Drug Interaction Report

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monitoring for the development of adverse effects may be appropriate for some drugs whenever resmetirom is added to or withdrawn from therapy.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.

ADJUST DOSING INTERVAL: Food may significantly increase the oral bioavailability of some formulations of abiraterone acetate. Compared to administration in the fasted state, abiraterone peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat; 300 calories) and approximately 17- and 10-fold higher, respectively, when it was administered with a high-fat meal (57% fat; 825 calories). Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures. The safety of these increased exposures during multiple dosing has not been assessed. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, was found to have an approximately 6.5-fold higher Cmax and 4.4-fold higher AUC when a single dose of 500 mg (4 tablets) was administered with a high-fat meal (56% - 60% fat, 900 - 1000 calories) compared to overnight fasting in healthy volunteers. These differences were not considered clinically significant for this formulation.

MANAGEMENT: Some formulations of abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least two hours before and one hour after the abiraterone acetate dose. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, can be taken with or without food. The manufacturer's product labeling should be consulted for specific guidance.