Oliceridine is an intravenous opioid agonist indicated for the treatment of severe acute pain in adults, where the pain is severe enough to require an intravenous opioid and for whom alternative treatments are inadequate. Oliceridine is indicated for use in hospitals or other controlled clinical settings, such as during inpatient and outpatient procedures. It is not indicated for at-home use. Use of oliceridine beyond 48 hours has not been evaluated in controlled clinical trials. Safety and efficacy were established by comparing oliceridine to both morphine and placebo in randomized, controlled trials of patients undergoing bunionectomy (n = 389) or abdominoplasty (n = 401). Oliceridine demonstrated a statistically greater reduction in pain intensity than placebo and was non-inferior to morphine in both populations. It has a favorable safety and tolerability profile for respiratory and gastrointestinal adverse effects compared to morphine.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Oliceridine is a clear, colorless solution. Do not use if visibly opaque particles, discoloration, or other foreign particles are observed.
-Monitor patients closely for respiratory depression, especially within the first 24 to 48 hours after initiation and dose escalation.
Intravenous Administration
Intermittent IV Injection
-Administer undiluted.
Patient-Controlled Analgesia (PCA)
-The 30 mg/30 mL vial is intended for patient-controlled analgesia (PCA) use only.
-Draw oliceridine directly from the vial into the PCA syringe or bag without diluting.
Serious, life-threatening, or fatal respiratory depression can occur with oliceridine use. Hypoxia (5% to 20%) was among the most common adverse reactions during oliceridine clinical trials; hypoventilation, decreased oxygen saturation (more than 1% to 5%), cough (more than 1% to less than 5%), dyspnea (more than 1% to less than 5%) were also reported.
Dizziness (9% to 35%) and headache (more than 1% to 26%) were among the most common adverse reactions during oliceridine clinical trials; drowsiness (0% to 19%) and sedation (4% to 14%) have also been reported. Anxiety, insomnia, and restlessness were reported in more than 1% to less than 5% of oliceridine-treated patients during clinical trials. Oliceridine may increase the frequency of seizures in patients with seizure disorders and may also increase the risk of seizures occurring in other clinical settings associated with seizures.
Oliceridine may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Hypotension, sinus tachycardia, increased blood pressure, and flushing were reported in more than 1% to less than 5% of oliceridine-treated patients during clinical trials; hot flush was reported in more than 1% to 7% of patients.
Nausea (29% to 75%), vomiting (9% to 43%), and constipation (10% to 17%) were among the most common adverse reactions during oliceridine clinical trials. Flatulence, xerostomia, dyspepsia, diarrhea, and procedural nausea were reported in more than 1% to less than 5% of patients. Like other opioids, oliceridine may cause spasm of the sphincter of Oddi and increases in serum amylase.
Elevated hepatic enzymes (increased ALT and AST) were reported in more than 1% to less than 5% of oliceridine-treated patients during clinical trials.
Opioids may 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 use of opioids 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.
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.
Pruritus (more than 1% to 17%) was among the most common adverse reactions during oliceridine clinical trials; urticaria, hyperhidrosis (more than 1% to less than 5%), and rash (more than 1% to less than 5%) have also been reported.
Back pain (4% to 13%) and muscle cramps/spasms (more than 1% to less than 5%) were reported in oliceridine-treated patients during clinical trials.
Hypokalemia, hypocalcemia, hypophosphatemia, and hypomagnesemia were reported in more than 1% to less than 5% of oliceridine-treated patients during clinical trials.
Fever and extravasation were reported in more than 1% to less than 5% of oliceridine-treated patients during clinical trials.
Pharmacologic tolerance can develop during chronic opioid therapy. Tolerance is the need for increasing opioid doses to maintain initial pain relief. Typically, tolerance presents as a decrease in the duration of analgesia and can be managed by increasing the opioid dose or frequency. There is no limit to tolerance, thus some patients may require very large doses of opioid analgesics to control their pain. When increasing doses of analgesia are required, causes may be multi-factorial including tolerance, progression of disease, or psychologic distress.
Oliceridine is a controlled substance with a high potential for abuse and psychological dependence. Abuse and addiction are separate and distinct from physiological dependence and tolerance, which can develop during chronic opioid therapy. Tolerance is characterized by a reduced response to a drug after repeated administration. Physiological dependence develops as a result of repeated drug use. It manifests with a withdrawal syndrome after abrupt discontinuation or significant dose reduction, or administration of an agent with opioid antagonist activity (e.g., naloxone). Withdrawal is characterized by restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms include irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal. Neonatal opioid withdrawal syndrome may be life-threatening and requires management according to protocols developed by neonatology experts. It presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.
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.
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.
Oliceridine is contraindicated in patients with a known hypersensitivity to oliceridine.
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.
Oliceridine is contraindicated in patients with significant respiratory depression and those with acute or severe asthma in an unmonitored setting or in the absence of resuscitative equipment. Avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective dosages and minimum treatment durations needed. Monitor patients closely for signs or symptoms of respiratory depression and sedation. Patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, respiratory insufficiency, hypoxemia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive even at recommended doses. Patients with advanced age, cachexia, or debilitation are also at an increased risk for opioid-induced respiratory depression. Monitor such patients closely, particularly when initiating and titrating the opioid; consider the use of non-opioid analgesics in these patients. Opioids increase the risk of central sleep apnea (CSA) and sleep-related hypoxemia in a dose-dependent fashion. Consider decreasing the opioid dosage in patients with CSA. Respiratory depression, if left untreated, may cause respiratory arrest and death. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring and dose titration is required, particularly when CYP3A4 and/or CYP2D6 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 and/or CYP2D6 inhibitor or discontinuation of a concurrently used CYP3A4 and/or CYP2D6 inducer may increase plasma oliceridine concentrations and potentiate the risk of fatal respiratory depression. Management of respiratory depression may include observation, necessary supportive measures, and opioid antagonist use when indicated.
Oliceridine is contraindicated in patients with known or suspected GI obstruction, including paralytic ileus. Oliceridine may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Use oliceridine with caution in geriatric adults, starting at the low end of the dosing range and titrating slowly. Monitor for signs of central nervous system and respiratory depression. Geriatric individuals may have increased sensitivity to oliceridine, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy. According to the Beers Criteria, opioids are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures; avoid in these patient populations, except in the setting of severe acute pain, since opioids can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opioid must be used, consider reducing the use of other medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.
