Ledipasvirsofosbuvir

Ledipasvirsofosbuvir is a fixed-dose combination antiviral medication used to treat chronic infection with the hepatitis C virus (HCV). It combines ledipasvir, an NS5A inhibitor, with sofosbuvir, a nucleotide analog NS5B polymerase inhibitor. The drug is typically formulated as a single tablet containing ledipasvir 90 mg and sofosbuvir 400 mg, marketed under the brand name Harvoni in many regions.

Indications and use

Ledipasvirsofosbuvir is indicated for the treatment of chronic HCV infection in adults and, in some countries, certain pediatric populations. It is effective across multiple HCV genotypes, most notably genotype 1, and may be used for other genotypes depending on regional approvals. Treatment duration is commonly 8 to 12 weeks, with the exact length depending on genotype, cirrhosis status, prior treatment history, and whether other therapies are used concurrently.

Mechanism of action

Ledipasvir inhibits NS5A, a viral protein essential for replication and assembly. Sofosbuvir inhibits the NS5B RNA polymerase, acting as a chain terminator to block viral RNA synthesis. The combination produces a potent, pangenotypic antiviral effect with a high barrier to resistance when used as directed.

Administration and safety

The tablet is taken orally once daily, with or without food. Caution is advised regarding drug interactions: P-glycoprotein and BCRP inducers can reduce drug levels; antacids and acid-reducing agents may affect absorption if not timed appropriately. Concomitant amiodarone can cause serious bradycardia in some patients. Common adverse effects include fatigue and headache; HBV reactivation has been reported in co-infected individuals who discontinue therapy. As with all HCV regimens, treatment should be individualized to the patient’s clinical status and genotype.