Oliceridine

FDA Drug Information • Also known as: Olinvyk

Brand Names: Olinvyk
Route: INTRAVENOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK Addiction, Abuse, and Misuse Because the use of OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 )] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential [see Warnings and Precautions ( 5.2 )]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of OLINVYK and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )]. Neonatal Opioid Withdrawal Syndrome Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions ( 5.4 )]. WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK See full prescribing information for complete boxed warning. OLINVYK exposes users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and reassess regularly for the development of behaviors or conditions. ( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential. ( 5.2 ) Concomitant use of OLINVYK with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. ( 5.4 , 7 ) Advise pregnant women using opioids for an extended period of time of the risks of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. ( 5.3 )

Description

11 DESCRIPTION The active ingredient in OLINVYK is oliceridine, an opioid agonist. Oliceridine fumarate is a white to lightly-colored solid that is sparingly soluble in water. The chemical name for oliceridine fumarate is [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine fumarate, and the molecular formula is C 22 H 30 N 2 O 2 S·C 4 H 4 O 4 . The theoretical average molecular mass is 502.62 (fumarate salt) and 386.55 (free base). The structural formula of oliceridine fumarate is: OLINVYK (oliceridine) injection is a clear, colorless, sterile, preservative-free solution, pH 6.4 to 7.4, in a glass vial for intravenous use. Each milliliter of the solution contains 1.0 mg of oliceridine free base (1.3 mg of oliceridine fumarate salt), as well as L-histidine and mannitol, in water for injection. Structural Formula

What Is Oliceridine Used For?

1 INDICATIONS AND USAGE OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration [see Warnings and Precautions ( 5.1 )] , and persist over the course of therapy, reserve opioid analgesics, including OLINVYK, for use in patients for whom alternative treatment options are ineffective, not management of pain. The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation [see Warnings and Precautions ( 5.5 ] . OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. ( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including OLINVYK, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.( 1 , 5.1 ) The cumulative total daily dose should not exceed 27 mg. ( 2.1 , 2.2 , 5.5 ).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For intravenous administration only. OLINVYK should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Reserve titration to higher doses of OLINVYK for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse and misuse. ( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OLINVYK. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Initiate treatment with a 1.5 mg dose. ( 2.2 ) For patient controlled analgesia (PCA), recommended demand dose is 0.35 mg, with a 6-minute lock-out. A demand dose of 0.5 mg may be considered. ( 2.2 ) Supplemental doses of 0.75 mg can be administered, beginning 1 hour after the initial dose, and hourly thereafter, as needed. ( 2.2 ) Periodically reassess patients receiving OLINVYK to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.3 ) Do not rapidly reduce or abruptly discontinue OLINVYK in a physically-dependent patient. ( 2.4 , 5.14 ) 2.1 Important Dosage and Administration Instructions For intravenous administration only. OLINVYK should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Individual single doses greater than 3 mg have not been evaluated. The cumulative daily dose should not exceed 27 mg. OLINVYK 30 mg/30 mL (1mg/mL) vial is intended for patient-controlled analgesia (PCA) use only. Draw OLINVYK directly from the vial into the PCA syringe or IV bag without diluting. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5 )] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of OLINVYK for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Use of OLINVYK beyond 48 hours has not been studied in controlled clinical trials. There is variability in opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.9 )] Severe Hypotension [see Warnings and Precautions ( 5.10 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Withdrawal [see Warnings and Precautions ( 5.14 )] The most common (incidence ≥10%) adverse reactions in controlled clinical trials (Studies 1 and 2) were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Trevena, Inc. at 1-844-465-4686 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 1535 patients were treated with OLINVYK in controlled and open-label trials in patients with moderate to severe acute pain. Of these, 1181 patients received a total daily dose ≤27 mg and 354 patients received a total daily dose >27 mg during the first 24-hour treatment period. Among patients who received a daily dose of >27 mg, 198 patients received a daily dose between 27 mg and 40 mg, and 142 patients received a daily dose >40 mg. The most common adverse drug reactions (≥10%) in controlled efficacy trials (Study 1 and Study 2) were nausea, vomiting, dizziness, headache, constipation, pruritus and hypoxia. Adverse reactions leading to discontinuation of OLINVYK were hypotension, hypoxia, nausea, hypoventilation, oxygen saturation decreased, alanine aminotransferase increased, aspartate aminotransferase increased, electrocardiogram QT prolongation, and urticaria. In two randomized, double-blind, placebo- and morphine-controlled studies, when stratified by 27 mg daily dosing limit, discontinuation of OLINVYK due to adverse reactions occurred in 4% of patients who received a daily dose ≤ 27 mg, and less than 1% of patients who received a daily dose >27 mg. In these same studies, discontinuation due to adverse reactions occurred in 5% of morphine-treated patients, and no placebo-treated patients. In an open-label safety study, discontinuation of OLINVYK due to adverse drug reactions occurred in 3% of patients who received a daily dose ≤ 27 mg, and 1% of patients who received a daily dose >27 mg. In two randomized, double-blind, placebo- and morphine-controlled studies in patients with moderate to severe acute pain following either orthopedic surgery-bunionectomy (Study 1), or plastic surgery-abdominoplasty (Study 2), patients received one of three OLINVYK dosing regimens, a morphine- control regimen, or a volume‑matched placebo-control regimen. All dosing regimens were administered via patient-controlled analgesia (PCA), allowing patients to individually titrate the dose available to an acceptable level of analgesia. Patients were treated for up to 48 hours in the bunionectomy study (Study 1), and for up to 24 hours in the abdominoplasty study(Study 2) [see Clinical Studies ( 14 )]. The loading dose for all OLINVYK treatment regimens was 1.5 mg; demand doses were 0.1, 0.35, or 0.5 mg, according to assigned treatment group; supplemental doses of 0.75 mg were permitted, beginning 1 hour after the loading dose, and hourly thereafter, as needed. The loading dose for the morphine treatment regimen was 4 mg; the...

