Drug-Drug Interactions of Methadone

Antiretroviral drugs Methadone is often used for opioid replacement therapy in intravenous drug abusers. The incidence of HIV infection is significantly higher in this population than in the general public, and interactions with drugs used for the treatment of AIDS are therefore important. Methadone is predominantly metabolized by CYP3A4. Antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (for example efavirenz, abacavir, and nevirapine) and/or a protease inhibitor (for example amprenavir) will induce the metabolism of methadone. This therapeutic combination is becoming increasingly common in HIV-positive substance misusers. Two studies have explicitly shown a significant reduction of methadone concentration by 28-87%. In the first study, 11 patients taking methadone maintenance therapy were given efavirenz and had a mean increase in methadone dosage requirement of 22%. In the second study, five methadone-maintained opioid-dependent individuals were given a combination of abacavir and amprenavir; the methadone concentration fell to 35% of the original concentration within 14 days. In a prospective study of 54 patients taking antiretroviral drugs who also took methadone and a further Read more […]

Drug-Drug Interactions of Cannabinoids

Alcohol Additive psychoactive effects sought by users may be achieved by combinations of cannabis and alcohol, but at the same time the ability of THC to induce microsomal enzymes will increase the rate of metabolism of alcohol and so reduce the additive effects. Anticholinergic drugs The anticholinergic effects of cannabis may result in interactions with other drugs with anticholinergic effects, such as some antidysrhythmic drugs. Barbiturates, short-acting Additive psychoactive effects sought by users may be achieved by combinations of cannabis and short-acting barbiturates, but at the same time the ability of THC to induce microsomal enzymes will increase the rate of metabolism of barbiturates and so reduce the additive effects. Disulfiram Concurrent administration with disulfiram is associated with hypomania. Indinavir The effects of smoked marijuana (3.95% tetrahydrocan-nabinol; up to three cigarettes per day) and oral dronabi-nol (2.5 mg tds) on the pharmacokinetics of indinavir 800 mg 8-hourly (n =28) have been evaluated in a randomized, placebo-controlled study in HIV-infected patients. On day 14, marijuana reduced the 8-hour AUC of indinavir by 15%, the Cmax by 14%, and the Cmin by 34%. However, only Read more […]