Comparative Pharmacology
Head-to-head clinical analysis: HARVONI versus INCIVEK.
Peer-Reviewed Evidence
Head-to-head clinical analysis: HARVONI versus INCIVEK.
HARVONI vs INCIVEK
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.
Inhibitor of the HCV NS3/4A serine protease, preventing cleavage of the HCV polyprotein, thereby inhibiting viral replication.
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.
Incivek (telaprevir) is administered orally at a dose of 750 mg (two 375 mg tablets) three times daily (every 7-9 hours) with food (not low-fat).
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 ranges from 4 to 13 hours (mean ~7 hours) in healthy volunteers; prolonged to 10-20 hours in HCV-infected patients.
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Approximately 91% of the radiolabeled dose is recovered in feces (79% as unchanged drug) and 9% in urine (1% as unchanged drug).
Category C
Category C
Antiviral
Antiviral