Drug Interactions between ivacaftor / lumacaftor and trimethoprim

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.