Comparative Pharmacology
Head-to-head clinical analysis: CIDOFOVIR versus HARVONI.
Peer-Reviewed Evidence
Head-to-head clinical analysis: CIDOFOVIR versus HARVONI.
CIDOFOVIR vs HARVONI
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Cidofovir is a nucleotide analog that inhibits viral DNA polymerase by competing with deoxycytidine triphosphate for incorporation into viral DNA, resulting in chain termination and inhibition of viral replication.
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.
5 mg/kg intravenously once weekly for 2 weeks, then 5 mg/kg every 2 weeks. Administer with probenecid 2 g orally 3 hours before dose, then 1 g at 2 and 8 hours after dose. Hydrate with 1 L normal saline before infusion.
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.
None Documented
None Documented
Clinical Note
moderateCidofovir + Teriflunomide
"The serum concentration of Teriflunomide can be increased when it is combined with Cidofovir."
Clinical Note
moderateTenofovir disoproxil + Cidofovir
"Tenofovir disoproxil may decrease the excretion rate of Cidofovir which could result in a higher serum level."
Terminal elimination half-life is approximately 2.5 hours. However, the intracellular half-life of the active diphosphate metabolite is >48 hours, supporting once-weekly dosing.
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
Renal excretion of unchanged drug via glomerular filtration and tubular secretion accounts for approximately 90% of the administered dose. Biliary/fecal elimination is minimal (<5%).
Ledipasvir: 86% fecal, 1% renal; Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; GS-331007: 78% renal
Category D/X
Category C
Antiviral
Antiviral