a. For previously treated patients with HCV genotype 1 infection, no data exists with the combination of Sovaldi, ribavirin and peginterferon alfa (see section 4.4).

b. Consideration should be given to potentially extending the duration of therapy beyond 12 weeks and up to 24 weeks; especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (e.g. advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype, prior null response to peginterferon alfa and ribavirin therapy).

c. See Special patient populations – Patients awaiting liver transplantation below.

The dose of ribavirin, when used in combination with Sovaldi, is weight-based (<75 kg = 1,000 mg and ≥75 kg = 1,200 mg) and administered orally in two divided doses with food.

Concerning co-administration with other direct-acting antivirals against HCV, see section 4.4.

Dose modification

Dose reduction of Sovaldi is not recommended.

If sofosbuvir is used in combination with peginterferon alfa, and a patient has a serious adverse reaction potentially related to this drug, the peginterferon alfa dose should be reduced or discontinued. Refer to the peginterferon alfa Summary of Product Characteristics for additional information about how to reduce and/or discontinue the peginterferon alfa dose.

If a patient has a serious adverse reaction potentially related to ribavirin, the ribavirin dose should be modified or discontinued, if appropriate, until the adverse reaction abates or decreases in severity. Table 2 provides guidelines for dose modifications and discontinuation based on the patient's haemoglobin concentration and cardiac status.

Table 2: Ribavirin dose modification guideline for co-administration with Sovaldi

Laboratory values
 Reduce ribavirin dose to 600 mg/day if:
 Discontinue ribavirin if:
 
Haemoglobin in subjects with no cardiac disease
 <10 g/dL
 <8.5 g/dL
 
Haemoglobin in subjects with history of stable cardiac disease
 ≥2 g/dL decrease in haemoglobin during any 4 week period treatment
 <12 g/dL despite 4 weeks at reduced dose
 
Once ribavirin has been withheld due to either a laboratory abnormality or clinical manifestation, an attempt may be made to restart ribavirin at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that ribavirin be increased to the original assigned dose (1,000 mg to 1,200 mg daily).

Discontinuation of dosing

If the other medicinal products used in combination with Sovaldi are permanently discontinued, Sovaldi should also be discontinued (see section 4.4).

Special patient populations

Elderly

No dose adjustment is warranted for elderly patients (see section 5.2).

Renal impairment

No dose adjustment of Sovaldi is required for patients with mild or moderate renal impairment. The safety and appropriate dose of Sovaldi have not been established in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis (see section 5.2).

Hepatic impairment

No dose adjustment of Sovaldi is required for patients with mild, mode