EPCLUSA

What it is

EPCLUSA is a fixed-dose combination tablet containing sofosbuvir 400 mg and velpatasvir 100 mg. The active substances in EPCLUSA tablets are sofosbuvir and velpatasvir. Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication and undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate that acts as a chain terminator. Velpatasvir is a HCV inhibitor targeting the HCV NS5A protein, which is essential for both RNA replication and the assembly of HCV virions.

Approved indications —

Chronic hepatitis C virus (HCV) infection (genotype 1, 2, 3, 4, 5 or 6) in adults and paediatric patients ≥ 12 years of age and weighing ≥ 30 kg.

Dosing overview

The recommended dose of EPCLUSA in adults is one tablet, taken orally, once daily with or without food. For patients without cirrhosis and patients with compensated cirrhosis, EPCLUSA is taken for 12 weeks. For patients with decompensated cirrhosis, EPCLUSA is combined with ribavirin for 12 weeks, with a ribavirin starting dose of 600 mg daily and dose adjustment according to tolerance. In paediatric patients ≥ 12 years of age and weighing ≥ 30 kg, the recommended dosage is one tablet taken orally once daily with or without food for 12 weeks.

Key safety warnings

Serious symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir-containing regimens. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen. Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Coadministration of amiodarone with EPCLUSA is not recommended. For patients taking amiodarone who have no other alternative viable treatment options, cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Cases of hepatitis B virus (HBV) reactivation, including fatal cases, have been reported during and after treatment of HCV with direct-acting antiviral agents in HCV/HBV co-infected patients. Screening for current or past HBV infection, including testing for HBV surface antigen (HBsAg) and HBV core antibody (anti-HBc), should be performed in all patients before initiation of treatment with EPCLUSA. Diabetics may experience dysglycaemia, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct-acting antiviral treatment. Glucose levels of diabetic patients initiating direct-acting antiviral therapy should be closely monitored, particularly within the first three months, and their diabetic medication modified when necessary.

Contraindications

EPCLUSA tablets are contraindicated in patients with known hypersensitivity to the active substance or to any other component of the tablets. EPCLUSA should not be administered concurrently with other medicinal products containing any of the same active components.

PBS listing

EPCLUSA was recommended by PBAC in November 2016 for chronic HCV infection (genotypes 1–6, with or without cirrhosis; with ribavirin for decompensated liver disease) with Authority Required General Schedule and Section 100 listing.

Regulatory history

EPCLUSA (sofosbuvir 400 mg / velpatasvir 100 mg tablet) was first listed on the ARTG on 19 December 2016. In November 2016, PBAC recommended EPCLUSA for chronic HCV infection (genotypes 1–6, with or without cirrhosis; with ribavirin for decompensated liver disease) with Authority Required General Schedule and Section 100 listing and a Risk Sharing Arrangement. In November 2017, PBAC recommended an amendment to the PBS listing to expand the eligibility criteria for sofosbuvir and velpatasvir to include patients with chronic hepatitis C of any genotype who have compensated cirrhosis. The AusPAR was published on 9 April 2021.