Avoid abrupt discontinuation of oliceridine in a physically-dependent patient. When a patient who has been taking opioids regularly and may be physically dependent no longer requires therapy with oliceridine, taper the dose gradually while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Consider tapering to reduced opioid dosage, or tapering and discontinuing long-term opioid therapy, when pain improves; the patient requests dosage reduction or discontinuation; pain and function are not meaningfully improved; the patient is receiving higher opioid doses without evidence of benefit from the higher dose; the patient has current evidence of opioid misuse; the patient experiences side effects that diminish quality of life or impair function; the patient experiences an overdose or other serious event (e.g., hospitalization, injury) or has warning signs for an impending event such as confusion, sedation, or slurred speech; the patient is receiving medications (e.g., benzodiazepines) or has medical conditions (e.g., lung disease, sleep apnea, liver disease, kidney disease, fall risk, advanced age) that increase risk for adverse outcomes; or the patient has been treated with opioids for a prolonged period and current benefit-harm balance is unclear. If the patient has a serious mental illness, is at high suicide risk, or has suicidal ideation, offer or arrange for consultation with a behavioral health provider before initiating a taper. In patients with opioid use disorder, offer or arrange for medication-assisted treatment. Individualize opioid tapering schedules. The longer the duration of previous opioid therapy, the longer the taper may take. Common tapers involve dose reduction of 5% to 20% every 4 weeks; a faster taper may be appropriate for some patients. Significant opioid withdrawal symptoms may indicate the need to pause or slow the taper. Opioids may be stopped, if appropriate, when taken less often than once daily. Advise patients that there is an increased risk for overdose on abrupt return to a previously prescribed higher dose; provide opioid overdose education, and consider offering naloxone. Monitor patients closely for anxiety, depression, suicidal ideation, and opioid use disorder, and offer support and referral as needed.
Avoid oliceridine use in patients with CNS depression, impaired consciousness, or coma; opioids may obscure the clinical course in a patient with a head trauma injury. Monitor patients who may be susceptible to the intracranial effect of carbon dioxide retention (e.g., those with evidence of increased intracranial pressure, brain tumor, or intracranial mass) for signs of sedation and respiratory depression, particularly when initiating oliceridine therapy. Oliceridine may reduce respiratory drive and resultant carbon dioxide retention can further increase intracranial pressure.
Warn patients against performing potentially hazardous activities such as driving or operating machinery unless they are tolerant to the effects of oliceridine and know how they will react to the medication. Oliceridine may impair mental or physical abilities required to perform such tasks.
Oliceridine may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by hypovolemia or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines, general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the opioid dosage. Avoid the use of oliceridine in patients with circulatory shock; it may cause vasodilation that can further reduce cardiac output and blood pressure.
Monitor patients with a history of seizure disorder for worsened seizure control during oliceridine therapy. Oliceridine may increase the frequency of seizures in patients with preexisting seizure disorders and may also increase the risk of seizures occurring in other clinical settings associated with seizures.
Patients with mild or moderate hepatic disease may require less frequent oliceridine dosing. When using oliceridine in patients with severe hepatic disease, consider reducing the initial dose, and administer subsequent doses only after a careful review of the patient's severity of pain and overall clinical status.
Dose-dependent QT prolongation was observed during dedicated QT/QTc studies; the underlying mechanism and clinical significance of the transient QT changes seen in healthy volunteers are unknown. Do not exceed a cumulative total daily dose of 27 mg. Use oliceridine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause an electrolyte imbalance. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.
Patients who are CYP2D6 poor metabolizers may require less frequent oliceridine dosing. Closely monitor these patients for respiratory depression and sedation at frequent intervals and base subsequent dosing on the patient's severity of pain and response to treatment.
There are no available data on the use of oliceridine during human pregnancy to evaluate for a drug-associated risk of birth defects and miscarriage. Oliceridine 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. 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. Guidelines recommend early universal screening of pregnant patients for opioid use and opioid use disorder at the first prenatal visit. Obtain a thorough history of substance use and review the Prescription Drug Monitoring Program to determine if patients have received prior prescriptions for opioids or other high-risk drugs such as benzodiazepines. Discuss the risks and benefits of opioid use during pregnancy, including the risk of becoming physiologically dependent on opioids, the possibility for NOWS, and how long-term opioid use may affect care during a future pregnancy. In women undergoing uncomplicated normal spontaneous vaginal birth, consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, use in combination with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate. Use immediate-release opioids instead of extended-release or long-acting opioids; order the lowest effective dosage and prescribe no greater quantity of opioids than needed for the expected duration of such pain severe enough to require opioids. For women using opioids for chronic pain, consider strategies to avoid or minimize the use of opioids, including alternative pain therapies (i.e., nonpharmacologic) and nonopioid pharmacologic treatments. Opioid agonist pharmacotherapy (e.g., methadone or buprenorphine) is preferable to medically supervised withdrawal in pregnant women with opioid use disorder. In animal reproductive studies, oliceridine reduced live litter size at birth and increased postnatal pup mortality between birth and postnatal day 4 when administered intravenously to rats from organogenesis through weaning at doses producing clinically relevant plasma exposure. Oliceridine did not affect embryofetal development in rats and rabbits when administered intravenously during organogenesis at doses producing plasma exposures 7 and 8 times the estimated plasma exposure at the maximum recommended human dose (MRHD) on an AUC basis, respectively.
It is not known whether oliceridine is present in human milk. The effects of oliceridine on a breast-feeding infant and milk production have not been evaluated. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for oliceridine and any potential adverse effects on the breast-fed infant from oliceridine or the underlying medical condition. Monitor infants exposed to oliceridine through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration is discontinued or breast-feeding is stopped.
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.
General dosing information:
-Individualize dosing for each patient; consider severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse. Use the lowest effective dose for the shortest duration consistent with individual treatment goals.
-Monitor patients closely for respiratory depression, especially within the first 24 to 48 hours after initiation and dose escalation, and adjust the dosage accordingly. Continually reevaluate patients to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as to monitor for the development of addiction, abuse, or misuse. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the opioid dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
-If patients reach a 27 mg cumulative daily oliceridine dose and analgesia is still required, use an alternative analgesic regimen until oliceridine can be resumed the next day.
