Description
Areplivir Pharmacodynamics
In vitro antiviral activity
Favipiravir has antiviral activity against laboratory strains of influenza A and B viruses (half maximum effective concentration (EC50) 0.014-0.55 µg/ml).
For influenza A and B virus strains resistant to adamantan (amantadine rimantadine), oseltamivir or zanamivir, the EC50 is 0.03-0.94 µg/mL and 0.09-0.83 µg/mL, respectively. For influenza A virus strains (including strains resistant to adamantan, oseltamivir, and zanamivir) such as swine influenza type A and avian influenza type A, including highly pathogenic strains (including H5N1 and H7N9), the EC50 is 0.06-3.53 µg/ml.
For influenza A and B virus strains resistant to adamantane, oseltamivir, and zanamivir, the EC50 is 0.09-0.47 µg/mL; no cross-resistance is observed.
Favipiravir inhibits the SARS-CoV-2 virus causing new coronavirus infection (COVID-19). The EC50 in Vero E6 cells is 61.88 μmol, corresponding to 9.72 μg/ml.
Mechanism of Action
Favipiravir is metabolized in cells to ribosyltriphosphate favipiravir (RTF favipiravir) and selectively inhibits the RNA-dependent RNA polymerase involved in influenza virus replication. Favipiravir RtF (1000 μmol/L) showed no inhibitory effect on human ? DNA, but showed inhibitory effects ranging from 9.1% to 13.5% on ? and ranging from 11.7% to 41.2% on human ? DNA. The inhibitory concentration (IC50) of favipiravir RTP for human RNA polymerase II was 905 μmol/L.
Resistance
After 30 transfections in the presence of favipiravir, no changes in the susceptibility of influenza A viruses to favipiravir were observed, and no resistant strains were observed either. No influenza viruses resistant to favipiravir were observed in the clinical studies conducted.
Indications
Treatment of new coronavirus infection (COVID-19).
Contraindications
Hypersensitivity to favipiravir or any component of AREPLIVIR.
Severe hepatic insufficiency (class C according to the Child-Pugh classification).
Severe or terminal renal failure (GFR <30 ml/min).
Pregnancy or pregnancy planning.
Breast-feeding period.
Childhood under 18 years of age.
Caution:
In patients with a history of gout and hyperuricemia (increased blood uric acid levels and exacerbation of symptoms are possible), in elderly patients, patients with mild to moderate hepatic impairment (Child-Pugh class A and B), patients with moderate renal impairment (GFR <60 ml/min and ?30 ml/min).
Use in pregnancy and during breastfeeding:
In preclinical studies of favipiravir at doses similar to or lower than clinical doses, early embryonic death and teratogenicity were observed. The drug AREPLIVIR is contraindicated in pregnant women, as well as in men and women during pregnancy planning. If AREPLIVIR is prescribed to women capable of childbearing (including postmenopausal women less than 2 years old), it is necessary to confirm a negative result of pregnancy test before the start of treatment. Repeated pregnancy test should be performed after the end of the drug. It is necessary to use effective methods of contraception (condom with spermicide) during and after taking the drug: within 1 month for women and within 3 months for men.
If AREPLIVIR is prescribed to breastfeeding women, breastfeeding should be stopped for the duration of drug administration and 7 days after its termination because the main metabolite of favipiravir reaches the breast milk.
Dosage and administration method
- Orally, 30 min before a meal.
- For treatment of new coronavirus infection (COVID-19) caused by SARS-CoV-2, the following dosing regimen is recommended:
- For patients with a body weight <75 kg, 1600 mg (8 tablets) 2 times on day 1 of therapy, then 600 mg (3 tablets) 2 times a day, respectively, from day 2 to day 10 of therapy;
- for patients with body weight of 75 kgs – 1800 mg (9 tablets) 2 times on the 1st day of therapy and further 800 mg (4 tablets) 2 times a day, respectively, from the 2nd to 10th day of therapy.
- The drug should be taken on the basis of the clinical picture and/or after laboratory confirmation of the diagnosis and in the presence of characteristic clinical symptoms.
- The total duration of treatment is 10 days or until confirmation of virus elimination, if earlier (two consecutive negative PCR test results at least 24 hours apart).
