Drug Interactions between Harvoni and pitavastatin

MONITOR: Coadministration of HMG-CoA reductase inhibitors (statins) with HCV NS5A/NS5B inhibitors, such as ledipasvir, may significantly increase the plasma concentrations of the statin and the risk of adverse effects, such as myopathy and rhabdomyolysis. The proposed mechanism of this interaction has not been clearly delineated but may involve ledipasvir-mediated inhibition of the metabolism of statins via hepatic transport enzymes and/or CYP450 isoenzymes. This interaction has not been studied specifically with all statins; data are currently available for rosuvastatin. In 18 healthy volunteers, administration of a single 10 mg dose of rosuvastatin with velpatasvir, an HCV NS5A/NS5B inhibitor, 100 mg once daily increased mean rosuvastatin peak plasma concentration (Cmax) by approximately 2.6-fold and systemic exposure (AUC) by 2.7-fold compared to rosuvastatin administered alone. 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. It should be noted that some authorities assert that no clinically significant drug interactions have been either observed or are expected when ledipasvir is used with pravastatin (US); however, other authorities claim that ledipasvir may affect the concentration of pravastatin and increase the risk of myopathy (UK). Data are lacking.

MANAGEMENT: Caution and close monitoring are recommended if ledipasvir is used concomitantly with a statin and a dosage reduction for the statin drug considered. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, fever, malaise, and/or dark colored urine, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. 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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