-It is estimated that oliceridine 1 mg IV is approximately equipotent to morphine 5 mg IV. As individual patients differ in their response to opioids, use this comparison only as a guide. Refer to the Opioid Agonists Drug Class Overview for approximate equianalgesic doses.
-When a patient who has been taking opioids regularly and may be physically dependent no longer requires therapy with oliceridine, taper the dose gradually while monitoring carefully for signs and symptoms of withdrawal.
For the treatment of acute, severe pain where treatment with an intravenous opioid is appropriate and for which alternative treatments are inadequate:
Intravenous dosage:
Adults: 1.5 mg IV, then 0.75 mg IV every 1 hour as needed. Max: 3 mg/dose and 27 mg/day. Use beyond 48 hours has not been evaluated.
Intravenous dosage (Patient-Controlled Analgesia [PCA]):
Adults: 1.5 mg IV, then 0.35 mg IV on-demand with a 6-minute lock-out interval. May consider 0.5 mg on-demand for some patients if the potential benefits outweigh the risks. Max: 27 mg/day. Use beyond 48 hours has not been evaluated.
Maximum Dosage Limits:
-Adults
3 mg/dose IV and 27 mg/day IV.
-Geriatric
3 mg/dose IV and 27 mg/day IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Patients with mild or moderate hepatic disease may require less frequent oliceridine dosing. When using oliceridine in patients with severe hepatic disease, consider reducing the initial dose, and administer subsequent doses only after a careful review of the patient's severity of pain and overall clinical status.
Patients with Renal Impairment Dosing
Dosage adjustment is not required.
*non-FDA-approved indication
Abiraterone: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and abiraterone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and abiraterone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If abiraterone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
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; Dihydrocodeine: (Major) Concomitant use of oliceridine with dihydrocodeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with dihydrocodeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of opioid agonists with pyrilamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with pyrilamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
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; Codeine: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Acetaminophen; Dextromethorphan: (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
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) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
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 oliceridine with hydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydrocodone 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Acetaminophen; Oxycodone: (Major) Concomitant use of oliceridine with oxycodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with oxycodone 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. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets. 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.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and adagrasib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and adagrasib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with adagrasib as it can inhibit multiple CYP enzymes. If adagrasib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A and CYP2D6 substrate and adagrasib is a strong CYP3A inhibitor and moderate CYP2D6 inhibitor.
Alfentanil: (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.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Almotriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
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 oliceridine with alprazolam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with alprazolam 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.
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.
Amiloride: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Amitriptyline: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Amobarbital: (Major) Concomitant use of oliceridine with amobarbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with amobarbital 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.
Amoxapine: (Major) Concomitant use of oliceridine with amoxapine may cause excessive sedation and somnolence. Limit the use of oliceridine with amoxapine 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.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and clarithromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and clarithromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If clarithromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Amphetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Amphetamine; Dextroamphetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Amphetamines: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Apalutamide: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with apalutamide is necessary; consider increasing the dose of oliceridine as needed. If apalutamide is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Apomorphine: (Major) Concomitant use of oliceridine with apomorphine may cause excessive sedation and somnolence. Limit the use of oliceridine with apomorphine 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.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and a multi-day regimen of aprepitant, fosaprepitant is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and aprepitant, fosaprepitant may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If aprepitant, fosaprepitant is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and when administered as a 3-day oral regimen, aprepitant is a moderate CYP3A4 inhibitor; single oral and IV doses have not been shown to alter concentrations of CYP3A4 substrates.
Aripiprazole: (Moderate) Concomitant use of oliceridine with aripiprazole may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Artemether; Lumefantrine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and lumefantrine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and lumefantrine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If lumefantrine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and lumefantrine is a moderate CYP2D6 inhibitor.
Asenapine: (Moderate) Concomitant use of oliceridine with asenapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of oliceridine with butalbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with butalbital 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.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of oliceridine with orphenadrine may cause excessive sedation and somnolence. Limit the use of oliceridine with orphenadrine 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.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of oliceridine with carisoprodol may cause excessive sedation and somnolence. Limit the use of oliceridine with carisoprodol 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. (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oliceridine with oxycodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with oxycodone 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. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets. 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.
Atazanavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and atazanavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and atazanavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If atazanavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and atazanavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and atazanavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If atazanavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Atenolol; Chlorthalidone: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Atropine: (Moderate) Concomitant use of oliceridine with atropine may cause excessive sedation and somnolence. Limit the use of oliceridine with atropine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with atropine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Atropine; Difenoxin: (Moderate) Concomitant use of oliceridine with atropine may cause excessive sedation and somnolence. Limit the use of oliceridine with atropine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with atropine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (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.
Azelastine: (Major) Concomitant use of oliceridine with azelastine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Azelastine; Fluticasone: (Major) Concomitant use of oliceridine with azelastine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Azilsartan; Chlorthalidone: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Baclofen: (Major) Concomitant use of oliceridine with baclofen may cause excessive sedation and somnolence. Limit the use of oliceridine with baclofen 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.
Belladonna; Opium: (Major) Concomitant use of oliceridine with opium may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with opium 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) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with belladonna. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of oliceridine with benzhydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with benzhydrocodone 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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) If concomitant use of oliceridine and methylene blue 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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with hyoscyamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Benzphetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Benztropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with benztropine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Berotralstat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and berotralstat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and berotralstat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If berotralstat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and berotralstat is a moderate CYP3A4 and CYP2D6 inhibitor.
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.
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; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
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 oliceridine with brexpiprazole may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Brimonidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Brimonidine; Brinzolamide: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Brimonidine; Timolol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Brompheniramine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Brompheniramine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Bumetanide: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Buprenorphine: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Buprenorphine; Naloxone: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Bupropion: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. 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.
Bupropion; Naltrexone: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. 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.
Buspirone: (Moderate) If concomitant use of oliceridine 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 oliceridine with butalbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with butalbital 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.
Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of oliceridine with butalbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with butalbital 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.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of oliceridine with butalbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with butalbital 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. (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of oliceridine with butalbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with butalbital 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. (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Butorphanol: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
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 patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Cannabidiol: (Moderate) Concomitant use of oliceridine with cannabidiol may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Capivasertib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and capivasertib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and capivasertib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If capivasertib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and capivasertib is a moderate CYP2D6 inhibitor.
