rease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi and thus should not be used with Sovaldi (see section 4.4). Co-administration of Sovaldi with medicinal products that inhibit P-gp and/or BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration, thus Sovaldi 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 section 5.2).
Other interactions
Drug interaction information for Sovaldi with potential concomitant medicinal products is summarised in Table 3 below (where 90% confidence interval (CI) 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.
Table 3: Interactions between Sovaldi and other medicinal products
Medicinal product by therapeutic areas
Effects on drug levels.
Mean ratio (90% confidence interval) for AUC, Cmax, Cmina,b
Recommendation concerning co-administration with Sovaldi
ANALEPTICS
Modafinil
Interaction not studied.
Expected:
↓ Sofosbuvir
↓ GS-331007
Co-administration of Sovaldi with modafinil is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended.
ANTICONVULSANTS
Carbamazepine
Phenytoin
Phenobarbital
Oxcarbazepine
Interaction not studied.
Expected:
↓ Sofosbuvir
↓ GS-331007
Co-administration of Sovaldi with carbamazepine, phenytoin, phenobarbital or oxcarbazepine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended.
Sovaldi should not be used with carbamazepine, phenytoin, phenobarbital or oxcarbazepine, potent intestinal P-gp inducers (see section 4.4).
ANTIMYCOBACTERIALS
Rifabutin
Rifampicin
Rifapentine
Interaction not studied.
Expected:
↓ Sofosbuvir
↓ GS-331007
Co-administration of Sovaldi with rifabutin or rifapentine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended.
Sovaldi should not be used with rifampicin, a potent intestinal P-gp inducer (see section 4.4).
HERBAL SUPPLEMENTS
St. John's wort
(Hypericum perforatum)
Interaction not studied.
Expected:
↓ Sofosbuvir
↓ GS-331007
Sovaldi should not be used with St. John's wort, a potent intestinal P-gp inducer (see section 4.4).
HCV ANTIVIRAL AGENTS: HCV PROTEASE INHIBITORS
Boceprevir (BOC)
Telaprevir (TPV)
Intera
