Metabolic substrate

Ledipasvir : P-gp and BCRP; primarily excreted (>98%) unchanged in the feces, with little renal excretion, P-gp / Sofosbuvir : P-gp and BCRP; rapidly converted to the predominant circulating metabolite GS-331007 that accounts for greater than 90% of drug related material systemic exposure.

Metabolic inducer

–

Metabolic inhibitor

Ledipasvir : P-gp and BCRP (intestinal weak), OATP1B1/1B3, BSEP and UGT1A1 (hepatic only at doses higher than those obtained in the clinic)

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Metabolic substrate

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.

Metabolic inducer

–

Metabolic inhibitor

3A4 (weak), OATP1B1 and P-gp.

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

A reduction in dosage may be necessary.

Monitor closely.

Alternative solution(s)

–