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 patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Carbamazepine: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oliceridine as needed. If carbamazepine is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbidopa; Levodopa: (Major) Concomitant use of oliceridine with levodopa may cause excessive sedation and somnolence. Limit the use of oliceridine with levodopa 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.
Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of oliceridine with entacapone may cause excessive sedation and somnolence. Limit the use of oliceridine with entacapone 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. (Major) Concomitant use of oliceridine with levodopa may cause excessive sedation and somnolence. Limit the use of oliceridine with levodopa 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.
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 oliceridine 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 oliceridine with carisoprodol may cause excessive sedation and somnolence. Limit the use of oliceridine with carisoprodol 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.
Celecoxib; Tramadol: (Major) Concomitant use of oliceridine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with tramadol 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.
Cenobamate: (Moderate) Concomitant use of oliceridine with cenobamate may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Ceritinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ceritinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ceritinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ceritinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Cetirizine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cetirizine; Pseudoephedrine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chloramphenicol: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and chloramphenicol is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and chloramphenicol may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If chloramphenicol is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
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 oliceridine with chlordiazepoxide may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with chlordiazepoxide 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; Amitriptyline: (Major) Concomitant use of oliceridine with chlordiazepoxide may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with chlordiazepoxide 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. (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with chlordiazepoxide may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with chlordiazepoxide 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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with clidinium. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlorothiazide: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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 opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of oliceridine with hydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydrocodone 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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 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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and chlorpromazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and chlorpromazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If chlorpromazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and chlorpromazine is a moderate CYP2D6 inhibitor.
Chlorthalidone: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Chlorzoxazone: (Major) Concomitant use of oliceridine with chlorzoxazone may cause excessive sedation and somnolence. Limit the use of oliceridine with chlorzoxazone 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.
Cinacalcet: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cinacalcet is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cinacalcet may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cinacalcet is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Ciprofloxacin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ciprofloxacin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ciprofloxacin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ciprofloxacin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor.
Citalopram: (Moderate) If concomitant use of oliceridine 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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and clarithromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and clarithromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If clarithromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
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.
Clobazam: (Major) Concomitant use of oliceridine with clobazam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with clobazam 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.
Clomipramine: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with clonazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with clonazepam 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.
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.
Clorazepate: (Major) Concomitant use of oliceridine with clorazepate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with clorazepate 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.
Clozapine: (Major) Concomitant use of oliceridine with clozapine may cause excessive sedation and somnolence. Limit the use of oliceridine with clozapine 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.
Cobicistat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Cocaine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cocaine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cocaine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cocaine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and cocaine is a strong CYP2D6 inhibitor.
Codeine: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Codeine; Guaifenesin: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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. (Major) Concomitant use of oliceridine with promethazine may cause excessive sedation and somnolence. Limit the use of oliceridine with promethazine 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.
Codeine; Promethazine: (Major) Concomitant use of oliceridine with codeine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with codeine 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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. (Major) Concomitant use of oliceridine with promethazine may cause excessive sedation and somnolence. Limit the use of oliceridine with promethazine 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.
Conivaptan: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and conivaptan is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and conivaptan may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If conivaptan is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and crizotinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and crizotinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If crizotinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor.
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 oliceridine with cyclobenzaprine may cause excessive sedation and somnolence. Limit the use of oliceridine with cyclobenzaprine 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Cyclosporine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cyclosporine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cyclosporine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cyclosporine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor.
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.
Dacomitinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and dacomitinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and dacomitinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If dacomitinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor.
Danazol: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and danazol is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and danazol may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If danazol is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Dantrolene: (Major) Concomitant use of oliceridine 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, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Daridorexant: (Moderate) Concomitant use of oliceridine with daridorexant may cause excessive sedation and somnolence. Limit the use of oliceridine with daridorexant 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.
Darifenacin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and darifenacin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and darifenacin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If darifenacin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and darifenacin is a moderate CYP2D6 inhibitor.
Darunavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and darunavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and darunavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If darunavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and darunavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and darunavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If darunavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and darunavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and darunavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If darunavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Delavirdine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and delavirdine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and delavirdine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with delavirdine as it can inhibit multiple CYP enzymes. If delavirdine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and delavirdine is a strong CYP3A4 inhibitor and moderate CYP2D6 inhibitor.
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 oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine 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: (Moderate) Concomitant use of oliceridine with deutetrabenazine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexchlorpheniramine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
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) If concomitant use of oliceridine and methylphenidate derivatives 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.
Dextroamphetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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: (Moderate) If concomitant use of oliceridine and dextromethorphan 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; Bupropion: (Moderate) If concomitant use of oliceridine and dextromethorphan 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. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. 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.
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) If concomitant use of oliceridine and dextromethorphan 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; Guaifenesin: (Moderate) If concomitant use of oliceridine and dextromethorphan 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; Guaifenesin; Phenylephrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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; Quinidine: (Moderate) If concomitant use of oliceridine and dextromethorphan 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. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and quinidine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinidine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinidine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor.
Diazepam: (Major) Concomitant use of oliceridine with diazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with diazepam 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 injectable diazepam is used with oliceridine, reduce the oliceridine dosage by at least one-third.
Dicyclomine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with dicyclomine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and diltiazem is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and diltiazem may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If diltiazem is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor.
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) Concomitant use of oliceridine with atropine may cause excessive sedation and somnolence. Limit the use of oliceridine with atropine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with atropine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (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.
Diuretics: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Dolasetron: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists 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.
Doxepin: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and dronedarone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and dronedarone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with dronedarone as it can inhibit multiple CYP enzymes. If dronedarone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and dronedarone is a moderate CYP3A4 and CYP2D6 inhibitor.
Droperidol: (Major) Concomitant use of oliceridine with droperidol may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Duloxetine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and duloxetine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and duloxetine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If duloxetine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and duloxetine is a moderate CYP2D6 inhibitor. 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.
