pexidartinib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with pexidartinib is necessary. If pexidartinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like pexidartinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Phenelzine: (Major) The use of alfentanil 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Phenytoin: (Moderate) Drugs that induce CYP3A4, including phenytoin or fosphenytoin (and possibly ethotoin), may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome (CYP) 3A4 isoenzyme. Induction of alfentanil metabolism may take several days. In addition, additive CNS depression could be seen with the combined use of the hydantoin and opiate agonists.
Pimozide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including opiate agonists.
Pindolol: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Pirtobrutinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of pirtobrutinib is necessary. If pirtobrutinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like pirtobrutinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil.
Posaconazole: (Moderate) Posaconazole and alfentanil should be coadministered with caution due to an increased potential for alfentanil-related adverse events and prolonged effects. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of alfentanil. These drugs used in combination may result in elevated alfentanil plasma concentrations, causing an increased risk for alfentanil-related adverse events.
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 alfentanil 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 magnitude and duration of CNS and cardiovascular effects of alfentanil may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia. 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Procarbazine: (Major) In theory, the use of alfentanil in a patient taking procarbazine may increase the risk of serotonergic symptoms. Procarbazine has MAOI activity; the manufacturer of alfentanil does not recommend its use within 14 days of an MAO Inhibitor. Alfentanil belongs to the same group of opiate agonists, phenylpiperidines, as meperidine, a known serotonin reuptake inhibitor. Caution is advised until more data are available.
Prochlorperazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Promethazine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Promethazine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk 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. (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Promethazine; Phenylephrine: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Protease inhibitors: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 a thiazide diuretic is administered with alfentanil. 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.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ranolazine is necessary. If ranolazine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ranolazine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ranolazine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Rasagiline: (Moderate) Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received rasagiline within 14 days. Rasagiline interactions with alfentanil may also manifest as opioid toxicity. 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.
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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with repotrectinib is necessary. If repotrectinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A inducer like repotrectinib with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Ribociclib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ribociclib is necessary. If ribociclib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ribociclib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ribociclib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Ribociclib; Letrozole: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ribociclib is necessary. If ribociclib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ribociclib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ribociclib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Rifabutin: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Rifampin: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Rifamycins: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Rifapentine: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Risperidone: (Moderate) Due to the sedative effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications including opiate agonists such as alfentanil.
Ritlecitinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ritlecitinib is necessary. If ritlecitinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like ritlecitinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ritlecitinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Ritonavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with rizatriptan. Inform patients taking this combination of the possible increased risk 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of rucaparib is necessary. If rucaparib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor. Coadministration can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If rucaparib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Sarilumab: (Moderate) Monitor for evidence of reduced effect if alfentanil coadministration with sarilumab is necessary; alfentanil dosage adjustment may be needed. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as alfentanil, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Alfentanil is a CYP3A4 substrate and a narrow therapeutic index drug.
Scopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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 alfentanil with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate 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. Additionally, concurrent use of alfentanil with a barbiturate may decrease alfentanil 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 a barbiturate may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Barbiturates induce CYP3A4; alfentanil is a CYP3A4 substrate.
Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking alfentanil, monitor for altered patient response to alfentanil; alfentanil dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as alfentanil.
Selegiline: (Moderate) Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received selegiline within 14 days. Selegiline interactions with alfentanil may also manifest as opioid toxicity. 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.
Selpercatinib: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of selpercatinib is necessary. If selpercatinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like selpercatinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If selpercatinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risk 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 alfentanil 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) Concurrent use of sevoflurane with opiate agonists such as alfentanil can reduce the minimal alveolar concentration (MAC) and increase the CNS depression, hypotension, and respiratory depression associated with sevoflurane administration. Postoperative respiratory depression associated with alfentanil may also be augmented. If alfentanil is used with one of these drugs, the dose of one or both agents may need to be reduced. Requirements for volatile inhalation anesthetics or alfentanil infusion are reduced by 30% to 50% for the first hour of maintenance following an anesthetic induction dose of alfentanil. Discontinue alfentanil infusions at least 10 to 15 minutes before the end of surgery during general anesthesia.
Siltuximab: (Moderate) Monitor for evidence of reduced effect if alfentanil coadministration with siltuximab is necessary; alfentanil dosage adjustment may be needed. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as alfentanil, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Alfentanil is a CYP3A4 substrate and a narrow therapeutic index drug.
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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with taurursodiol is necessary. If taurursodiol is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like taurursodiol with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Solifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of alfentanil 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Sotorasib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with sotorasib is necessary. If sotorasib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like sotorasib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Spironolactone: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If spironolactone is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If spironolactone is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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) St. John's wort (Hypericum perforatum) may increase the risk for serotonin syndrome when combined with alfentanil, and may also intensify or prolong the effects of general anesthetics. The onset of serotonergic symptoms generally occurs within several hours to a few days of concomitant use, but may occur later. Monitor the patient closely if use of St. John's Wort is reported pre-operatively. In one report, the authors recommend that patients should discontinue taking St. John's Wort at least 5 days prior to anesthesia. The American Society of Anesthesiologists has recommended that, if possible, patients should stop taking herbal medications at least 2 to 3 weeks before surgery to decrease the risk of adverse reactions. If use together is necessary and serotonin syndrome is suspected, discontinue alfentanil.
