Co-administration with other direct-acting antivirals against HCV

Sovaldi should only be co-administered with other direct-acting antiviral medicinal products if the benefit is considered to outweigh the risks based upon available data. There are no data to support the co-administration of Sovaldi and telaprevir or boceprevir. Such co-administration is not recommended (see also section 4.5).

Pregnancy and concomitant use with ribavirin

When Sovaldi is used in combination with ribavirin or peginterferon alfa/ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and for a period of time after the treatment as recommended in the Summary of Product Characteristics for ribavirin. Refer to the Summary of Product Characteristics for ribavirin for additional information.

Use with potent P-gp inducers

Medicinal products that are potent P-glycoprotein (P-gp) inducers in the intestine (e.g. rifampicin, St. John's wort [Hypericum perforatum], carbamazepine and phenytoin) may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi. Such medicinal products should not be used with Sovaldi (see section 4.5).

Renal impairment

The safety of Sovaldi has not been assessed in subjects with severe renal impairment (eGFR <30 mL/min/1.73 m2) or ESRD requiring haemodialysis. Furthermore, the appropriate dose has not been established. When Sovaldi is used in combination with ribavirin or peginterferon alfa/ribavirin, refer also to the Summary of Product Characteristics for ribavirin for patients with creatinine clearance (CrCl) <50 mL/min (see also section 5.2).

HCV/HBV (hepatitis B virus) co-infection

There are no data on the use of Sovaldi in patients with HCV/HBV co-infection.

Paediatric population

Sovaldi is not recommended for use in children and adolescents under 18 years of age because the safety and efficacy have not been established in this population.

4.5 Interaction with other medicinal products and other forms of interaction
 Sofosbuvir is a nucleotide prodrug. After oral administration of Sovaldi, 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 section 5.2). 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 (e.g. rifampicin, St. John's wort, carbamazepine and phenytoin) may dec