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Sofosbuvir / Velpatasvir may inhibit P-gp and OATP1B1/3 and increase plasma concentration of Atorvastatin.
Sofosbuvir : P-gp, BCRP / Velpastasvir : P-gp, BCRP, OATP1B1/1B3, CYP 2B6, 2C8, 3A4 (in vitro)
Velpastasvir : P-gp, BCRP, OATP1B1/1B3
3A4 (major), 2C8 (minor): metabolised in acid derivatives 2-hydroxy-atorvastatin and 4-hydroxy-atorvastatin. These active metabolites are responsable of about 70% of the inhibitory activity of HMG-CoA reductase circulating. OATP1B1 and P-gp.
3A4 (weak), OATP1B1 and P-gp.
Possible increase of adverse effects.
Use this combination with caution.
A reduction in dosage may be necessary.
Monitor closely for adverse effects.
Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.
Ref #3366 : Metabolites of atorvastatin also increased: o-hydroxyatorvastatin AUC +37% and Cmax +11%; P-hydroxyatorvastatin AUC +77% and Cmax +41%; Atorvastatin lactone AUC +60% and Cmax +82%.
Exposures of sofosbuvir and its metabolites and velpatasvir were similar to historical data.
All treatments were well tolerated.