Fixvel
Generic Name:Sofosbuvir 400mg + Velpatasvir 100 mg
Indications
This is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor and velpatasvir, an HCV NS5A inhibitor and is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection:
- without cirrhosis or with compensated cirrhosis
- with decompensated cirrhosis for use in combination with ribavirin
Pharmacology
Mechanism of Action: Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a with an IC50 value ranging from 0.36 to 3.3 micromolar. GS-461203 is neither an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase. Velpatasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication. Resistance selection in cell culture and cross-resistance studies indicate Velpatasvir targets NS5A as its mode of action.
Pharmacodynamics: Cardiac Electrophysiology: The effect of Sofosbuvir 400 mg (recommended dosage) and 1200 mg (three times the recommended dosage) on QTc interval was evaluated in an active-controlled (Moxifloxacin 400 mg) thorough QT trial. At a dose three times the recommended dose, Sofosbuvir does not prolong QTc to any clinically relevant extent. The effect of Velpatasvir 500 mg (five times the recommended dosage) was evaluated in an active-controlled (Moxifloxacin 400 mg) thorough QT trial. At a dose five times the recommended dose, Velpatasvir does not prolong QTc interval to any clinically relevant extent.
Dosage & Administration
Testing prior to the initiation of therapy: Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with Sofosbuvir & Velpatasvir.
Recommended Treatment Regimen and Duration in Patients 3 Years of Age and Older: Below table shows the recommended treatment regimen and duration based on patient population. For patients with HCV/HIV-1 coinfection, follow the dosage recommendations in table below. For treatment-naïve and treatment-experienced liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A), the recommended regimen is Sofosbuvir & Velpatasvir once daily for 12 weeks.
Recommended Treatment Regimen and Duration in Patients 3 Years of Age and Older with Genotype 1, 2, 3, 4, 5 or 6 HCV.
Recommended Dosage in Adults: The recommended dosage of Sofosbuvir & Velpatasvir in adults is one tablet (400 mg sofosbuvir and 100 mg velpatasvir) taken orally once daily with or without food. When administered with Sofosbuvir & Velpatasvir, the recommended dosage of ribavirin is based on weight (administered with food): 1,000 mg per day for patients less than 75 kg and 1,200 mg for those weighing at least 75 kg, divided and administered twice daily. The starting dosage and on-treatment dosage of ribavirin can be decreased based on hemoglobin and creatinine clearance. For ribavirin dosage modifications refer to the ribavirin prescribing information.
Recommended Dosage in Pediatric Patients 3 Years of Age and Older: The recommended dosage of Sofosbuvir & Velpatasvir in pediatric patients 3 years of age and older is based on weight and provided in table below
Dosing for Pediatric Patients 3 Years and Older with Genotype 1, 2, 3, 4, 5 or 6 HCV Using Sofosbuvir & Velpatasvir tablets.
