Drug Interaction Report

ADJUST DOSE: Coadministration with enasidenib may significantly increase the plasma concentrations of rosuvastatin. One mechanism involves inhibition of breast cancer resistance protein (BCRP) efflux transporter in the gut wall by enasidenib, resulting in increased absorption and bioavailability of rosuvastatin. A second mechanism involves enasidenib inhibition of the organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of rosuvastatin, resulting in decreased clearance. When a single 10 mg dose of rosuvastatin was administered following enasidenib 100 mg daily for 28 days in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome, mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 4.7- and 3.4-fold, 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: The dosage of rosuvastatin should start at 5 mg and not exceed 10 mg once daily when used in combination with enasidenib. 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.