HARVONI

What it is

HARVONI is a fixed-dose combination tablet containing 90 mg ledipasvir and 400 mg sofosbuvir . Ledipasvir is a hepatitis C virus (HCV) inhibitor targeting the HCV NS5A protein, which is essential for both RNA replication and the assembly of HCV virions . Sofosbuvir is a pangenotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication .

Approved indications —

Treatment of chronic hepatitis C (CHC) infection in adults

Dosing overview

The recommended dose of HARVONI tablets is one tablet, taken orally, once daily with or without food . Treatment duration and the addition of ribavirin vary according to HCV genotype, cirrhosis status, and treatment history. For genotype 1 patients without cirrhosis, HARVONI is given for 8 or 12 weeks; for those with cirrhosis, 12 weeks; for treatment-experienced patients with cirrhosis, HARVONI plus ribavirin is given for 12 or 24 weeks . For genotypes 4, 5 and 6, treatment-naïve patients without cirrhosis receive HARVONI for 12 weeks; those with cirrhosis receive 12 weeks; treatment-experienced patients without cirrhosis receive 12 weeks; and treatment-experienced patients with cirrhosis receive HARVONI plus ribavirin for 12 or 24 weeks .

Key safety warnings

Serious symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with a sofosbuvir-containing regimen, and a fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered ledipasvir/sofosbuvir . 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 HARVONI is not recommended . 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 HARVONI . Diabetics may experience dysglycaemia, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct-acting antiviral agents treatment, and glucose levels of diabetic patients initiating such therapy should be closely monitored, particularly within the first three months, and their diabetic medication modified when necessary . Drugs that are potent P-gp inducers such as rifampicin and St. John's Wort may significantly decrease ledipasvir and sofosbuvir plasma concentration leading to reduced therapeutic effect of HARVONI, and these agents should not be used with HARVONI .

Contraindications

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

PBS listing

HARVONI was recommended by PBAC in November 2014 for chronic hepatitis C virus (HCV) infection, genotype 1 . In November 2017, PBAC recommended an amendment to expand the eligibility criteria to include patients with chronic hepatitis C genotype 1, 3, 4, 5 or 6 who have compensated cirrhosis .

Regulatory history

HARVONI, a fixed-dose combination of ledipasvir and sofosbuvir, was approved by the TGA on 8 May 2015 . HARVONI (ledipasvir/sofosbuvir 90 mg/400 mg tablet) was first listed on the ARTG on 2015-05-13 . The PBAC recommended the listing of ledipasvir with sofosbuvir for chronic HCV genotype 1 in November 2014 on the basis of high clinical effectiveness and acceptable cost-effectiveness compared to existing treatments .