Velpatasvir And Sofosbuvir

Brand Names: Epclusa

Drug Class: Hepatitis C Virus NS5A Inhibitor

Overview

11 DESCRIPTION Tablets EPCLUSA is a fixed-dose combination tablet containing sofosbuvir and velpatasvir for oral administration. Sofosbuvir is a nucleotide analog HCV NS5B polymerase inhibitor and velpatasvir is an NS5A inhibitor. Each 400 mg/100 mg tablet contains 400 mg sofosbuvir and 100 mg velpatasvir, and each 200 mg/50 mg tablet contains 200 mg sofosbuvir and 50 mg velpatasvir.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action EPCLUSA is a fixed-dose combination of sofosbuvir and velpatasvir, which are direct-acting antiviral agents against the hepatitis C virus [see Microbiology (12.4) ]. 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of sofosbuvir 400 mg (recommended dosage) and 1200 mg (3 times the recommended dosage) on QTc interval was evaluated in an active-controlled (moxifloxacin 400 mg) thorough QT trial. At a dose 3 times the recommended dose, sofosbuvir does not prolong QTc to any clinically relevant extent. The effect of velpatasvir 500 mg (5 times the recommended dosage) was evaluated in an active-controlled (moxifloxacin 400 mg) thorough QT trial.

Indications

  • 1 INDICATIONS AND USAGE EPCLUSA is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection [see Dosage and Administration (2.2 , 2.3 , 2.4) and Clinical Studies (14) ] : without cirrhosis or with compensated cirrhosis with decompensated cirrhosis for use in combination with ribavirin. EPCLUSA 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 adults...

Common Doses

  • 400 mg
  • 100 mg
  • 000 mg
  • 200 mg

Dosage

2 DOSAGE AND ADMINISTRATION Testing prior to the initiation of therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc. ( 2.1 ) See recommended treatment regimen and duration in patients 3 years of age and older with genotypes 1, 2, 3, 4, 5, or 6 HCV in table below: ( 2.2 ) Patient Population Regimen and Duration Treatment-naïve and treatment-experienced In clinical trials, regimens contained peginterferon alfa/ribavirin with or without an HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir).

Black Box Warning

WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death.

Contraindications

  • 4 CONTRAINDICATIONS EPCLUSA and ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin [see Dosage and Administration (2.2 , 2.3 , 2.4) ]. EPCLUSA and ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Serious Symptomatic Bradycardia When Coadministered with Amiodarone [see Warnings and Precautions (5.2) ]. The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed in adults and pediatric subjects 6 years of age and older with treatment with EPCLUSA for 12 weeks are headache and fatigue. ( 6.

Interactions

  • 7 DRUG INTERACTIONS P-gp inducers and/or moderate to strong CYP inducers (e.g., rifampin, St. John's wort, carbamazepine): May decrease concentrations of sofosbuvir and/or velpatasvir. Use of EPCLUSA with P-gp inducers and/or moderate to strong CYP inducers is not recommended. ( 5.3 , 7 ) Consult the full prescribing information prior to use for potential drug interactions. ( 5.2 , 5.3 , 7 ) Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications.