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.

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.