Drug Interaction Report

MONITOR: Trimethoprim may decrease the renal clearance of amantadine and memantine. The mechanism may be competition for organic cation transporter-2 (OCT-2)-mediated secretion in the kidney tubule of which amantadine, memantine, and trimethoprim are substrates. Trimethoprim may also inhibit OCT-2. Increased levels of amantadine and memantine may increase the risk of neurological side effects such as mental confusion, delirium, and myoclonus. Serum trimethoprim levels may also be increased.

MANAGEMENT: Caution and monitoring for nervous system side effects is recommended if trimethoprim is used with either amantadine or memantine. Patients should be advised to contact their physician if they experience nervous system side effects such as mental confusion and myoclonus.

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.