Duvelisib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and duvelisib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and duvelisib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If duvelisib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Eletriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Eliglustat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and eliglustat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and eliglustat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If eliglustat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and eliglustat is a moderate CYP2D6 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cobicistat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cobicistat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cobicistat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Encorafenib: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with encorafenib is necessary; consider increasing the dose of oliceridine as needed. If encorafenib is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A substrate and encorafenib is a CYP3A inducer. Concomitant use with CYP3A inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Entacapone: (Major) Concomitant use of oliceridine with entacapone may cause excessive sedation and somnolence. Limit the use of oliceridine with entacapone 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.
Enzalutamide: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with enzalutamide is necessary; consider increasing the dose of oliceridine as needed. If enzalutamide is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Erythromycin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and erythromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and erythromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If erythromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Escitalopram: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and escitalopram is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and escitalopram may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If escitalopram is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor. 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.
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.
Estazolam: (Major) Concomitant use of oliceridine with estazolam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with estazolam 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.
Eszopiclone: (Major) Concomitant use of oliceridine 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 oliceridine 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.
Ethacrynic Acid: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking opioids. Alcohol consumption may result in additive CNS depression and may increase the risk for opioid overdose. Consider the patient's use of alcohol when prescribing opioid medications. If the patient is unlikely to be compliant with avoiding alcohol, consider prescribing naloxone especially if additional risk factors for opioid overdose are present.
Etomidate: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Fedratinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fedratinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fedratinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with fedratinib as it can inhibit multiple CYP enzymes. If fedratinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and fedratinib is a moderate CYP3A4 and CYP2D6 inhibitor.
Fenfluramine: (Moderate) Concomitant use of oliceridine with fenfluramine may cause excessive sedation and somnolence. Limit the use of oliceridine 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fentanyl: (Major) Concomitant use of oliceridine with fentanyl may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with fentanyl 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.
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.
Flavoxate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with flavoxate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fluconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fluconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If fluconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor.
Fluoxetine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fluoxetine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fluoxetine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with fluoxetine as it can inhibit multiple CYP enzymes. If fluoxetine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and fluoxetine and its metabolite, norfluoxetine, are a strong CYP2D6 inhibitor and moderate CYP3A4 inhibitor, respectively. 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.
Fluphenazine: (Moderate) Concomitant use of oliceridine with fluphenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with fluphenazine 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.
Flurazepam: (Major) Concomitant use of oliceridine with flurazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with flurazepam 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.
Fluvoxamine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fluvoxamine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fluvoxamine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If fluvoxamine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor. 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.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fosamprenavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fosamprenavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If fosamprenavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Fosphenytoin: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with fosphenytoin is necessary; consider increasing the dose of oliceridine as needed. If fosphenytoin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Frovatriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Furosemide: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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 opioid pain medications 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.
General anesthetics: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Givosiran: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and givosiran is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and givosiran may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If givosiran is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and givosiran is a moderate CYP2D6 inhibitor.
Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Granisetron: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists 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.
Grapefruit juice: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if use oliceridine and grapefruit juice; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and grapefruit juice may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with grapefruit juice as it can inhibit multiple CYP enzymes. If grapefruit juice is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and grapefruit juice is a strong CYP3A4 inhibitor and moderate CYP2D6 inhibitor.
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.
Guselkumab: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and guselkumab is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and guselkumab may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If guselkumab is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and guselkumab is a moderate CYP2D6 inhibitor.
Haloperidol: (Major) Concomitant use of oliceridine with haloperidol may cause excessive sedation and somnolence. Limit the use of oliceridine with haloperidol 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.
Homatropine; Hydrocodone: (Major) Concomitant use of oliceridine with hydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydrocodone 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with homatropine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Hydrocodone: (Major) Concomitant use of oliceridine with hydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydrocodone 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Hydrocodone; Ibuprofen: (Major) Concomitant use of oliceridine with hydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydrocodone 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. Avoid prescribing opioid cough medications in patients taking other opioid agonists. 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.
Hydromorphone: (Major) Concomitant use of oliceridine with hydromorphone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with hydromorphone 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.
Hydroxyzine: (Major) Concomitant use of oliceridine with hydroxyzine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Hyoscyamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with hyoscyamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) If concomitant use of oliceridine and methylene blue 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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with hyoscyamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Ibuprofen; Oxycodone: (Major) Concomitant use of oliceridine with oxycodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with oxycodone 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. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets. 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.
Idelalisib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and idelalisib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and idelalisib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If idelalisib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Iloperidone: (Moderate) Concomitant use of oliceridine with iloperidone may cause excessive sedation and somnolence. Limit the use of oliceridine with iloperidone 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.
Imatinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and imatinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and imatinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If imatinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Imipramine: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Indapamide: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Indinavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and indinavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and indinavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If indinavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Isavuconazonium: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and isavuconazonium is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and isavuconazonium may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If isavuconazonium is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Isocarboxazid: (Moderate) Concomitant use of oliceridine with monoamine oxidase inhibitors (MAOIs) may cause excessive sedation and somnolence. Limit the use of oliceridine with MAOIs 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Isoflurane: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oliceridine as needed. If rifampin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Isoniazid, INH; Rifampin: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oliceridine as needed. If rifampin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Itraconazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and itraconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and itraconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If itraconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Coadministration with itraconazole increased the oliceridine exposure by approximately 80% in healthy CYP2D6 poor metabolizers.
Ketamine: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Ketoconazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ketoconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ketoconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ketoconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and clarithromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and clarithromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If clarithromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Lasmiditan: (Moderate) Concomitant use of oliceridine with lasmiditan may cause excessive sedation and somnolence. Limit the use of oliceridine 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. 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.
Lefamulin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and oral lefamulin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and oral lefamulin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If oral lefamulin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with IV lefamulin.
Lemborexant: (Moderate) Concomitant use of oliceridine with lemborexant may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Lenacapavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and lenacapavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and lenacapavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If lenacapavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and letermovir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and letermovir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If letermovir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and letermovir is a moderate CYP3A4 inhibitor.
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) Concomitant use of oliceridine with levodopa may cause excessive sedation and somnolence. Limit the use of oliceridine with levodopa 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.
Levoketoconazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ketoconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ketoconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ketoconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Levomilnacipran: (Moderate) If concomitant use of oliceridine 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.
Levorphanol: (Major) Concomitant use of oliceridine with levorphanol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with levorphanol 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. Reduce the initial dose of levorphanol by approximately 50% or more. 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.
