Drug Interactions between letermovir and pravastatin

ADJUST DOSE: Coadministration with letermovir may increase the plasma concentrations of HMG-CoA reductase inhibitors and/or their metabolites. The proposed mechanism is reduced metabolic clearance due to inhibition of the hepatic uptake transporters, organic anion transporting polypeptide protein (OATP) 1B1 and 1B3, by letermovir. Inhibition of CYP450 3A4 and breast cancer resistance protein (BCRP) may also contribute depending on the statin. Additional use of cyclosporine is likely to further increase the magnitude of interaction, since it is a strong inhibitor of OATP 1B1 and 1B3. 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: A dosage reduction of the statin may be necessary when used with letermovir. Please refer to the statin prescribing information for specific statin dosing recommendations. 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.