|
Sovaldi treatment should be initiated and monitored by a physician experienced in the management of patients with CHC.
Posology
The recommended dose is one 400 mg tablet, taken orally, once daily with food (see section 5.2).
Sovaldi should be used in combination with other medicinal products. Monotherapy of Sovaldi is not recommended (see section 5.1). Refer also to the Summary of Product Characteristics of the medicinal products that are used in combination with Sovaldi. The recommended co-administered medicinal product(s) and treatment duration for Sovaldi combination therapy are provided in Table 1.
Table 1: Recommended co-administered medicinal product(s) and treatment duration for Sovaldi combination therapy
|
Patient population*
|
Treatment
|
Duration
|
|
Patients with genotype 1, 4, 5 or 6 CHC
|
Sovaldi + ribavirin + peginterferon alfa
|
12 weeksa, b
|
|
Sovaldi + ribavirin
Only for use in patients ineligible or intolerant to peginterferon alfa (see section 4.4)
|
24 weeks
|
|
Patients with genotype 2 CHC
|
Sovaldi + ribavirin
|
12 weeksb
|
|
Patients with genotype 3 CHC
|
Sovaldi + ribavirin + peginterferon alfa
|
12 weeksb
|
|
Sovaldi + ribavirin
|
24 weeks
|
|
Patients with CHC awaiting liver transplantation
|
Sovaldi + ribavirin
|
Until liver transplantationc
|
* Includes patients co-infected with human immunodeficiency virus (HIV).
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, moderate or severe hepatic impairment (Child-Pugh-Turcotte [CPT] class A, B or C) (see section 5.2). The safety and efficacy of Sovaldi have not been established in patients with decompensated cirrhosis.
Patients awaiting liver transplantation
The duration of administration of Sovaldi in patients awaiting liver transplantation should be guided by an assessment of the potential benefits and risks for the individual patient (see section 5.1).
Paediatric population
The safety and efficacy of Sovaldi in children and adolescents aged <18 years have not yet been established. No data are available.
Method of administration
The film-coated tablet is for oral use. Patients should be instructed to swallow the tablet whole. The film-coated tablet should not be chewed or crushed, due to the bitter taste of the active substance. The tablet should be taken with food (see section 5.2).
Patients should be instructed that if vomiting occurs within 2 hours of dosing an additional tablet should be taken. If vomiting occurs more than 2 hours after dosing, no further dose is needed. These recommendations are based on the absorption kinetics of sofosbuvir and GS-331007 suggesting that the majority of the dose is absorbed within 2 hours after dosing.
If a dose is missed and it is within 18 hours of the normal time, patients should be instructed to take the tablet as soon as possible and then patients should take the next dose at the usual time. If it is after 18 hours then patients should be instructed to wait and take the next dose at the usual time. Patients should be instructed not to take a double dose.
|
