MyHep Drug Interactions

Sofosbuvir is a nucleotide prodrug. After oral administration of Sofosbuvir, sofosbuvir is rapidly absorbed and subject to extensive first-pass hepatic and intestinal metabolism. Intracellular hydrolytic prodrug cleavage catalysed by enzymes including carboxylesterase 1 and sequential phosphorylation steps catalysed by nucleotide kinases result in formation of the pharmacologically active uridine nucleoside analogue triphosphate. The predominant inactive circulating metabolite GS-331007 that accounts for greater than 90% of drug-related material systemic exposure is formed through pathways sequential and parallel to formation of active metabolite. The parent sofosbuvir accounts for approximately 4% of drug-related material systemic exposure (see Pharmacology: Pharmacokinetics under Actions). In clinical pharmacology studies, both sofosbuvir and GS-331007 were monitored for purposes of pharmacokinetic analyses.
Sofosbuvir is a substrate of drug transporter P-gp and breast cancer resistance protein (BCRP) while GS-331007 is not.
Medicinal products that are potent P-gp inducers in the intestine (rifampicin, rifabutin, St. John's wort, carbamazepine, phenobarbital and phenytoin) may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sofosbuvir and thus are contraindicated with Sofosbuvir (see Contraindications). Medicinal products that are moderate P-gp inducers in the intestine (e.g. oxcarbazepine and modafinil) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sofosbuvir. Co-administration with such medicinal products is not recommended with Sofosbuvir (see Precautions). Co-administration of Sofosbuvir with medicinal products that inhibit P-gp and/or BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration, thus Sofosbuvir may be co-administered with P-gp and/or BCRP inhibitors. Sofosbuvir and GS-331007 are not inhibitors of P-gp and BCRP and thus are not expected to increase exposures of medicinal products that are substrates of these transporters.
The intracellular metabolic activation pathway of sofosbuvir is mediated by generally low affinity and high capacity hydrolase and nucleotide phosphorylation pathways that are unlikely to be affected by concomitant medicinal products (see Pharmacology: Pharmacokinetics under Actions).
Other interactions: Drug interaction information for Sofosbuvir with potential concomitant medicinal products is summarised in Table 4 (where 90% confidence interval (Cl) of the geometric least-squares mean (GLSM) ratio were within "↔", extended above "↑", or extended below "↓" the predetermined equivalence boundaries). The table is not all-inclusive. (See Table 4.)


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