Active Ingredient: Sofosbuvir
Sofosbuvir is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 400 milligrams sofosbuvir, once daily to meals.
The recommended dose is 400 mg, taken orally, once daily with food.
Sofosbuvir should be used in combination with other medicinal products. Monotherapy of sofosbuvir is not recommended. Refer also to the Summary of Product Characteristics of the medicinal products that are used in combination with sofosbuvir. The recommended co-administered medicinal product(s) and treatment duration for sofosbuvir combination therapy are provided in Table 1.
Table 1. Recommended co-administered medicinal product(s) and treatment duration for adults treated with sofosbuvir combination therapy:
| Patient population* | Treatment | Duration |
|---|---|---|
| Patients with genotype 1, 4, 5 or 6 CHC | sofosbuvir + ribavirin + peginterferon alfa | 12 weeksa,b |
| sofosbuvir + ribavirin. Only for use in patients ineligible or intolerant to peginterferon alfa | 24 weeks | |
| Patients with genotype 2 CHC | sofosbuvir + ribavirin | 12 weeksb |
| Patients with genotype 3 CHC | sofosbuvir + ribavirin + peginterferon alfa | 12 weeksb |
| sofosbuvir + ribavirin | 24 weeks | |
| Patients with CHC awaiting liver transplantation | sofosbuvir + ribavirin | Until liver transplantation |
* 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 sofosbuvir, ribavirin and peginterferon alfa.
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).
The dose of ribavirin, when used in combination with sofosbuvir 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.
Dose reduction of sofosbuvir 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.
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 sofosbuvir in adults:
| Laboratory values | Reduce ribavirin dose to 600 mg/day if: | Discontinue ribavirin if: |
|---|---|---|
| Haemoglobin in patients with no cardiac disease | <10 g/dL | <8.5 g/dL |
| Haemoglobin in patients with history of stable cardiac disease | ≥2 g/dL decrease in haemoglobin during any 4 week treatment period | <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).
If the other medicinal products used in combination with sofosbuvir are permanently discontinued, sofosbuvir should also be discontinued.
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.
It should be taken with food.
For:
Regimen A: In case that patient age in years is ≥ 3 and patient weight is ≤ 17 kg, oral, 150 milligrams sofosbuvir, once daily to meals.
Regimen B: In case that patient age in years is ≥ 3 and patient weight is ≥ 17 kg and patient weight is ≤ 35 kg, oral, 200 milligrams sofosbuvir, once daily to meals.
Regimen C: In case that patient age in years is ≥ 3 and patient weight is ≥ 35 kg, oral, 400 milligrams sofosbuvir, once daily to meals.
The recommended dose of sofosbuvir in paediatric patients aged 3 years and above is based on weight.
Sofosbuvir should be used in combination with other medicinal products. Monotherapy of sofosbuvir is not recommended.
Table 1. Recommended co-administered medicinal product(s) and treatment duration for paediatric patients treated with sofosbuvir combination therapy:
| Patient population* | Treatment | Duration |
|---|---|---|
| Paediatric patients aged 3 years and above with genotype 2 CHC | Sofosbuvirb + ribavirinc | 12 weeksa |
| Paediatric patients aged 3 years and above with genotype 3 CHC | Sofosbuvirb + ribavirinc | 24 weeks |
* Includes patients co-infected with human immunodeficiency virus (HIV).
a 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).
b See Table 2 for weight-based sofosbuvir dosing recommendations for paediatric patients aged 3 years and above.
c See Table 3 for weight-based ribavirin dosing recommendations for paediatric patients aged 3 years and above.
Table 2. Dosing for paediatric patients aged 3 years and above:
| Body Weight (kg) | Sofosbuvir Daily Dose |
|---|---|
| ≥35 | 400 mg/day |
| 17 to <35 | 200 mg/day |
| <17 | 150 mg/day |
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 sofosbuvir to HCV-infected paediatric patients aged 3 years and above:
| Body weight kg (lbs) | RBV daily dose* |
|---|---|
| <47 (<103) | 15 mg/kg/day |
| 47-49 (103-108) | 600 mg/day |
| 50-65 (110-143) | 800 mg/day |
| 66-80 (145-176) | 1000 mg/day |
| >81 (178) | 1200 mg/day |
* The daily dosage of ribavirin is weight-based and is administered orally in two divided doses with food.
Dose reduction of sofosbuvir 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.
If the other medicinal products used in combination with sofosbuvir are permanently discontinued, sofosbuvir should also be discontinued.
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.
Sofosbuvir should be taken with food.
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