Not only does favipiravir inhibit replication of influenza A and B, but the drug has shown promise in the treatment of avian influenza, and may be an alternative option for influenza strains that are resistant to neuramidase inhibitors. Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19.
Indications: Treatment of Novel Viruses including Ebola and COVID-19. Influenza unresponsive to conventional treatment.
Dosage: The recommended oral dosing regimen for favipiravir is as follows: Day 1: 1600 mg twice daily; Days 2-5: 600 mg twice daily.
Pharmacodynamics: Favipiravir functions as a prodrug and undergoes ribosylation and phosphorylation intracellularly to become the active favipiravir-RTP. Favipiravir-RTP binds to and inhibits RNA dependent RNA polymerase (RdRp), which ultimately prevents viral transcription and replication.
Mechanism of action: The mechanism of action of favipiravir is novel compared to existing influenza antivirals that primarily prevent entry and exit of the virus from cells. The active favipiravir-RTP selectively inhibits RNA polymerase and prevents replication of the viral genome. There are several hyptheses as to how favipiravir-RTP interacts with RNA dependent RNA polymerase (RdRp). When favipiravir-RTP is incorporated into a nascent RNA strand, it prevents RNA strand elongation and viral proliferation. Studies have also found that the presence of puring analogs can reduce favipiravir's antiviral activity, suggesting competition between favipiravir-RTP and puring nucleosides for RdRp binding.
Absorption: The bioavailability of favipiravir is almost complete at 97.6%. The mean Cmax for the recommended dosing schedule of favipiravir is 51.5 ug/mL. Studies comparing the pharmacokinetic effects of multiple doses of favipiravir in healthy American and Japanese subjects are below: Japanese subjects First Dose: Cmax = 36.24 ug/mL tmax = 0.5 hr AUC = 91.40 ugxhr/mL American subjects First Dose: Cmax = 22.01 ug/mL tmax = 0.5 hr AUC = 44.11 ugxhr/mL Japanese Subjects Final Dose: Cmax = 36.23 ug/mL Tmax = 0.5 hr AUC = 215.05 ugxhr/mL American Subjects Final Dose: Cmax = 23.94 ug/mL Tmax = 0.6 hr AUC = 73.27 ugxhr/mL When favipiravir was given as a single dose of 400 mg with food, the Cmax decreased. It appears that when favipiravir is given at a higher dose or in multiple doses, irreversible inhibition of aldehyde oxidase (AO) occurs and the effect of food on the Cmax is lessened.
Route of Elimination: Favipiravir's metabolites are predominantly renally cleaered.
Volume of Distribution: The apparent volume of distribution of favipiravir is 15 - 20 L.
Clearance: The recommended oral dosing regimen for favipiravir is as follows: Day 1: 1600 mg twice daily; Days 2-5: 600 mg twice daily. The reported CL/F for favipiravir 1600 mg dosed once daily is 2.98 L/hr ±0.30 and the CL/F values for favipiravir 600 mg dosed twice daily on days 1-2 and once daily on days 3-7 were 6.72 L/hr ±1.68 on Day 1, and 2.89 L/hr ±0.91 on Day 7. There is currently no reported clearance data for favipiravir 1600 mg dosed twice daily.
Metabolism: Favipiravir is extensively metabolised with metabolites excreted mainly in the uring. The antiviral undergoes hydroxylation primarily by aldehyde oxidase and to a lesser extent by xanthine oxidase to the inactive metabolite.
Half-life: The elimination half-life of favipiravir is estimated to range from 2 to 5.5 hours.