Comparative Pharmacology
Head-to-head clinical analysis: HARVONI versus HEPSERA.
Peer-Reviewed Evidence
Head-to-head clinical analysis: HARVONI versus HEPSERA.
HARVONI vs HEPSERA
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Fixed-dose combination of ledipasvir, an HCV NS5A inhibitor, and sofosbuvir, an HCV NS5B nucleotide polymerase inhibitor. Ledipasvir inhibits HCV NS5A protein essential for viral replication and assembly; sofosbuvir is a prodrug that after intracellular metabolism acts as a chain terminator by inhibiting NS5B RNA-dependent RNA polymerase.
Acyclic nucleotide analog of adenosine monophosphate; inhibits hepatitis B virus (HBV) DNA polymerase by competing with the natural substrate dATP, causing DNA chain termination after incorporation into viral DNA.
One tablet (90 mg ledipasvir/400 mg sofosbuvir) orally once daily with or without food for 12 weeks. For treatment-naïve patients with genotype 1 and cirrhosis, 24 weeks may be considered. For genotype 4, 12 weeks recommended.
10 mg orally once daily.
None Documented
None Documented
Ledipasvir: 47 hours; Sofosbuvir: 0.5 hours; GS-331007 (predominant circulating metabolite): 27 hours; clinical context: supports once-daily dosing with no accumulation beyond steady state by day 7
Terminal elimination half-life is approximately 6-9 hours in patients with normal renal function. In renal impairment, half-life is prolonged (up to 18 hours in moderate impairment, >30 hours in severe impairment). Steady-state is achieved within 5-7 days.
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Primarily renal; 70-90% of an oral dose is excreted unchanged in urine via active tubular secretion and glomerular filtration. Biliary/fecal elimination accounts for <5%.
Category C
Category C
Antiviral
Antiviral