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Prescribing Information HIGHLIGHTS OF PRESCRIBING INFORMATION • Supplemental doses of 0.75 mg can be administered, beginning 1 hour after These highlights do not include all the information needed to use the initial dose, and hourly thereafter, as needed. (2.2) OLINVYK ™ safely and effectively. See full prescribing information for • Do not stop OLINVYK in a physically-dependent patient. (2.4) OLINVYK. _____________ ______________ DOSAGE FORMS AND STRENGTHS OLINVYK (oliceridine) injection, for intravenous use, CII Injection: Initial U.S. Approval: 2020 • 1 mg/mL and 2 mg/2 ml (1 mg/mL) in single-dose vials WARNING: ADDICTION, ABUSE AND MISUSE; LIFE- • 30 mg/30 mL (1 mg/mL) in single-patient-use vial, For PCA Use Only THREATENING RESPIRATORY DEPRESSION; NEONATAL (3) OPIOID WITHDRAWAL SYNDROME; and RISKS FROM ___________________ ____________________ CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CONTRAINDICATIONS CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS • Significant respiratory depression (4) See full prescribing information for complete boxed warning. • Acute or severe bronchial asthma in an unmonitored setting or in absence • OLINVYK exposes patients and other users to the risks of opioid of resuscitative equipment (4) addiction, abuse, and misuse, Which can lead to overdose and death. • Known or suspected gastrointestinal obstruction, including paralytic ileus Assess each patient’s risk before prescribing, and monitor regularly (4) for the development of behaviors or conditions. (5.1) • Known hypersensitivity to oliceridine (4) • Serious, life-threatening, or fatal respiratory depression may occur. ______________ _______________ Monitor for respiratory depression, especially during initiation or WARNINGS AND PRECAUTIONS folloWing a dose increase. (5.2) Potential for QT Prolongation with Daily Doses Exceeding 27 mg: May • Prolonged use of OLINVYK during pregnancy can result in increase risk for QT interval prolongation. Do not exceed a cumulative daily neonatal opioid WithdraWal syndrome, Which may be life- dose of 27 mg. (5.5) threatening if not recognized and treated. If prolonged opioid use is required in a pregnant Woman, advise the patient of the risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary neonatal opioid WithdraWal syndrome and ensure that appropriate Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, treatment Will be available. (5.3) particularly during initiation and titration. (5.7) • Concomitant use of OLINVYK with benzodiazepines or other CNS Adrenal Insufficiency: If diagnosed, treat with physiologic replacement depressants, including alcohol, may result in profound sedation, corticosteroids and wean the patient off the opioid. (5.8) respiratory depression, coma, and death. Reserve concomitant Severe Hypotension: Monitor patients during initiation or titration. Avoid prescribing for use in patients for Whom alternative treatment use of OLINVYK in patients with circulatory shock. (5.9) options are inadequate; limit dosages and durations to the minimum required; and folloW patients for signs and symptoms of Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, respiratory depression and sedation. (5.4) Head Injury, or Impaired Consciousness: Monitor for signs of sedation and respiratory depression. Avoid the use of OLINVYK in patients with impaired _________________ __________________ consciousness or coma. (5.10) INDICATIONS AND USAGE ___________________ ____________________ ADVERSE REACTIONS OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for The most common (incidence ≥10%) adverse reactions in controlled clinical whom alternative treatments are inadequate. (1) trials (Studies 1 and 2) were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. (6.1) Limitations of Use To report SUSPECTED ADVERSE REACTIONS, contact Trevena, Inc. Because of the risks of addiction, abuse, and misuse with opioids, even at at 1-844-465-4686 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch recommended doses, reserve OLINVYK for use in patients for whom ___________________ ____________________ alternative treatment options [e.g., non-opioid analgesics or opioid DRUG INTERACTIONS combination products]: Moderate and Strong CYP2D6 and CYP3A4 Inhibitors: Patients may require • Have not been tolerated, or are not expected to be tolerated less frequent dosing. Monitor closely and administer subsequent doses based on severity of pain and patient response. (5.6, 7) • Have not provided adequate analgesia, or are not expected to provide adequate analgesia. (1) Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue OLINVYK if serotonin syndrome is suspected. (7) The cumulative total daily dose should not exceed 27 mg. (2.2, 5.5). ______________ _______________ Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use DOSAGE AND ADMINISTRATION with OLINVYK because they may reduce analgesic effect of OLINVYK or • Use the lowest effective dosage for the shortest duration consistent with precipitate withdrawal symptoms. (7) individual patient treatment goals. (2.1) ______________ _______________ USE IN SPECIFIC POPULATIONS • Individualize dosing based on the severity of pain, patient response, prior Pregnancy: May cause fetal harm (8.1) analgesic experience, and risk factors for addiction, abuse, and misuse. (2.1) Decreased CYP2D6 function: Patients may require less frequent dosing. Monitor closely and administer subsequent doses based on severity of pain • Initiate treatment with a 1.5 mg dose. (2.2) and patient response. (8.8) • 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 See 17 for PATIENT COUNSELING INFORMATION considered. (2.2) Revised: 11/2020 1 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: ADDICTION, ABUSE AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS 7 DRUG INTERACTIONS 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy 2.1 Important Dosage and Administration Instructions 8.2 Lactation 2.2 Dosing Information 8.3 Females and Males of Reproductive Potential 2.3 Titration and Maintenance Therapy 8.4 Pediatric Use 2.4 Safe Reduction or Discontinuation of OLINVYK 8.5 Geriatric Use 3 DOSAGE FORMS AND STRENGTHS 8.6 Renal Impairment 4 CONTRAINDICATIONS 8.7 Hepatic Impairment 5 WARNINGS AND PRECAUTIONS 8.8 Poor Metabolizers of CYP2D6 Substrates 5.1 Addiction, Abuse, and Misuse 9 DRUG ABUSE AND DEPENDENCE 5.2 Life-Threatening Respiratory Depression 9.1 Controlled Substance 5.3 Neonatal Opioid Withdrawal Syndrome 9.2 Abuse 5.4 Risks from Concomitant Use with Benzodiazepines or Other 9.3 Dependence CNS Depressants 10 OVERDOSAGE 5.5 Potential for QT prolongation with Daily Doses exceeding 27 10.1 Clinical Presentation mg 10.2 Treatment of Overdose 5.6 Risk of Use in Patients with Decreased Cytochrome P450 2D6 11 DESCRIPTION Function or Concomitant Use or Discontinuation with 12 CLINICAL PHARMACOLOGY Cytochrome P450 3A4 Inhibitors and Inducers 12.1 Mechanism of Action 5.7 Life-Threatening Respiratory Depression in Patients with 12.2 Pharmacodynamics Chronic Pulmonary Disease or in Elderly, Cachectic, or 12.3 Pharmacokinetics Debilitated Patients 12.5 Pharmacogenomics 5.8 Adrenal Insufficiency 13 NONCLINICAL TOXICOLOGY 5.9 Severe Hypotension 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.10 Risks of Use in Patients with Increased Intracranial Pressure, 13.2 Animal Toxicology and/or Pharmacology Brain Tumors, Head Injury, or Impaired Consciousness 14 CLINICAL STUDIES 5.11 Risks of Use in Patients with gastrointestinal Conditions 14.1 Orthopedic Surgery - Bunionectomy 5.12 Increased Risk of Seizures in Patients with Seizure Disorders 14.2 Plastic Surgery - Abdominoplasty 5.13 Withdrawal 16 HOW SUPPLIED/STORAGE AND HANDLING 5.14 Risks of Driving and Operating Machinery 17 PATIENT COUNSELING INFORMATION 5.15 Patient-Controlled Analgesia (PCA) 6 ADVERSE REACTIONS *Sections or subsections omitted from the full prescribing information 6.1 Clinical Studies Experience are not listed. 2 FULL PRESCRIBING INFORMATION WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS Addiction, Abuse, and Misuse 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 before prescribing OLINVYK, and monitor all patients regularly for the development of behaviors or conditions [see Warnings and Precautions (5.1)]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK. Monitor for respiratory depression, especially during initiation of OLINVYK or following a dose increase [see Warnings and Precautions (5.2)]. Neonatal Opioid Withdrawal Syndrome Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant
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