Active ingredient: Buprenorphine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Narcotics
• Analgesics, Opioid
• Narcotic Antagonists

Dosage Forms

• Tablet (sublingual)

Brands / Synonyms

Buprenex; Buprenophine; Buprenorfina [Inn-Spanish]; Buprenorphine; Buprenorphine Hcl; Buprenorphinum [Inn-Latin]; Butrans; Suboxone; Subutex; Temgesic

Indications

For the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence.

Pharmacology

Buprenorphine is a synthetic opioid analgesic and thebaine derivative, with a longer duration of action than morphine. Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Buprenorphine may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Mechanism of Action

Buprenorphine's analgesic effect is due to partial agonist activity at mu-opioid receptors. Buprenorphine is also a kappa-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. The binding to the mu and kappa receptors results in hyperpolarization and reduced neuronal excitability.

Absorption

31% bioavailability (sublingual)

Toxicity

Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death.

Biotrnasformation / Drug Metabolism

Hepatic. Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation. The N-dealkylation pathway is mediated by cytochrome P-450 3A4 isozyme. Norbuprenorphine, an active metabolite, can further undergo glucuronidation.

Contraindications

SUBOXONE and SUBUTEX should not be administered to patients who have been shown to be hypersensitive to buprenorphine, and SUBOXONE should not be administered to patients who have been shown to be hypersensitive to naloxone.

Drug Interactions

Buprenorphine is metabolized to norbuprenorphine by cytochrome CYP 3A4. Because CYP 3A4 inhibitors may increase plasma concentrations of buprenorphine, patients already on CYP 3A4 inhibitors such as azole antifungals (e.g. ketoconazole), macrolide antibiotics (e.g. erythromycin), and HIV protease inhibitors (e.g. ritonavir, indi-navir and saquinavir) should have their dose of SUBUTEX or SUBOXONE adjusted.

Based on anecdotal reports, there may be an interaction between buprenorphine and benzodiazepines. There have been a number of reports in the post-marketing experience of coma and death associated with the concomitant intravenous misuse of buprenorphine and benzodiazepines by addicts. In many of these cases, buprenorphine was misused by self-injection of crushed SUBUTEX tablets. SUBUTEX and SUBOXONE should be prescribed with caution to patients on benzodiazepines or other drugs that act on the central nervous system, regardless of whether these drugs are taken on the advice of a physician or are taken as drugs of abuse. Patients should be warned of the potential danger of the intravenous self-administration of benzodiazepines while under treatment with SUBOXONE or SUBUTEX.