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Addiction, Abuse, And Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Neonatal Opioid Withdrawal Syndrome; And Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants; Risk Evaluation and Mitigation Strategy (REMS)

Addiction, Abuse, and Misuse

  • Buprenorphine 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 Buprenorphine, and monitor all patients regularly for the development of these behaviors and conditions. 
  • Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose. 

Life-Threatening Respiratory Depression

  • Serious, life-threatening, or fatal respiratory depression may occur with use of Buprenorphine. Monitor for respiratory depression, especially during initiation of Buprenorphine or following a dose increase. Misuse or abuse of Buprenorphine by chewing, swallowing, snorting or injecting buprenorphine extracted from the buccal film will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death 
  • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

Accidental Exposure

  • Accidental exposure to even one dose of Buprenorphine, especially in children, can result in a fatal overdose of buprenorphine 

Neonatal Opioid Withdrawal Syndrome

  • Prolonged use of Buprenorphine 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 woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

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 opioids and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

Risk of Serious Harn or Death with Intravenous Administration; SUBLOCADE Risk Evaluation & Mitigation Strategy

  • Serious harm or death could result if administered intravenously. SUBLOCADE is only available through a restricted program called the SUBLOCADE REMS Program. Healthcare settings and pharmacies that order and dispense SUBLOCADE must be certified in this program and comply with the REMS requirements.

Pediatric Use

  • The safety and efficacy of buprenorphine in patients under 18 years of age has not been established. Buprenorphine has been evaluated in an open-label clinical trial in pediatric patients. However, definitive conclusions are not possible because of the small sample size.

Opiod Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to

  • complete a REMS-compliant education program,
  • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
  • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
  • consider other tools to improve patient, household, and community safety.

FDA and Industry Communications

Index to FDA Drug Safety Information

Approved Risk Evaluation and Mitigation Strategies (REMS)

Opioid Analgesics

SUBLOCADE (Buprenorphine Extented-Release) Injection

Buprenorphine Transmucosal Products for Opiod Dependence (BTOD)

Patient Counseling Information

Medication Guides

Patient Medication Guide - BELBUCA
Patient Medication Guide - BUTRANS
Patient Medication Guide - SUBLOCADE

Patient Medication Guide - BUNAVAIL
Patient Medication Guide - SUBOXONE
Patient Medication Guide - ZUBSOLV

Patient Medication Guide - CASSIPA

Package Inserts



Updated April 2021