Buprenorphine

Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use 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 buprenorphine transdermal system, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic.

Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa- opioid receptors, an agonist at delta-opioid receptors, and a partial agonist at ORL-1 (nociceptin) receptors. The contributions of these actions to its analgesic profile are unclear.

Buprenorphine transdermal system should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Buprenorphine transdermal system doses of 7.5, 10, 15, and 20 mcg/hour are only for use in patients receiving, for one week or longer, daily opioid doses up to 80 mg/day of oral morphine or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of buprenorphine transdermal system 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.

Buprenorphine transdermal system is contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment Known or suspected gastrointestinal obstruction, including paralytic ileus Hypersensitivity (e.g., anaphylaxis) to buprenorphine Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected gastrointestinal obstruction, including paralytic ileus. Hypersensitivity to buprenorphine

Boxed warning (serious and life-threatening risks from use of buprenorphine transdermal system): Addiction, Abuse, and Misuse Because the use of buprenorphine transdermal system 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. Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation.

The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Interactions with Benzodiazepines or Other CNS Depressants Neonatal Opioid Withdrawal Syndrome Application Site Skin Reactions Opioid-Induced Hyperalgesia and Allodynia Adrenal Insufficiency Severe Hypotension Hepatotoxicity Gastrointestinal Effects Seizures QTc Prolongation Anaphylactic/Allergic Reactions Most common adverse reactions (≥5%) include: nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash.

Table 5 includes clinically significant drug interactions with buprenorphine transdermal system. Table 5: Clinically Significant Drug Interactions with Buprenorphine Transdermal System Benzodiazepines Clinical Impact: There have been a number of reports regarding coma and death associated with the misuse and abuse of the combination of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection of crushed buprenorphine tablets. Preclinical studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Intervention: Regularly evaluate patients with concurrent use of buprenorphine transdermal system and benzodiazepines.

Store at 25°C (77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). Store buprenorphine transdermal system securely and dispose of properly.