Coadministration of bupropion (150 mg single dose, sustained release) and efavirenz (600 mg once daily) decreased bupropion AUC and Cmax by 55% and 34% , respectively, with a 50% increase in Cmax of hydroxybupropion and no change in AUC (CYP2B6 induction). Increases in bupropion dosage should be guided by clinical response, but the maximum recommended dose of bupropion should not be exceeded. No dose adjustment is necessary for efavirenz.

Coadministration of bupropion (150 mg single dose, sustained release) and efavirenz (600 mg once daily) to 13 subjects decreased bupropion Cmax and AUC by 34% and 55%, respectively. There was a 50% increase in Cmax of hydroxybupropion, but no change in AUC. The effect of efavirenz on bupropion exposure is thought to be due to the induction of bupropion metabolism. Increases in bupropion dosage should be guided by clinical response, but the maximum recommended dose of bupropion should not be exceeded.

Coadministration of efavirenz (600 mg once daily) and bupropion (150 mg single dose) was studied in 13 HIV- subject to assess the effect of efavirenz on CYP2B6 activity. Bupropion AUC and Cmax decreased by 55% and 34%, respectively. The AUC of a pharmacologically active metabolite, hydroxybupropion, was unchanged, but half life decreased from 24 h to 16 h. The 55% decrease in bupropion exposure may be clinically significant in patients on efavirenz taking bupropion as an aid for smoking cessation or as an antidepressant.

Bupropion metabolism is mediated primarily by CYP2B6 and in vitro data has pointed to nelfinavir, ritonavir and efavirenz being inhibitors of this enzyme. There is therefore potential for a drug interaction. This report is a case series aimed at documenting the clinical consequence of the co-administration of bupropion with nelfinavir, ritonavir, and efavirenz. The median duration of concomitant use was 8 months and ranged from 3 weeks to 2 years. There were no episodes of seizures documented in any of the medical records for patients who took bupropion with the CYP2B6 inhibitors. However, these data should be regarded as highly preliminary since: there is a low rate of seizure incidence in the literature, There were no PK measurements which are vital if we are to understand this interaction and no patients were receiving ritonavir at a dose above 100 mg bd. Further data are therefore required.

The hydroxylation of bupropion was studied in vitro using human liver microsomes. It was concluded that ritonavir, efavirenz and nelfinavir inhibited CYP2B6 and therefore bupropion hydroxylation. The IC50 for efavirenz was 5.5 µM. This suggests that there is the potential for clinical drug interactions.