Comparative Pharmacology
Head-to-head clinical analysis: HARVONI versus VALACYCLOVIR HYDROCHLORIDE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: HARVONI versus VALACYCLOVIR HYDROCHLORIDE.
HARVONI vs VALACYCLOVIR HYDROCHLORIDE
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.
Valacyclovir hydrochloride is a prodrug of acyclovir. After oral administration, it is rapidly converted to acyclovir, which inhibits viral DNA polymerase, leading to chain termination and inhibition of viral DNA 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.
500 mg orally twice daily for recurrent genital herpes; 1 g orally twice daily for herpes zoster; 1 g orally three times daily for herpes simplex encephalitis or immunocompromised patients.
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: 2.5–3.3 hours in patients with normal renal function; prolonged to 14 hours in renal impairment (CrCl 15–30 mL/min).
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Renal excretion: >90% as unchanged drug and inactive metabolite (9-carboxymethoxymethylguanine). Biliary/fecal: <2%.
Category C
Category A/B
Antiviral
Antiviral