Drug Interactions between Rezdiffra and rosuvastatin

ADJUST DOSE: Coadministration with resmetirom may increase the plasma concentrations and effects of the statins rosuvastatin and simvastatin. The proposed mechanism is decreased clearance of the statin due to resmetirom-mediated inhibition of organic anion transporting polypeptides (OATP) 1B1/1B3 and breast cancer resistance protein (BCRP). Rosuvastatin and simvastatin are substrates of OATP 1B1 and OATP 1B3; while rosuvastatin is also a substrate of BCRP. When healthy subjects taking resmetirom at steady state (at two times the highest recommended dosage) were administered a single dose of rosuvastatin (10 mg), the peak plasma concentration (Cmax) and systemic exposure (AUC) of rosuvastatin increased by 2.9 and 1.8-fold, respectively. Similarly, when healthy subjects taking resmetirom at steady state (100 mg daily) were administered a single dose of simvastatin (20 mg) the peak plasma concentration (Cmax) and systemic exposure (AUC) of increased by 1.4 and 1.7- fold, respectively. An increase in statin-related adverse effects may occur (e.g., myopathy and rhabdomyolysis).

MANAGEMENT: If concomitant use with resmetirom is required, the manufacturer advises a dose reduction of rosuvastatin and simvastatin to a maximum recommended daily dosage of 20 mg. Closer monitoring for adverse effects such as myopathy and rhabdomyolysis may also be advised. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.