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 alfentanil resulting in an increased risk of adverse reactions and/or decreased efficacy. Alfentanil is a sensitive substrate of CYP3A4. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of dalfopristin; quinupristin is necessary. If dalfopristin; quinupristin is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like dalfopristin; quinupristin can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If dalfopristin; quinupristin is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with sumatriptan. Inform patients taking this combination of the possible increased risk 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 alfentanil with sumatriptan. Inform patients taking this combination of the possible increased risk 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 alfentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of tapentadol with alfentanil 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with tazemetostat is necessary. If tazemetostat is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like tazemetostat with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Tedizolid: (Moderate) Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received tedizolid within 14 days. Tedizolid interactions with alfentanil may also manifest as opioid toxicity. 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.
Telmisartan; Amlodipine: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of amlodipine is necessary. If amlodipine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like amlodipine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If amlodipine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. 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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with telotristat is necessary. If telotristat is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like telotristat with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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 all local anesthetics, they should be used with caution with other agents that can cause respiratory depression including opiate agonists like alfentanil. 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) Use caution when administering ivacaftor and alfentanil concurrently. Ivacaftor is an inhibitor of CYP3A, and alfentanil is a CYP3A substrate. Co-administration can increase alfentanil exposure leading to increased or prolonged therapeutic effects and adverse events.
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 a thiazide diuretic is administered with alfentanil. 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) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Thiothixene: (Moderate) Concomitant use of opioid agonists like alfentanil 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 alfentanil, 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) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Tipranavir: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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.
Tocilizumab: (Moderate) Monitor for evidence of reduced effect if alfentanil coadministration with tocilizumab is necessary; alfentanil dosage adjustment may be needed. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as alfentanil, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Alfentanil is a CYP3A4 substrate and narrow therapeutic index drug.
Tolcapone: (Major) COMT inhibitors may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil 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 alfentanil is used concomitantly with an anticholinergic drug, such as tolterodine. The concomitant use of alfentanil 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.
Torsemide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a loop diuretic is administered with alfentanil. 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of verapamil is necessary. If verapamil is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like verapamil can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If verapamil is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Tranylcypromine: (Major) The use of alfentanil 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 alifentanil 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 alfentanil. 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 a thiazide diuretic is administered with alfentanil. 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 alfentanil. 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) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. 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 alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of trofinetide is necessary. If trofinetide is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like trofinetide can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If trofinetide is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of tucatinib is necessary. If tucatinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like tucatinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If tucatinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 a thiazide diuretic is administered with alfentanil. 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, like alfentanil, 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 alfentanil, could be expected with concurrent use. Use caution, and monitor therapeutic effects of alfentanil when coadministered with vemurafenib.
Venlafaxine: (Moderate) If concomitant use of alfentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of verapamil is necessary. If verapamil is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like verapamil can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If verapamil is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
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 alifentanil 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of viloxazine is necessary. If viloxazine is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like viloxazine can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If viloxazine is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Vonoprazan: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like vonoprazan can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If vonoprazan is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Vonoprazan; Amoxicillin: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like vonoprazan can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If vonoprazan is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of vonoprazan is necessary. If vonoprazan is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like vonoprazan can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If vonoprazan is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Use together with caution. Alfentanil is metabolized by the CYP3A4 isoenzyme. Clarithromycin is an inhibitor of CYP3A4 may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Postmarketing reports of interactions with concomitant use have been noted.
Voriconazole: (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme. Agents that inhibit CYP3A4 activity, such as voriconazole, may decrease systemic clearance of alfentanil leading to increased or prolonged effects.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with vortioxetine. Inform patients taking this combination of the possible increased risk 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) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of voxelotor is necessary. If voxelotor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like voxelotor can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If voxelotor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Zafirlukast: (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme. Drugs that inhibit CYP3A4, such as zafirlukast, may decrease systemic clearance of alfentanil leading to increased or prolonged effects. Close monitoring for oversedation and respiratory depression is warranted if a CYP3A4 inhibitor is used with alfentanil.
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.
Zanubrutinib: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with zanubrutinib is necessary. If zanubrutinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like zanubrutinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory 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 alfentanil 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 alfentanil with zolmitriptan. Inform patients taking this combination of the possible increased risk 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: (Moderate) 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.
