Drug Interactions between pravastatin and Viekira XR

ADJUST DOSE: Coadministration with ombitasvir/paritaprevir/ritonavir plus dasabuvir may significantly increase the plasma concentrations of pravastatin. The mechanism may involve inhibition of OATP1B1-mediated hepatic uptake of pravastatin by both paritaprevir and ritonavir. In 12 study subjects, administration of pravastatin 10 mg once daily in combination with once daily morning doses of ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg) plus twice daily doses of dasabuvir resulted in increases of approximately 37% and 82% in mean pravastatin peak plasma concentration (Cmax) and systemic exposure (AUC), respectively. 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. Pravastatin had no significant effect on the pharmacokinetics of ombitasvir, paritaprevir, ritonavir, and dasabuvir.

MANAGEMENT: The benefits of using pravastatin with ombitasvir/paritaprevir/ritonavir plus dasabuvir should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. If coadministration is required, the lowest effective dosage of pravastatin should be used and close monitoring for musculoskeletal toxicity is recommended. The dosage of pravastatin should be limited to 40 mg/day. Alternatively, an interruption of pravastatin may be considered during treatment with ombitasvir/paritaprevir/ritonavir plus dasabuvir, or a different HMG-CoA reductase inhibitor such as fluvastatin or pitavastatin may be substituted. 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.

MONITOR: Coadministration with ritonavir may decrease the plasma concentrations of pravastatin. The proposed mechanism is ritonavir induction of pravastatin metabolism via glucuronosyl transferase. In 13 healthy volunteers, the combination of ritonavir (300 mg twice a day for 3 days, then 400 mg twice a day) and saquinavir (soft gelatin capsule 400 mg twice a day) given for 14 days decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of pravastatin (40 mg once a day for 4 days) by 42% and 50%, respectively. The clinical relevance of these changes is unknown. Pravastatin appeared to have no significant effect on the plasma levels of ritonavir and saquinavir based on comparison with historical controls. It is not known to what extent, if any, the interaction may occur when ritonavir is used in lower dosages as a pharmacokinetic booster. No interaction was observed when pravastatin was given with lopinavir-ritonavir in drug interaction studies.

MANAGEMENT: Pravastatin appears to be safe when coadministered with ritonavir, although the potential for diminished hypolipidemic efficacy should be considered when antiretroviral dosages of ritonavir is prescribed. Pharmacologic response to pravastatin should be monitored more closely whenever ritonavir is added to or withdrawn from therapy, and the pravastatin dosage adjusted as necessary.