Is there any risk of an interaction between methadone and Zyban (bupropion)?/nA 49-year-old drug ad

Fråga: Is there any risk of an interaction between methadone and Zyban (bupropion)?

A 49-year-old drug addicted woman with hepatitis and HIV infection is currently undergoing treatment with methadone and is planned to start bupropion treatment. She has normal liver function and is not taking any other drugs.

Sammanfattning: We found no reports of an interaction between methadone and bupropion. Theoretically, a pharmacokinetic drug interaction between them is possible, although the clinical significance of such an interaction is probably low.

Therapeutic drug monitoring of methadone should be considered if untoward adverse events arise.

Svar: In a literature search through Medline, Embase, Drugline and standard pharmacological textbooks, we found no reports of drug interaction between methadone and bupropion.

Bupropion is metabolised by CYP2B6, CYP1A2 and CYP3A4. Bupropion and its active metabolite, hydroxybupropion are both inhibitors of CYP2D6 (1,2). Methadone is metabolised mainly by CYP3A4 with a possible involvement of CYP2C19, CYP1A2, 2C9 and 2D6 (3). Thus, bupropion and methadone can theoretically interact, but this may not have any clinical relevance since CYP2D6 is probably a minor metabolic pathway of methadone. In a multi-site, placebo controlled, randomised double blind 12-week study (4), bupropion (300 mg/day) (n=74) was compared to placebo (n=79) for the treatment of cocaine dependence in methadone-maintained subjects. Although drug interaction was not an end-point in the study, no increased frequency of adverse drug reactions was observed in those patients who received the combination of bupropion and methadone as compared to the control group. 1 FASS 2000 (The Swedish catalogue of approved medical products) 2 Drugline no 16931 (year 2000) 3 Drugline no 15979 (year 1999) 4 Margolin A, Kosten TR, Avants SK, Wilkins J, Ling W, Beckson M, Arndt IO, Cornish J, Ascher JA, Li S-H, Bridge P: A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Drug Alcohol Depend 1995; 40: 125-131