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Omeprazole by increasing gastric pH may decrease the solubility, absorption, and plasma concentration of ledipasvir .
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.
Ledipasvir : P-gp and BCRP (intestinal weak), OATP1B1/1B3, BSEP and UGT1A1 (hepatic only at doses higher than those obtained in the clinic)
Possible decrease of clinical efficacy.
Monitor for clinical efficacy.
2C19, 2C8 3A4, 2D6
Give ledipasvir/sofosbuvir simultaneously with the proton-pump inhibitor. Proton-pump inhibitors should not be taken before taking ledipasvir/sofosbuvir.
Recommended dosage : doses comparable to omeprazole 20 mg QD either dexlansoprazole 30 mg; esomeprazole 20 mg; lansoprazole 30 mg; pantoprazole 40 mg; rabeprazole 20 mg.
|90 / 400 mg|
|- 11% / + 12% †|
|- 4% / ± 0% †|
|x 1 *|
Ref #3073 :
* Omeprazole and Oméprazole et ledipasvir/sofosbuvir taken at the same time.
† GS-331007, sofosbuvir active metabolite : AUC +3% and Cmax +14%.
In another study with ledipasvir alone, there was a 48% and 42% decrease in Cmax and AUC when ledipasvir was given 2 hours after omeprazole 20 mg.
Equivalent doses to omeprazole 20 mg: dexlansoprazole 30 mg; esomeprazole 20 mg; lansoprazole 30 mg; pantoprazole 40 mg; rabeprazole 20 mg.