Drug Interactions between buprenorphine and phenobarbital

MONITOR CLOSELY: Concomitant use of buprenorphine with other central nervous system (CNS) depressants has been associated with increased risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many involved abuse or misuse of buprenorphine including intravenous self-injection with concomitant use of benzodiazepines or alcohol. The exact mechanism of interaction is unknown, but preclinical studies suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists.

MANAGEMENT: Extreme caution is advised when prescribing buprenorphine in conjunction with other CNS depressants, or when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. Dosage reduction of CNS depressants, buprenorphine, or both should be considered if concomitant use is necessary.

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4, including certain anticonvulsants such as carbamazepine, phenobarbital, phenytoin and primidone, may decrease the plasma concentrations of buprenorphine, which is primarily metabolized by the isoenzyme. Reduced efficacy or withdrawal symptoms may occur in patients maintained on buprenorphine.

MANAGEMENT: Pharmacologic response to buprenorphine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the buprenorphine dosage adjusted as necessary.