What it's for (Indications)
- Sofosbuvir is a direct-acting antiviral agent used for the treatment of chronic hepatitis C virus (HCV) infection in adults and pediatric patients aged 3 years and older.
- It is effective against specific HCV genotypes, often used in combination with other antiviral agents.
- It may also be used in patients undergoing liver transplantation or those with hepatocellular carcinoma in the context of HCV infection.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | 1. **Pre-treatment Screening**: All patients must be tested for Hepatitis B Virus (HBV) infection (HBsAg and anti-HBc) prior to initiating Sofosbuvir therapy. 2. **Adults**: The recommended dosage is 400 mg once daily, taken orally with or without food. 3. **Pediatric Patients (3 years and older)**: For pediatric patients with genotype 2 or 3 HCV, the recommended dosage is weight-based. Refer to the full prescribing information for detailed pediatric dosing guidelines (e.g., specific tables for SOVALDI tablets or oral pellets). 4. **Combination Therapy**: Sofosbuvir is typically used in combination with other antiviral agents (e.g., ribavirin, peginterferon alfa, other direct-acting antivirals) for varying durations (e.g., 12 weeks) depending on HCV genotype, patient's treatment history, presence of cirrhosis, and other factors. Specific regimens should follow established guidelines. 5. **HCV/HIV-1 Coinfection**: Dosage recommendations for adult and pediatric patients with HCV/HIV-1 coinfection should follow specific guidelines provided in the full prescribing information. 6. **Renal Impairment**: For patients with severe renal impairment or end-stage renal disease, appropriate dose modifications or substitution with a viable alternative may be necessary following a thorough medical evaluation. |
Safety & Warnings
Common Side Effects
- Common adverse effects (incidence ≥ 20% in combination therapy) include fatigue, headache, nausea, insomnia, and anemia.
- In pediatric patients, decreased appetite is also common.
- Other reported side effects include blood dyscrasias (blood disorders), anorexia, weight loss, depression, anxiety, agitation, dizziness, migraine, attention disturbances, blurred vision, cough, stomach upset, and rash.
- A serious adverse reaction, symptomatic bradycardia, has been reported, particularly when Sofosbuvir is coadministered with amiodarone.
Serious Warnings
- Black Box Warning: WARNING: RISK OF HEPATITIS B VIRUS (HBV) REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV. All patients must be tested for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating treatment with Sofosbuvir. HBV reactivation, in some cases leading to fulminant hepatitis, hepatic failure, and death, has been reported in HCV/HBV coinfected patients undergoing or completing treatment with HCV direct-acting antivirals who were not receiving HBV antiviral therapy. Monitor HCV/HBV coinfected patients for HBV flare during and after treatment.
- 1.
- **Hepatitis B Virus (HBV) Reactivation**: All patients must be tested for current or prior HBV infection (HBsAg and anti-HBc) before initiating Sofosbuvir therapy due to the risk of HBV reactivation, which can lead to severe hepatic events, including fulminant hepatitis, hepatic failure, and death.
- 2.
- **Bradycardia Risk**: Coadministration of Sofosbuvir with amiodarone may lead to serious symptomatic bradycardia.
- The mechanism is unknown, and such coadministration is not recommended.
- If unavoidable, patients should be closely monitored.
- 3.
- **Renal Impairment**: Sofosbuvir should be used with caution in patients with severe renal impairment or end-stage renal disease due to an increased risk of severe side effects.
- Close monitoring of renal function and appropriate dose modification or substitution with an alternative treatment may be necessary.
- 4.
- **Pregnancy and Lactation**: Use in pregnant or lactating women should only occur if absolutely essential, after careful consideration of potential benefits and risks with a healthcare provider.
- 5.
- **Driving and Operating Machinery**: Sofosbuvir treatment may cause fatigue, concentration problems, dizziness, and vision problems, which could mildly impair the ability to drive or operate machinery.
- Patients should be advised accordingly.
- 6.
- **Diabetes**: HCV treatment, including Sofosbuvir, may lead to improved glucose metabolism and a reduction in blood sugar levels in diabetic patients.
- Close monitoring of blood glucose and adjustment of diabetes medication by a physician is necessary to prevent hypoglycemia.
- 7.
- **Hypersensitivity**: Patients with known allergies or sensitivities to Sofosbuvir or its inactive ingredients should inform their doctor before starting treatment.
- 8.
- **Alcohol Interaction**: The interaction between Sofosbuvir and alcohol is unknown; consultation with a doctor is advised before consumption.
- 9.
- **Other Liver Conditions**: Patients with liver problems other than chronic HCV should consult their doctors before taking Sofosbuvir.
How it Works (Mechanism of Action)
Sofosbuvir is a direct-acting antiviral agent (DAA) that inhibits the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase, which is essential for viral replication. It acts as a nucleotide analog prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203). This active metabolite is incorporated into the nascent HCV RNA by the NS5B polymerase, leading to chain termination and inhibition of viral replication.