Alfentanil is a strong agonist at primarily u- and kappa- opiate receptors. Opiate receptors are coupled with G-protein (guanine-nucleotide-binding protein) receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Opioid-G-protein systems include adenylyl cyclase-cyclic adenosine monophosphate (cAMP) and phospholipase3 C (PLC)-intositol 1,4,5 triphosphate (Ins(1,4,5)P3)-Ca2). Opiates do not alter the pain threshold of afferent nerve endings to noxious stimuli, nor do they affect the conductance of impulses along peripheral nerves. Analgesia is mediated through changes in the perception of pain at the spinal cord (u2-, delta-, kappa-receptors) and higher levels in the CNS (u1- and kappa3 receptors). There is no ceiling effect of analgesia for opiates. The emotional response to pain is also altered. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (u and delta receptor agonist) resulting in hyperpolarization and reduced neuronal excitability. Binding of the opiate stimulates the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the G-protein complex. Binding of GTP leads to a release of the G-protein subunit, which acts on the effector system. In this case of opioid-induced analgesia, the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane. Thus, opioids decrease intracellular cAMP by inhibiting adenylate cyclase that modulates the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and norepinephrine. Opioids also modulate the endocrine and immune systems. Opioids inhibit the release of vasopressin, somatostatin, insulin and glucagon.
The actions of alfentanil are similar to those of fentanyl, although alfentanil is less lipophilic than fentanyl. Alfentanil is more lipophilic than morphine (100:1). Alfentanil has a more rapid onset of action than fentanyl, sufentanil, and morphine. Clinically, stimulation of u-receptors produces analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, and physical dependence. Kappa-receptor stimulation also produces analgesia, miosis, respiratory depression, dysphoria and some psychomimetic effects (i.e., disorientation and/or depersonalization). Miosis is produced by an excitatory action on the autonomic segment of the nucleus of the oculomotor nerve. Opiate-induced respiratory depression is caused by direct action on respiratory centers in the brain stem. Recovery from respiratory depression following surgery is more rapid with alfentanil than morphine or fentanyl due to a shorter half-life and reduced accumulation in tissues. Opiate agonists increase smooth muscle tone in the antral portion of the stomach, the small intestine (especially the duodenum), the large intestine, and the sphincters. Opiate agonists also decrease secretions from the stomach, pancreas, and biliary tract. The combination of effects of opiate agonists on the GI tract results in constipation and delayed digestion. Urinary smooth muscle tone is also increased by opiate agonists. The tone of the bladder detrusor muscle, ureters, and vesical sphincter is increased, which sometimes causes urinary retention. Alfentanil rarely stimulates the release of histamine. Bradycardia is due to medullary vasomotor center depression and vagal nucleus stimulation and may lead to decreased cardiac output. Myocardial contractility is not affected by alfentanil. Muscle rigidity of the chest and abdominal muscles is often seen with opiate agonist anesthesia. This effect may be due to opiate stimulation of spinal reflexes or interference with basal ganglia integration. When used as part of anesthesia, opiate agonists provide analgesic protection against hemodynamic responses to surgical stress by attenuating the catecholamine response.
Alfentanil is administered intravenously or epidurally. It undergoes liver biotransformation via cytochrome P450 isoenzyme 3A4. Alfentanil metabolites are excreted in the urine; less than 1% is excreted unchanged. The terminal half-life is 90-111 minutes.
Affected cytochrome P450 isoenzymes: CYP3A4
Alfentanil is metabolized by the CYP3A4 isoenzyme.
-Route-Specific Pharmacokinetics
Intravenous Route
The onset of action of alfentanil is immediate after intravenous administration. Alfentanil has a volume of distribution that is one-fourth to one-tenth that of fentanyl. Alfentanil is has a stronger affinity for plasma proteins than tissue proteins, which may explain its smaller volume of distribution. Alfentanil is strongly bound to alpha1-acid glycoprotein, and the free fraction of alfentanil is directly related to the concentration of this protein. At serum concentrations of 0.4-100 ng/mL, alfentanil is 88-92% protein bound while at higher serum concentrations (10-100 mcg/mL), alfentanil is < 60% protein bound due to saturation of binding sites. Disease states that decrease the concentration of serum alpha1-acid glycoprotein may lead to an increased effect of alfentanil. During cardiopulmonary bypass procedures, the volume of distribution, elimination half-life, and free fraction of alfentanil increase by a factor of 2-4. These changes are due to changes in the serum concentration of alpha1-acid glycoprotein. A three-compartment model explains the distribution and elimination of alfentanil. Alfentanil distribution half-lives are 1 and 14 minutes, and the terminal half-life is 90-111 minutes.
In patients receiving alfentanil with nitrous oxide/oxygen for anesthesia, alfentanil plasma concentrations of 310-340 ng/mL provides adequate anesthesia for intra-abdominal surgery. Serum concentrations of 190 ng/mL block the response to skin closure, and serum concentrations of 100-200 ng/mL produce sufficient anesthesia for superficial surgery. At alfentanil doses of 150 mcg/kg IV, hypnosis is seen. The anesthetic ED90 of alfentanil is 182 mcg/kg IV in non-premedicated patients.
-Special Populations
Hepatic Impairment
Patients with liver dysfunction tend to have a decreased clearance of alfentanil, which leads to prolonged recovery times after surgery. These patients are particularly susceptible to accumulation of alfentanil with repeated dosing.
Renal Impairment
Dosage adjustments for alfentanil are not required in patients with renal dysfunction.
Geriatric
The elderly tend to have a decreased clearance of alfentanil, which leads to prolonged recovery times after surgery. These patients are particularly susceptible to accumulation of alfentanil with repeated dosing.