Drug Interaction Report

MONITOR: Coadministration with resmetirom may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of the CYP450 2C8 isoenzyme. The proposed mechanism, based on in vitro and clinical data, is decreased clearance due to weak inhibition of CYP450 2C8 by resmetirom. In healthy study subjects, when a single dose of the CYP450 2C8 substrate pioglitazone (15 mg) was administered with resmetirom at steady state concentrations (100 mg daily), a 1.5-fold increase in pioglitazone systemic exposure (AUC) was observed. However, the peak plasma concentration (Cmax) of pioglitazone was unchanged.

MANAGEMENT: Caution and clinical monitoring is recommended if resmetirom is coadministered with drugs that are substrates of the CYP450 2C8 isoenzyme. Dosage adjustments as well as closer clinical and laboratory monitoring for the development of adverse effects may be appropriate for some drugs whenever resmetirom is added to or withdrawn from therapy. Individual product labeling should be consulted for further guidance.

CONTRAINDICATED: Consumption of ethanol during treatment with disulfiram may cause flushing, nausea, blurred vision, dyspnea, tachypnea, tachycardia, and hypotension. Death has been reported. The mechanism is probably related to inhibition of aldehyde dehydrogenase, the enzyme responsible for the oxidation of acetaldehyde to acetyl CoA. Accumulation of acetaldehyde probably results.

MANAGEMENT: Ethanol should be avoided in patients receiving disulfiram.