Drug Interactions between dimethyl fumarate and SMZ-TMP DS

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 does not significantly affect the oral bioavailability of dimethyl fumarate. Administration of dimethyl fumarate with a high-fat, high-calorie meal did not affect the systemic exposure (AUC) to its active metabolite, monomethyl fumarate (MMF), but decreased its peak plasma concentration (Cmax) by 40% and prolonged the time to reach peak concentration (Tmax) from 2.0 hours to 5.5 hours. In the study, the incidence of flushing was reduced by approximately 25% in the fed state. Dimethyl fumarate may be taken with or without food; however, taking it with food may help reduce flushing.