Linezolid: (Major) Avoid concomitant use of oliceridine with linezolid due to the risk of serotonin syndrome. If concomitant use is warranted, carefully monitor the patient, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lisdexamfetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Lithium: (Moderate) If concomitant use of oliceridine 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) Concomitant use of oliceridine with lofexidine may cause excessive sedation and somnolence. Limit the use of oliceridine with lofexidine 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.
Lonafarnib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and lonafarnib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and lonafarnib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If lonafarnib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ritonavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ritonavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ritonavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Lorazepam: (Major) Concomitant use of oliceridine with lorazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with lorazepam 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.
Lorcaserin: (Moderate) If concomitant use of oliceridine 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.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Loxapine: (Moderate) Concomitant use of opioid agonists, such as oliceridine, 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.
Lumateperone: (Moderate) Concomitant use of opioid agonists like oliceridine 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 oliceridine with lurasidone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with lurasidone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Maprotiline: (Major) Concomitant use of oliceridine with maprotiline may cause excessive sedation and somnolence. Limit the use of oliceridine with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Meclizine: (Moderate) Concomitant use of oliceridine with meclizine may cause excessive sedation and somnolence. Limit the use of oliceridine with meclizine 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.
Melatonin: (Moderate) Concomitant use of oliceridine with melatonin may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Meperidine: (Major) Concomitant use of oliceridine with meperidine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with meperidine 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.
Meprobamate: (Moderate) Concomitant use of oliceridine with meprobamate may cause excessive sedation and somnolence. Limit the use of oliceridine with meprobamate 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.
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 oliceridine with methadone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with methadone 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.
Methamphetamine: (Moderate) If concomitant use of oliceridine and amphetamines 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.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) If concomitant use of oliceridine and methylene blue 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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with hyoscyamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Methocarbamol: (Major) Concomitant use of oliceridine with methocarbamol may cause excessive sedation and somnolence. Limit the use of oliceridine with methocarbamol 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.
Methohexital: (Major) Concomitant use of oliceridine with methohexital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with methohexital 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.
Methscopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with methscopolamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
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: (Moderate) If concomitant use of oliceridine and methylene blue 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.
Methylphenidate Derivatives: (Moderate) If concomitant use of oliceridine and methylphenidate derivatives 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.
Methylphenidate: (Moderate) If concomitant use of oliceridine and methylphenidate derivatives 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.
Metoclopramide: (Moderate) Concomitant use of oliceridine with metoclopramide may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Metolazone: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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 oliceridine with midazolam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with midazolam 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.
Mifepristone: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and mifepristone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mifepristone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mifepristone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Milnacipran: (Moderate) If concomitant use of oliceridine 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.
Mirabegron: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and mirabegron is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mirabegron may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mirabegron is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor.
Mirtazapine: (Major) Concomitant use of oliceridine with mirtazapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Mitotane: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with mitotane is necessary; consider increasing the dose of oliceridine as needed. If mitotane is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Molindone: (Moderate) Concomitant use of opioid agonists like oliceridine 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: (Moderate) Concomitant use of oliceridine with monoamine oxidase inhibitors (MAOIs) may cause excessive sedation and somnolence. Limit the use of oliceridine with MAOIs 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Morphine: (Major) Concomitant use of oliceridine with morphine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with morphine 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. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. 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.
Morphine; Naltrexone: (Major) Concomitant use of oliceridine with morphine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with morphine 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. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. 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.
Nabilone: (Major) Avoid coadministration of opioid agonists with nabilone due to the risk of additive CNS depression.
Nalbuphine: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Naratriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Nefazodone: (Major) Concomitant use of oliceridine with nefazodone may cause excessive sedation and somnolence. Limit the use of oliceridine with nefazodone 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. Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and nefazodone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and nefazodone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If nefazodone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. 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.
Nelfinavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and nelfinavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and nelfinavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If nelfinavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor.
Neostigmine; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and netupitant is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and netupitant may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If netupitant is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor.
Nilotinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and nilotinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and nilotinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If nilotinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor.
Niraparib; Abiraterone: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and abiraterone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and abiraterone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If abiraterone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ritonavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ritonavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ritonavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Nirogacestat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and nirogacestat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and nirogacestat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If nirogacestat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
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 oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Olanzapine: (Major) Concomitant use of oliceridine with olanzapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with olanzapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and fluoxetine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fluoxetine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects; these effects may be more pronounced with fluoxetine as it can inhibit multiple CYP enzymes. If fluoxetine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 and CYP2D6 substrate and fluoxetine and its metabolite, norfluoxetine, are a strong CYP2D6 inhibitor and moderate CYP3A4 inhibitor, respectively. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olanzapine; Samidorphan: (Contraindicated) Salmidorphan is contraindicated in patients who are using opiate agonists or undergoing acute opioid withdrawal. Salmidorphan increases the risk of precipitating acute opioid withdrawal in patients dependent on opioids. Before initiating salmidorphan, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations, if a salmidorphan-treated patient requires opiates for anesthesia or analgesia, discontinue salmidorphan. The opiate agonist should be administered by properly trained individual(s), and the patient properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations, if a salmidorphan-treated patient requires opiate agonist treatment (e.g., for analgesia) discontinue salmidorphan at least 5 days before opioid treatment. Salmidorphan, as an opioid antagonist, may cause opioid treatment to be less effective or ineffective shortly after salmidorphan discontinuation. (Major) Concomitant use of oliceridine with olanzapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Ondansetron: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists 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.
Opiate Agonists-Antagonists: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Orphenadrine: (Major) Concomitant use of oliceridine with orphenadrine may cause excessive sedation and somnolence. Limit the use of oliceridine with orphenadrine 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.
Oxazepam: (Major) Concomitant use of oliceridine with oxazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with oxazepam 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.
Oxybutynin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with oxybutynin. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Oxycodone: (Major) Concomitant use of oliceridine with oxycodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with oxycodone 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. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets. 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.
Oxymorphone: (Major) Concomitant use of oliceridine with oxymorphone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with oxymorphone 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. Reduce the initial oxymorphone dosage by one-third to one-half. 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.
Paliperidone: (Moderate) Concomitant use of oliceridine with paliperidone may cause excessive sedation and somnolence. Limit the use of oliceridine with paliperidone 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.
