Sofosbuvir drug interactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Drug Interactions
Potential for Drug Interactions
After oral administration of SOVALDI, sofosbuvir is rapidly converted to the predominant circulating metabolite GS-331007 that accounts for greater than 90% of drug related material systemic exposure, while the parent sofosbuvir accounts for approximately 4% of drug related material [See Clinical Pharmacology (12.3)]. 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. Drugs that are potent P-gp inducers in the intestine (e.g., rifampin or St. John's wort) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of SOVALDI and thus should not be used with SOVALDI [See Warnings and Precautions (5.2)]. Coadministration of SOVALDI with drugs that inhibit P-gp and/or BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration; accordingly, SOVALDI may be coadministered 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 drugs 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 drugs [See Clinical Pharmacology (12.3)].
Potentially Significant Drug Interactions
Drug interaction information for SOVALDI with potential concomitant drugs is summarized in Table 5. The drug interactions described are based on potential drug interactions that may occur with SOVALDI. The table is not all-inclusive [See Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].
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Drugs without Clinically Significant Interactions with SOVALDI
In addition to the drugs included in Table 5, the interaction between SOVALDI and the following drugs was evaluated in clinical trials and no dose adjustment is needed for either drug [See Clinical Pharmacology (12.3)]: cyclosporine, darunavir/ritonavir, efavirenz, emtricitabine, methadone, raltegravir, rilpivirine,tacrolimus, or tenofovir disoproxil fumarate.[1]
References
- ↑ "SOVALDI (SOFOSBUVIR) TABLET, FILM COATED [GILEAD SCIENCES, INC.]". Retrieved 7 January 2014.
Adapted from the FDA Package Insert.