Drug Interaction Report

GENERALLY AVOID: Coadministration with tafamidis may increase the plasma concentrations of rosuvastatin. The proposed mechanism is inhibition of intestinal and hepatic breast cancer resistance protein (BCRP) efflux transporter by tafamidis, resulting in increased oral bioavailability and reduced hepatic clearance of rosuvastatin. When a single 10 mg dose of rosuvastatin was administered following pretreatment with tafamidis (61 mg twice daily on days 1 and 2, followed by 61 mg once daily on days 3 to 9) in healthy volunteers, mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 86% and 97%, respectively, compared to administration of rosuvastatin alone. High levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: According to the prescribing information for rosuvastatin, concomitant use with tafamidis should be avoided when possible because tafamidis alone may cause myopathy and the risk may be increased in combination with rosuvastatin. If coadministration is required, the dosage of rosuvastatin should start at 5 mg and not exceed 20 mg once daily. Alternatively, a different statin that is not expected to be significantly affected by BCRP inhibition such as pitavastatin or pravastatin may be considered. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.