Palonosetron: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists 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.
Panobinostat: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and panobinostat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and panobinostat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If panobinostat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and panobinostat is a moderate CYP2D6 inhibitor.
Paroxetine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and paroxetine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and paroxetine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If paroxetine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. 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.
Pegvisomant: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Pentazocine; Naloxone: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Pentobarbital: (Major) Concomitant use of oliceridine with pentobarbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with pentobarbital 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.
Perampanel: (Moderate) Concomitant use of oliceridine with perampanel may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Perphenazine: (Moderate) Concomitant use of oliceridine with perphenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with perphenazine 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. Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and perphenazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and perphenazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If perphenazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and perphenazine is a moderate CYP2D6 inhibitor.
Perphenazine; Amitriptyline: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with perphenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with perphenazine 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. Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and perphenazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and perphenazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If perphenazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and perphenazine is a moderate CYP2D6 inhibitor.
Phenelzine: (Moderate) Concomitant use of oliceridine with monoamine oxidase inhibitors (MAOIs) may cause excessive sedation and somnolence. Limit the use of oliceridine with MAOIs 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Phenobarbital: (Major) Concomitant use of oliceridine with phenobarbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with phenobarbital 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 for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with phenobarbital is necessary; consider increasing the dose of oliceridine as needed. If phenobarbital is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of oliceridine with phenobarbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with phenobarbital 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 for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with phenobarbital is necessary; consider increasing the dose of oliceridine as needed. If phenobarbital is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Moderate) Concomitant use of oliceridine with atropine may cause excessive sedation and somnolence. Limit the use of oliceridine with atropine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with atropine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Concomitant use of oliceridine with scopolamine may cause excessive sedation and somnolence. Limit the use of oliceridine with scopolamine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with scopolamine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with hyoscyamine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Phenytoin: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with phenytoin is necessary; consider increasing the dose of oliceridine as needed. If phenytoin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pimavanserin: (Moderate) Concomitant use of oliceridine with pimavanserin may cause excessive sedation and somnolence. Limit the use of oliceridine with pimavanserin 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.
Pimozide: (Major) Concomitant use of oliceridine with pimozide may cause excessive sedation and somnolence. Limit the use of oliceridine with pimozide 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.
Posaconazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and posaconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and posaconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If posaconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Pramipexole: (Major) Concomitant use of oliceridine with pramipexole may cause excessive sedation and somnolence. Limit the use of oliceridine 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. 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.
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 oliceridine with pregabalin may cause excessive sedation and somnolence. Limit the use of oliceridine with pregabalin 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.
Primidone: (Major) Concomitant use of oliceridine with primidone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with primidone 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 for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with primidone is necessary; consider increasing the dose of oliceridine as needed. If primidone is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Prochlorperazine: (Major) Concomitant use of oliceridine with prochlorperazine may cause excessive sedation and somnolence. Limit the use of oliceridine with prochlorperazine 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.
Promethazine: (Major) Concomitant use of oliceridine with promethazine may cause excessive sedation and somnolence. Limit the use of oliceridine with promethazine 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.
Promethazine; Dextromethorphan: (Major) Concomitant use of oliceridine with promethazine may cause excessive sedation and somnolence. Limit the use of oliceridine with promethazine 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. (Moderate) If concomitant use of oliceridine and dextromethorphan 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.
Promethazine; Phenylephrine: (Major) Concomitant use of oliceridine with promethazine may cause excessive sedation and somnolence. Limit the use of oliceridine with promethazine 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.
Propafenone: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and propafenone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and propafenone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If propafenone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and propafenone is a moderate CYP2D6 inhibitor.
Propantheline: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with propantheline. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Propofol: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Protriptyline: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with quazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with quazepam 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.
Quetiapine: (Major) Concomitant use of oliceridine with quetiapine may cause excessive sedation and somnolence. Limit the use of oliceridine 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 patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Quinidine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and quinidine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinidine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinidine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor.
Quinine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and quinine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and quinine is a moderate CYP2D6 inhibitor.
Ramelteon: (Moderate) Concomitant use of oliceridine with ramelteon may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Ranolazine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ranolazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ranolazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ranolazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and ranolazine is a moderate CYP2D6 inhibitor.
Rasagiline: (Major) Concomitant use of oliceridine with rasagiline may cause excessive sedation and somnolence. Limit the use of oliceridine with rasagiline 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. 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. 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.
Remifentanil: (Major) Concomitant use of oliceridine with remifentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with remifentanil 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.
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.
Ribociclib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ribociclib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ribociclib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ribociclib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ribociclib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ribociclib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ribociclib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifampin: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oliceridine as needed. If rifampin is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Rifapentine: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oliceridine as needed. If rifapentine is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Risperidone: (Major) Concomitant use of oliceridine with risperidone may cause excessive sedation and somnolence. Limit the use of oliceridine with risperidone 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.
Ritlecitinib: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ritlecitinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ritlecitinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ritlecitinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ritonavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ritonavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ritonavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Rizatriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Rolapitant: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and rolapitant is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and rolapitant may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If rolapitant is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor.
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.
Rotigotine: (Major) Concomitant use of oliceridine with rotigotine may cause excessive sedation and somnolence. Limit the use of oliceridine 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. 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.
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.
Scopolamine: (Moderate) Concomitant use of oliceridine with scopolamine may cause excessive sedation and somnolence. Limit the use of oliceridine with scopolamine 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 signs of urinary retention or reduced gastric motility when oliceridine is used concomitantly with scopolamine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Secobarbital: (Major) Concomitant use of oliceridine with secobarbital may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with secobarbital 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.
Selegiline: (Moderate) Concomitant use of oliceridine with selegiline may cause excessive sedation and somnolence. Limit the use of oliceridine with selegiline 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) If concomitant use of oliceridine and methylphenidate derivatives 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.
Serotonin-Receptor Agonists: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Serotonin-Receptor Antagonists: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists 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.
Sertraline: (Moderate) If concomitant use of oliceridine 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: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
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.
Spironolactone: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with St. John's Wort is necessary; consider increasing the dose of oliceridine as needed. If St. John's Wort is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. 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.
