Drug Interaction Report

ADJUST DOSE: Coadministration with glecaprevir-pibrentasvir may increase the plasma concentrations of all statins including fluvastatin and pitavastatin. The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of statins by glecaprevir and pibrentasvir. Although the interaction has not been studied specifically with fluvastatin or pitavastatin, it has been reported with other statins that are also substrates of OATP1B1. 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: Caution is advised during concomitant administration of fluvastatin or pitavastatin with glecaprevir-pibrentasvir. The lowest approved dosage of the statin should be used. If higher dosages are required, the lowest effective statin dosage should be prescribed based on a risk/benefit assessment.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.