Drug Interactions

7 DRUG INTERACTIONS Table 6 includes clinically significant drug interactions with OLINVYK. Table 6: Clinically Significant Drug Interactions with OLINVYK Moderate to Strong Inhibitors of CYP2D6 Clinical Impact: Concomitant administration of a moderate to strong CYP2D6 inhibitor can increase the plasma concentration of oliceridine [see Clinical Pharmacology ( 12.3 )] , resulting in increased or prolonged opioid effects. Intervention: If concomitant use is necessary, patients taking a moderate to strong CYP2D6 inhibitor may require less frequent dosing of OLINVYK. Monitor 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 a CYP2D6 inhibitor is discontinued, increase of the OLINVYK dosage may be considered until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Paroxetine, fluoxetine, quinidine, bupropion Moderate to Strong Inhibitors of CYP3A4 Clinical Impact: The concomitant administration of moderate to strong CYP3A4 inhibitors can increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid adverse reactions. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oliceridine concentration may decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oliceridine [see Warnings and Precautions ( 5.14 )] . Intervention: Caution should be used when administering OLINVYK to patients taking inhibitors of the CYP3A4 enzyme. If concomitant use is necessary, patients taking a CYP3A4 inhibitor may require less frequent dosing. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, increase of the OLINVYK dosage may be considered until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir). Strong and Moderate CYP3A4 Inhibitors and CYP2D6 Inhibitors Clinical Impact: OLINVYK is primarily metabolized by both CYP3A4 and CYP2D6. Compared to inhibition of either metabolic pathway, inhibition of both pathways can result in a greater increase of the plasma concentrations of oliceridine and prolong opioid adverse reactions [See Clinical Pharmacology ( 12.3 )]. Intervention: Patients who are CYP2D6 normal metabolizers taking a CYP2D6 inhibitor, and a strong CYP3A4 inhibitor (or discontinuation of CYP3A4 inducers) may require less frequent dosing. Patients who are known CYP2D6 poor metabolizers and taking a CYP3A4 inhibitor (or discontinuation of CYP3A4 inducers) may require less frequent dosing. These patients should be closely monitored for respiratory depression and sedation at frequent intervals, and subsequent doses should be based on the patient’s severity of pain and response to...

Contraindications

4 CONTRAINDICATIONS OLINVYK is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.2 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.8 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.12 )] Known hypersensitivity to oliceridine (e.g., anaphylaxis) Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Known hypersensitivity to oliceridine ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may result in neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . There are no available data on OLINVYK use in pregnant women to evaluate for a drug-associated risk of major birth defects and miscarriage or adverse maternal outcomes. There are adverse outcomes reported within detal exposure to opioid analgesics (see Clinical Considerations) . 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 had no effect on embryo-fetal 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 (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use,...

Overdosage

10 OVERDOSAGE Clinical Presentation Acute overdose with OLINVYK can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. While naloxone reversal of OLINVYK’s effects has not been established in humans, some pharmacological effects (analgesia) of oliceridine have been shown to be reversed by naloxone in animals [see Clinical Pharmacology ( 12.2 )] . For clinically significant respiratory or circulatory depression secondary to oliceridine overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of oliceridine in OLINVYK injection, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING OLINVYK (oliceridine) injection is a clear, colorless, preservative free solution for intravenous use supplied as follows: NDC# 71308-011-10: 1 mg/mL, sterile solution in single-dose, 2 mL clear glass vials with gray stoppers topped with overseals with gray plastic flip-off caps (carton of 10 vials) NDC# 71308-021-10: 2 mg/2 mL (1 mg/mL), sterile solution in single-dose, 2 mL clear glass vials with gray stoppers topped with overseals with orange plastic flip-off caps (carton of 10 vials) NDC# 71308-301-10: 30 mg/30 mL (1 mg/mL), sterile solution in single-patient-use, 30 mL clear glass vials with gray stoppers topped with overseals with purple plastic flip-off caps (carton of 10 vials). For PCA Use Only. Store at controlled room temperature 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from freezing. Protect from light.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.