Stiripentol: (Moderate) Concomitant use of oliceridine with stiripentol may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Sufentanil: (Major) Concomitant use of oliceridine with sufentanil may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with sufentanil to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Sumatriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Sumatriptan; Naproxen: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Suvorexant: (Moderate) Concomitant use of oliceridine with suvorexant may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Tapentadol: (Major) Concomitant use of tapentadol with oliceridine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of tapentadol with oliceridine 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 oliceridine with tasimelteon may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Temazepam: (Major) Concomitant use of oliceridine with temazepam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with temazepam 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.
Terbinafine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and terbinafine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and terbinafine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If terbinafine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor.
Tetrabenazine: (Moderate) Concomitant use of oliceridine with tetrabenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with tetrabenazine 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.
Thalidomide: (Major) Avoid coadministration of opioid agonists with thalidomide due to the risk of additive CNS depression.
Thioridazine: (Major) Concomitant use of oliceridine with thioridazine may cause excessive sedation and somnolence. Limit the use of oliceridine with thioridazine 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. Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and thioridazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and thioridazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If thioridazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and thioridazine is a moderate CYP2D6 inhibitor.
Thiothixene: (Moderate) Concomitant use of opioid agonists like oliceridine 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.
Tizanidine: (Major) Concomitant use of oliceridine with tizanidine may cause excessive sedation and somnolence. Limit the use of oliceridine with tizanidine 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.
Tolcapone: (Major) Concomitant use of oliceridine with tolcapone may cause excessive sedation and somnolence. Limit the use of oliceridine with tolcapone 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.
Torsemide: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Tramadol: (Major) Concomitant use of oliceridine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with tramadol 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.
Tramadol; Acetaminophen: (Major) Concomitant use of oliceridine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with tramadol 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.
Trandolapril; Verapamil: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and verapamil is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and verapamil may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If verapamil is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor.
Tranylcypromine: (Moderate) Concomitant use of oliceridine with monoamine oxidase inhibitors (MAOIs) may cause excessive sedation and somnolence. Limit the use of oliceridine with MAOIs 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Trazodone: (Major) Concomitant use of oliceridine with trazodone may cause excessive sedation and somnolence. Limit the use of oliceridine with trazodone 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.
Triamterene: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Triazolam: (Major) Concomitant use of oliceridine with triazolam may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with triazolam 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.
Tricyclic antidepressants: (Major) Concomitant use of oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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 oliceridine with trifluoperazine may cause excessive sedation and somnolence. Limit the use of oliceridine with trifluoperazine 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.
Trihexyphenidyl: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with trihexyphenidyl. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
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 oliceridine with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and tucatinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and tucatinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If tucatinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
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 oliceridine with valproic acid may cause excessive sedation and somnolence. Limit the use of oliceridine 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.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Venlafaxine: (Moderate) If concomitant use of oliceridine 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) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and verapamil is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and verapamil may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If verapamil is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor.
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) If concomitant use of oliceridine and vilazodone 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.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and clarithromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and clarithromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If clarithromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Voriconazole: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and voriconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and voriconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If voriconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Vortioxetine: (Moderate) If concomitant use of oliceridine and vortioxetine 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.
Voxelotor: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and voxelotor is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and voxelotor may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If voxelotor is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zaleplon: (Major) Concomitant use of oliceridine 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 oliceridine 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.
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) Concomitant use of oliceridine with ziprasidone may cause excessive sedation and somnolence. Limit the use of oliceridine with ziprasidone 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. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Zolmitriptan: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists 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.
Zolpidem: (Major) Concomitant use of oliceridine 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 oliceridine 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. 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.
Oliceridine is a full opioid agonist and is relatively selective for the mu-opioid receptor. It is a mu-opioid receptor ligand that preferentially engages the G protein pathway, which is thought to be the principal pathway leading to the analgesic effects of opioids. Oliceridine has minimal to no recruitment of beta-arrestin signaling compared to conventional opioids, which is believed to reduce its opioid-related adverse event profile.
Oliceridine is administered intravenously. Mean steady-state Vd ranges from 90 to 120 L, indicating extensive tissue distribution. Plasma protein binding is 77%. Oliceridine is primarily metabolized by CYP2D6 and CYP3A4, with minor contributions from CYP2C9 and CYP2C19 into inactive metabolites. Metabolic clearance occurs via oxidation with subsequent glucuronidation. Other biotransformation pathways include N-dealkylation, glucuronidation, and dehydrogenation. The majority of metabolites (70%) and a small amount of parent drug (0.97% to 6.75% of the dose) are excreted in the urine, with the remainder of metabolites eliminated in the feces. The half-life of oliceridine is 1.3 to 3 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP2C19, CYP2D6, CYP3A4
Oliceridine is primarily metabolized by CYP2D6 and CYP3A4, with minor contributions from CYP2C9 and CYP2C19. Only the inhibition of CYP2D6 and CYP3A4 significantly affects drug metabolism. Oliceridicine does not inhibit any P450 isoenzymes at clinically relevant concentrations. In vitro data indicate oliceridine is not an inhibitor of any of the major drug transporters (e.g., BCRP, MDR1).
-Route-Specific Pharmacokinetics
Intravenous Route
Onset of analgesia is expected within 2 to 5 minutes after the initial dose. Mean drug clearance decreases slightly with increasing dose, resulting in greater than proportional exposure, especially at doses more than 2 mg. Oliceridine pharmacokinetics were not substantially changed (except for peak concentrations) when administered over different infusion times.
-Special Populations
Hepatic Impairment
Vd and half-life are increased in patients with moderate or severe hepatic impairment. Estimated Vd in subjects with moderate or severe impairment was 212 and 348 L, respectively, compared to healthy subjects (126 L) or those with mild hepatic impairment (167 L). Half-life was increased to 4.3 and 5.8 hours in subjects with moderate and severe hepatic impairment, respectively, compared to those with no (2.1 hours) or mild (2.6 hours) impairment. Clearance and total exposure were similar between all groups.
Renal Impairment
There was no significant difference in oliceridine clearance in subjects with end-stage renal disease compared to healthy subjects.
Other
CYP2D6 Poor Metabolizers
In CYP2D6 poor metabolizers, plasma clearance is approximately 50% of the plasma clearance in subjects who are nonpoor metabolizers. AUC was approximately 2-fold higher in healthy CYP2D6 poor metabolizers than in subjects who are nonpoor metabolizers.