SOVALDI Film-coated tablet Ref.[7098] Active ingredients: Sofosbuvir

Sovaldi treatment should be initiated and monitored by a physician experienced in the management of patients with CHC.

Posology

The recommended dose of Sovaldi in adults is one 400 mg tablet, taken orally, once daily with food (see section 5.2).

The recommended dose of Sovaldi in paediatric patients aged 3 years and above is based on weight (as detailed in Table 2). Sovaldi should be taken with food (see section 5.2).

Sovaldi oral granules are available for the treatment of chronic HCV-infection in paediatric patients aged 3 years and above having difficulty in swallowing film-coated tablets. Please refer to the Summary of Product Characteristics for Sovaldi 150 mg or 200 mg granules.

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 adults and paediatric patients treated with Sovaldi combination therapy:

^* 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 Adults: weight-based ribavirin (<75 kg = 1,000 mg and ≥75 kg = 1,200 mg); administered orally in two divided doses with food.
^d See Table 2 for weight-based Sovaldi dosing recommendations for paediatric patients aged 3 years and above.
^e See Table 3 for weight-based ribavirin dosing recommendations for paediatric patients aged 3 years and above.
^f See Special patient populations – Patients awaiting liver transplantation below.

Table 2. Dosing for paediatric patients aged 3 years and above using Sovaldi tablets*:

^* Sovaldi is also available as granules for use in paediatric patients with CHC aged 3 years and above (see section 5.1). Patients that weigh <17 kg are not recommended to take tablets. Please refer to the Summary of Product Characteristics for Sovaldi 150 mg or 200 mg granules.

In paediatric patients aged 3 years and above the following ribavirin dosing is recommended where ribavirin is divided into two daily doses and given with food:

Table 3. Guidance for ribavirin dosing when administered in combination with Sovaldi to HCV-infected paediatric patients aged 3 years and above:

^* The daily dosage of ribavirin is weight-based and is administered orally in two divided doses with food.

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

Dose modification in adults

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 medicinal product, 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 4 provides guidelines for dose modifications and discontinuation based on the patient’s haemoglobin concentration and cardiac status.

Table 4. Ribavirin dose modification guideline for co-administration with Sovaldi in adults:

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).

Dose modification in paediatric patients aged 3 years and above

Dose reduction of Sovaldi is not recommended.

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. Refer to the ribavirin prescribing information for guidance on dose modification or discontinuation.

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).

Vomiting and missed doses

Patients should be instructed that if vomiting occurs within 2 hours of dosing an additional dose 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 dose 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.

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. Safety data are limited in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²) and end stage renal disease (ESRD) requiring haemodialysis. Sovaldi can be used in these patients with no dose adjustment when no other relevant treatment options are available (see section 4.4, 4.8, 5.1 and 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).

Adult liver transplant recipients

Sovaldi in combination with ribavirin is recommended for 24 weeks in liver transplant recipients. In adults a starting ribavirin dose of 400 mg administered orally in two divided doses with food is recommended. If the starting dose of ribavirin is well-tolerated, the dose can be titrated up to a maximum of 1,000-1,200 mg daily (1,000 mg for patients weighing <75 kg and 1,200 mg for patients weighing ≥75 kg). If the starting dose of ribavirin is not well-tolerated, the dose should be reduced as clinically indicated based on haemoglobin levels (see section 5.1).

Paediatric population aged <3 years

The safety and efficacy of Sovaldi in children aged <3 years have not yet been established. No data are available.

Method of administration

Oral use.

Patients should be instructed to swallow the tablet(s) whole. The film-coated tablet(s) should not be chewed or crushed, due to the bitter taste of the active substance. The tablet(s) should be taken with food (see section 5.2).

The highest documented dose of sofosbuvir was a single supratherapeutic dose of sofosbuvir 1,200 mg administered to 59 healthy subjects. In that study, there were no untoward effects observed at this dose level, and adverse reactions were similar in frequency and severity to those reported in the placebo and sofosbuvir 400 mg treatment groups. The effects of higher doses are unknown.

No specific antidote is available for overdose with Sovaldi. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with Sovaldi consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Haemodialysis can efficiently remove (53% extraction ratio) the predominant circulating metabolite GS-331007. A 4-hour haemodialysis session removed 18% of the administered dose.

6 years.

This medicinal product does not require any special storage conditions.

Sovaldi 400 mg tablets are supplied in high density polyethylene (HDPE) bottles with a polypropylene child-resistant closure containing 28 film-coated tablets with a silica gel desiccant and polyester coil.

Sovaldi 200 mg tablets are supplied in high density polyethylene (HDPE) bottles with a polypropylene child-resistant closure containing 28 film-coated tablets and a polyester coil.

The following pack sizes are available:

• outer cartons containing 1 bottle of 28 film-coated tablets
• and for the 400 mg tablets only; outer cartons containing 84 (3 bottles of 28) film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.