Drug Interaction Report

ADJUST DOSE: Coadministration with ticagrelor may increase the plasma concentrations of rosuvastatin. The proposed mechanism is inhibition of breast cancer resistance protein (BCRP) efflux transporter in the gut wall by ticagrelor, resulting in increased absorption and bioavailability of rosuvastatin. In 9 healthy volunteers, administration of a single 10 mg dose of rosuvastatin during treatment with ticagrelor 90 mg given every 12 hours for 2 days increased rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.6-fold each and prolonged its half-life from 3.1 to 6.6 hours compared to administration with placebo. Myopathy and rhabdomyolysis, including fatal cases, have occurred in patients taking ticagrelor and rosuvastatin at dosages ranging from 20 to 40 mg daily, with onset of 2 weeks to 8 months after being on both medications.

MANAGEMENT: When concomitant use of ticagrelor is required, the lowest possible starting dosage or a reduction in the existing dosage of rosuvastatin should be considered. Some authorities recommend not exceeding 10 mg/day of rosuvastatin when prescribed with ticagrelor. Alternatively, a different HMG-CoA reductase inhibitor that is not a substrate for BCRP (e.g., pitavastatin, pravastatin) may be considered. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Rosuvastatin should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.