Comparative Pharmacology
Head-to-head clinical analysis: HARVONI versus ZOVIRAX.
Peer-Reviewed Evidence
Head-to-head clinical analysis: HARVONI versus ZOVIRAX.
HARVONI vs ZOVIRAX
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.
After intracellular phosphorylation to acyclovir triphosphate, selectively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.
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.
Herpes simplex: 200 mg orally 5 times daily for 10 days; or 400 mg orally 3 times daily for 5-10 days. Herpes zoster: 800 mg orally 5 times daily for 7-10 days. IV: 5-10 mg/kg every 8 hours for immunocompromised patients with HSV/VZV.
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 2.5-3.3 hours in adults with normal renal function; prolonged to 19.5 hours in anuria (creatinine clearance <10 mL/min).
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Renal excretion of unchanged drug via glomerular filtration and tubular secretion accounts for 76-82% of elimination; fecal excretion is less than 2%.
Category C
Category C
Antiviral
Antiviral