Drug Interaction Report

GENERALLY AVOID: Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450 3A4, CYP450 2B6, and CYP450 1A2 isoenzymes and increase their systemic concentrations. The proposed mechanism is high and prolonged systemic exposure to the metabolite abametapir carboxyl, which has been shown to be an in vitro inhibitor of CYP450 3A4, CYP450 2B6, and CYP450 1A2. The mean half-life of abametapir carboxyl in adults is estimated to be 71 hours or longer.

MANAGEMENT: Use of CYP450 3A4, CYP450 2B6, and CYP450 1A2 substrates should generally be avoided within 2 weeks after topical application of abametapir lotion. If this is not feasible, the manufacturer recommends avoiding use of abametapir lotion. If abametapir is used, monitor for increased toxicity of the CYP450 3A4, CYP450 2B6, and/or CYP450 1A2 substrate.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.