Drug Interaction Report

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 2C8 may significantly increase the plasma concentrations of resmetirom, which is primarily metabolized by the isoenzyme. When clopidogrel, a moderate CYP450 2C8 inhibitor, was administered concomitantly with multiple doses of resmetirom (100 mg daily) to study subjects, resmetirom peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3-fold and 1.7-fold, respectively. The risk of adverse effects such hepatotoxicity, gallbladder-related adverse reactions, diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness may be increased.

MANAGEMENT: When concomitant use with a moderate CYP450 2C8 inhibitor is required, the manufacturer recommends reducing the dose of resmetirom. For patients <100 kg, the dose should be reduced from 80 mg to 60 mg daily; for patients >/= 100 kg, the dose should be reduced from 100 mg to 80 mg daily. Closer monitoring for adverse effects is advised following initiation of treatment with moderate CYP450 2C8 inhibitors.