Ledipasvir-Sofosbuvir (Harvoni)

The fixed-dose combination of ledipasvir-sofosbuvir (Figure 1) and (Figure 2) provides an effective and well-tolerated one-pill once-a-day option for treatment of genotypes 1, 4, 5, and 6 chronic hepatitis C (HCV) infection. This direct-acting antiviral regimen was the first FDA-approved interferon- and ribavirin free regimen to treat hepatitis C. Ledipasvir-sofosbuvir can be used without ribavirin in most patients with genotype 1A, except those who are cirrhotic and treatment-experienced. In addition, persons with HCV genotype 1 may be eligible for an 8-week duration if they are treatment-naïve, without cirrhosis, and have a pretreatment HCV RNA level less than 6 million. Similar to sofosbuvir-velpatasvir, the other NS5B-NS5A inhibitor combination, ledipasvir-sofosbuvir has been shown to be safe and effective for the treatment of HCV in persons with decompensated cirrhosis.

Available data from clinical trials has demonstrated the combination of ledipasvir-sofosbuvir has been very well tolerated. The most common reported adverse effects are fatigue and headache.

Ledipasvir is a potent inhibitor of HCV NS5A, a viral phosphoprotein that plays an important role in viral replication, assembly, and secretion. Sofosbuvir is a nucleotide analog inhibitor of hepatitis C virus NS5B polymerase—the key enzyme mediating HCV RNA replication. The triphosphate form of sofosbuvir (GS-461203) mimics the natural cellular uridine nucleotide and is incorporated by the HCV RNA polymerase into the elongating RNA primer strand, resulting in viral chain termination.

The fixed dose combination ledipasvir-sofosbuvir (90 mg/400 mg) is indicated for treatment, with or without ribavirin, for the treatment of patients with chronic hepatitis C genotypes 1, 4, 5, and 6. The detailed indications are listed below. When treating patients coinfected with HCV and HIV, the recommendations are the same as listed below. 

Genotype 1

• Treatment-naïve patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) : ledipasvir-sofosbuvir x 12 weeks*
• Treatment-experienced** patients without cirrhosis: ledipasvir-sofosbuvir x 12 weeks
• Treatment-experienced** patients with compensated cirrhosis (Child-Pugh A): ledipasvir-sofosbuvir x 24 weeks^†
• Treatment-naïve and treatment-experienced** patients with decompensated cirrhosis (Child-Pugh B or C): ledipasvir-sofosbuvir plus ribavirin^‡ x 12 weeks

Genotype 1 or 4

• Treatment-naïve and treatment-experienced ** liver transplant recipients without cirrhosis, or with compensated cirrhosis (Child-Pugh A): ledipasvir-sofosbuvir plus ribavirin^§ x 12 weeks

Genotype 4, 5, or 6

• Treatment-naïve and treatment-experienced ** patients without cirrhosis or with compensated cirrhosis (Child-Pugh A): ledipasvir-sofosbuvir plus ribavirin x 12 weeks

Footnotes
*Based on a subset analysis from the ION-3 trial, ledipasvir-sofosbuvir for 8 weeks can be considered in treatment-naïve genotype 1 patients without cirrhosis who have pre‑treatment HCV RNA less than 6 million IU/mL.

**Treatment-experienced patients include those who have failed a peginterferon alfa plus ribavirin based regimen, with or without an HCV protease inhibitor.

^†Ledipasvir-sofosbuvir for 12 weeks can be considered in treatment-experienced genotype 1 patients with cirrhosis who are eligible for ribavirin (see footnote^§ for ribavirin dosage recommendations).

^‡In patients with decompensated cirrhosis, the starting dosage of ribavirin is 600 mg and can be titrated up to 1000 mg for patients <75 kg and 1200 mg for those ≥75 kg in two divided doses with food. If the starting dosage of ribavirin is not well tolerated, the dosage should be reduced as clinically indicated based on hemoglobin levels.

^§For patients without cirrhosis or with compensated cirrhosis (Child-Pugh A), the daily dosage of ribavirin is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in two divided doses with food.

Ledipasvir-sofosbuvir (90 mg/400 mg) is a fixed-dose combination tablet. The recommended dosage is one tablet once daily, with or without food.

• For patients with any degree of renal impairment including end-stage renal disease requiring dialysis, no dosage adjustment is necessary.
• For patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C), no dosage adjustment is recommended, but the safety and efficacy of ledipasvir-sofosbuvir in patients with decompensated cirrhosis has not been established.

Gilead Sciences has an active ledipasvir-sofosbuvir (Harvoni) patient assistance program for eligible patients with hepatitis C who do not have insurance and are not covered by Medicaid or Medicare. Information regarding the Gilead Sciences ledipasvir-sofosbuvir patient assistance program can be obtained at the Support Path website or by calling 1-855-769-7284.

Ledipasvir-sofosbuvir (Harvoni) Full Prescribing Information.