Drug Interactions between resmetirom and Viekira XR

GENERALLY AVOID: Coadministration with inhibitors of the hepatic uptake transporters organic anion transporting polypeptides (OATP) 1B1 and/or OATP 1B3 may increase the plasma concentrations of resmetirom, which has been shown to be a substrate and inhibitor of these transporters in vitro. This may increase the risk and/or severity of resmetirom-related adverse effects (e.g., hepatotoxicity, gallbladder-related adverse reactions, diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, dizziness); however, clinical data are not available.

MANAGEMENT: According to the manufacturer of resmetirom, concomitant use with inhibitors of OATP 1B1 and/or OATP 1B3 should generally be avoided.

MONITOR: Coadministration with resmetirom may increase the plasma concentrations and effects of drugs that are substrates of hepatic uptake transporters organic anion transporting polypeptides (OATP) 1B1, OATP 1B3, and/or the intestinal and hepatobiliary efflux transporter breast cancer resistance protein (BCRP). Resmetirom is both a substrate and an inhibitor of these transporters. Clinical studies exist for resmetirom with OATP1B1 and OATP1B3 substrates, simvastatin, and pravastatin; as well as with rosuvastatin and atorvastatin which are BCRP, OATP1B1 and OATP1B3 substrates. Resmetirom was shown to increase the systemic exposure (AUC) of simvastatin, pravastatin, rosuvastatin, and atorvastatin by 1.7-fold, 1.4-fold, 1.8-fold, and 1.4-fold, respectively. Clinical data are not available for other OATP 1B1, OATP 1B3 and/or BCRP substrates.

MANAGEMENT: Caution and closer monitoring may be advised if resmetirom is coadministered with drugs that are substrates of the OATP 1B1, OATP 1B3, and/or BCRP transporters. Dosage adjustments as well as 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monitoring for the development of adverse effects may be appropriate for some drugs whenever resmetirom is added to or withdrawn from therapy.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.

GENERALLY AVOID: Coadministration with inhibitors of the hepatic uptake transporters organic anion transporting polypeptides (OATP) 1B1 and/or OATP 1B3 may increase the plasma concentrations of resmetirom, which has been shown to be a substrate and inhibitor of these transporters in vitro. This may increase the risk and/or severity of resmetirom-related adverse effects (e.g., hepatotoxicity, gallbladder-related adverse reactions, diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, dizziness); however, clinical data are not available.

MANAGEMENT: According to the manufacturer of resmetirom, concomitant use with inhibitors of OATP 1B1 and/or OATP 1B3 should generally be avoided.

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of dasabuvir, which is primarily metabolized by the isoenzyme. In 11 study subjects, the potent CYP450 2C8 inhibitor gemfibrozil given at 600 mg twice daily increased single-dose dasabuvir peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 2- and 11-fold, respectively. The risk of ALT elevations and QT prolongation may be increased.

MANAGEMENT: Caution is advised if dasabuvir is prescribed in combination with CYP450 2C8 inhibitors. Patients should be monitored for development of hepatotoxicity (i.e., ALT elevations) and QT interval prolongation.