indication

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.

toxicity

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

biotransformation

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.

absorption

31% bioavailability (sublingual)

half life

37 hours

route of elimination

Buprenorphine, in common with morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow.

drug interactions

Alvimopan: Opioids like buprenorphine may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Consider therapy modification.

Atazanavir: Atazanavir may increase the serum concentration of Buprenorphine. Buprenorphine may decrease the serum concentration of Atazanavir. Avoid use of buprenorphine in patients receiving atazanavir without ritonavir boosting due to possible decreases in atazanavir exposure. In patients receiving buprenorphine with atazanavir/ritonavir, monitor for increased buprenorphine effects and consider dose reductions if patients experience adverse effects.

Conivaptan: Conivaptan may increase the serum concentration of CYP3A4 Substrates like buprenorphine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.

Droperidol: Droperidol may enhance the CNS depressant effect of CNS Depressants like buprenorphine. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

Isocarboxazid: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like isocarboxazid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Linezolid: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like linezolid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Moclobemide: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like moclobemide. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Phenelzine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like phenelzine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Procarbazine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like procarbazine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Rasagiline: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like rasagiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Selegiline: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like selegiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Telithromycin: Telithromycin may reduce clearance of Buprenorphine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Buprenorphine if Telithromycin is initiated, discontinued or dose changed.

Tranylcypromine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like tranylcypromine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Triprolidine: The CNS depressants, Triprolidine and Buprenorphine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of buprenorphine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of buprenorphine if voriconazole is initiated, discontinued or dose changed.