Drug Interaction Report

MONITOR: Coadministration with potent inducers of CYP450 2C9 and 3A4 may decrease the plasma concentrations of sulfamethoxazole and trimethoprim. A small amount of sulfamethoxazole is metabolized by CYP450 2C9, while trimethoprim is partially metabolized by both CYP450 2C9 and 3A4. In a study of 10 HIV-infected patients receiving sulfamethoxazole-trimethoprim prophylaxis (800 mg-160 mg orally once a day) for at least one month, antituberculosis therapy containing rifampin (600 mg/day) given for more than 12 days decreased mean sulfamethoxazole systemic exposure (AUC) by 23% and mean trimethoprim AUC by 47%, most likely due to induction of hepatic microsomal enzymes by rifampin. The clinical significance of this interaction is unknown, but may be greater with low dosages of sulfamethoxazole-trimethoprim. A case-control study evaluating the effect of sulfamethoxazole-trimethoprim dosage on the risk of toxoplasmosis suggest that rifampin exposure may reduce the efficacy of sulfamethoxazole-trimethoprim prophylaxis. Other potent CYP450 inducers may interact similarly.

MANAGEMENT: The potential for diminished pharmacologic effects of sulfamethoxazole-trimethoprim should be considered during coadministration with potent CYP450 2C9 and 3A4 inducers, particularly when sulfamethoxazole-trimethoprim is used for prevention of toxoplasmic encephalitis in HIV patients because adequate drug levels are required in the central nervous system. It may be advisable to refrain from low-dose prophylactic regimens (less than 4 DS tablets per week). Alternative treatments may be required if an interaction is suspected.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.