Comparative Pharmacology
Head-to-head clinical analysis: HARVONI versus SYMADINE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: HARVONI versus SYMADINE.
HARVONI vs SYMADINE
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.
SYMADINE (amantadine) is a tricyclic amine that inhibits influenza A virus replication by blocking the viral M2 ion channel, which prevents uncoating of viral RNA. It also increases dopamine release and inhibits dopamine reuptake in the CNS, providing antiparkinsonian effects.
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.
100 mg orally every 12 hours; immediate-release formulation.
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
The terminal elimination half-life is approximately 24 hours in patients with normal renal function. In patients with renal impairment (CrCl <50 mL/min), the half-life is significantly prolonged, requiring dose adjustment. The long half-life allows for once-daily dosing.
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Renal elimination of unchanged drug accounts for approximately 90% of the administered dose. Biliary/fecal excretion is minimal (<5%).
Category C
Category C
Antiviral
Antiviral and Antiparkinsonian