Drug Interaction Report

In a study with 14 HIV-positive patients, coadministration of trimethoprim/sulfamethoxazole (trimethoprim/sulfamethoxazole DS once a day for 5 days) and lamivudine (300 mg single dose on day 5) resulted in a mean decrease of 35% in lamivudine renal clearance and a mean increase of 43% in lamivudine area under the plasma concentration-time curve. The mechanism of interaction is thought to be competitive inhibition of tubular secretion by trimethoprim. Lamivudine did not affect the pharmacokinetic profile of trimethoprim/sulfamethoxazole. Given the favorable safety profile of lamivudine, this interaction is unlikely to be of clinical significance. However, patients with renal dysfunction should be monitored carefully and the lamivudine dose adjusted if necessary. In addition, it should be noted that the effect of higher dosages of trimethoprim/sulfamethoxazole on lamivudine pharmacokinetics has not been investigated.

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.