Drug Interactions between ledipasvir / sofosbuvir and ranitidine bismuth citrate

ADJUST DOSE: Coadministration of ledipasvir with H2-receptor antagonists may reduce its gastrointestinal absorption. Ledipasvir exhibits pH-dependent solubility, with increased solubility at lower pH. In 12 healthy volunteers, mean ledipasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 20% and 11%, respectively, when a single 90 mg-400 mg dose of ledipasvir-sofosbuvir was administered simultaneously with a 40 mg dose of famotidine. When the famotidine dose was given 12 hours before the ledipasvir-sofosbuvir dose, mean ledipasvir Cmax decreased by 17% and AUC decreased by just 2%. These alterations are not considered clinically significant. However, higher dosages of famotidine or another H2-receptor antagonist may result in a greater magnitude of interaction.

MANAGEMENT: H2-receptor antagonists may be administered simultaneously with or 12 hours apart from ledipasvir-sofosbuvir at a dose that does not exceed the equivalent of famotidine 40 mg twice daily.