Drug Interactions between eltrombopag and Lescol XL

ADJUST DOSE: Coadministration with eltrombopag may increase the plasma concentrations of HMG-CoA reductase inhibitors (statins). The proposed mechanism is decreased clearance due to eltrombopag inhibition of the OATP 1B1-mediated hepatic uptake of statins and/or their metabolites (e.g., simvastatin acid), with fluvastatin the least likely to be significantly affected. In 39 healthy adult subjects given eltrombopag 75 mg once daily for 4 days prior to coadministration with a single 10 mg dose of rosuvastatin on day 5, mean rosuvastatin peak plasma concentration (Cmax) increased by 103% and systemic exposure (AUC) by 55%. High levels of HMG-CoA reductase inhibitory activity in plasma is 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: Lower statin dosages should be considered during coadministration with eltrombopag. In clinical trials with eltrombopag, a dosage reduction of rosuvastatin by 50% was recommended. No specific adjustment recommendations were given for the others. 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.

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