Coronavir, 200 mg 50 pcs

Pharmacotherapeutic group: antiviral medicine

ATX code: J05AX27

Pharmacological properties

Pharmacodynamics

Antiviral activity in vitro

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 and 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 adamantan, 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.

The mechanism of action

Favipiravir is metabolized in cells to favipiravir ribosyltriphosphate (favipiravir RTF) and selectively inhibits the RNA-dependent RNA polymerase involved in influenza virus replication. Favipiravir RtF (1000 μmol/L) showed no inhibitory effect on human a DNA, but showed inhibitory effects ranging from 9.1% to 13.5% on β and from 11.7% to 41.2% on human γ 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 have been observed in clinical studies.

Pharmacokinetics

Intake

Favipiravir is easily absorbed in the gastrointestinal tract. Time to reach maximum concentration (Tmax) is 1.5 h.

Distribution

The binding to plasma proteins is about 54%.

Metabolism

Favipiravir is mainly metabolized by aldehydoxidase and partially metabolized to the hydroxylated form by xanthine oxidase. In cells the RTP of favipiravir is metabolized. Of the other metabolites, in addition to hydroxylate, glucuronate conjugate was also recorded in human plasma and urine.

Favipiravir is mainly excreted by the kidneys as the active metabolite hydroxylate, a small amount – unchanged. The elimination half-life (T1/2) is about 5 hours.

Patients with hepatic impairment

In favipiravirvir administration in patients with mild to moderate hepatic impairment (Child-Pugh grades A and B) the increase in Cmax and AUC was 1.5 and 1.8 times respectively compared to healthy volunteers. These increases in Cmax and AUC for patients with severe hepatic impairment (Child-Pugh class C) were 2.1 and 6.3-fold, respectively.

Patients with renal impairment

In patients with moderate renal impairment (GFR < 60 ml/min and ≥30 ml/min) the residual concentration of favipiravirvir (Ctrough) was increased 1.5-fold compared to patients without renal impairment. In patients with severe and terminal renal impairment (FFR < 30 ml/min) the drug has not been studied.

Indications

Active ingredient

Composition

One film-coated tablet contains:

The active substance: favipiravir – 200.0 mg.

Excipients: microcrystalline cellulose 101, colloidal silicon dioxide, povidone-K25, crosspovidone, sodium stearyl fumarate.

Film coating: Opadray II 85F220031 yellow [polyvinyl alcohol, titanium dioxide, macrogol 4000, talc, iron oxide yellow dye].

How to take, the dosage

The therapy regimen:

The drug should be taken orally, 30 minutes before meals.

For the treatment of new coronavirus infection caused by SARS-CoV-2 (COVID-19), the following dosing regimen is recommended:

The drug should be taken after laboratory confirmation of the diagnosis and/or if there is characteristic clinical symptomatology.

Interaction

The drug CORONAVIR is not metabolized by cytochrome P450, it is mainly metabolized by aldehydoxidase and partially metabolized by xanthine oxidase. The drug CORONAVIR inhibits aldehydoxidase and cytochrome CYP2C8, but does not induce cytochrome P450.

Table 2. Interdrug interactions

Special Instructions

If side effects develop, these should be reported for pharmacovigilance.

Before starting the drug CORONAVIR, the patient should be given written information about the effectiveness of the drug and the risks associated with its use (including the risk of effects on the embryo and fetus) and written consent should be obtained for the use of the drug.

Because animal studies of favipiravir have shown fetal death and teratogenicity, CORONAVIR should not be used in pregnant or presumptively pregnant women.

Synopsis

Contraindications

Hypersensitivity to favipiravir or any component of CORONAVIR.

Severe hepatic impairment (Child-Pugh class C).

Severe or terminal renal failure (GFR < 30 ml/min).

Pregnancy or pregnancy planning.

The period of breastfeeding.

Children under 18 years of age.

. In patients with a history of gout and hyperuricemia (elevated blood levels of uric acid and exacerbation of symptoms may occur), in elderly patients with mild to moderate hepatic impairment (Child-Pugh grades A and B), patients with moderate renal impairment (GFR < 60 ml/min and ≥30 ml/min).

Side effects

In the clinical trial of CORONAVIR, adverse reactions were observed in 29 of 37 patients (78.4%), including: hyperuricemia (in 23 patients (62.2%)), increased ALT (in 8 patients (21.6%)), increased ACT (in 6 patients (16.2%)), diarrhea (in 7 patients (18.9%)), increased creatine kinase (in 5 patients (13.5%)), hyperglycemia (in 4 patients (10.8%)), nausea (in 2 patients (5.4%)), epigastric pain (in 2 patients (5.4%)) increased LDH (in 1 patient (2.7%)), increased ferritin levels (in 1 patient (2.7%)), skin rash (in 2 patients (5.4%)), increased foot sweating (in 1 patient (2,7%)), foot chills (in 1 patient (2.7%)), headache (in 1 patient (2.7%)), weakness in the hand (in 1 patient (2.7%)), hematuria (in 1 patient (2.7%)).

The adverse reactions observed in clinical trials in patients with influenza infection (data from analyses in the pooled population pooled for safety assessment) are shown in Table 1.

The estimated incidence of adverse reactions is based on the WHO classification: Very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10,000, < 1/1000); very rare (< 1/10000); frequency unknown (frequency could not be established from available data).

Table 1. Adverse reactions

Pregnancy use

In preclinical studies of favipiravir at doses similar to or lower than clinical doses, early embryo death and teratogenicity were observed.

The drug CORONAVIR is contraindicated in pregnant women and in men and women during pregnancy planning. If the drug CORONAVIR is prescribed to women capable of childbearing (including those in postmenopause less than 2 years), it is necessary to confirm a negative result of a pregnancy test before starting treatment. A 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: for 1 month for women and for 3 months for men.

If CORONAVIR is prescribed to breastfeeding women it is necessary to stop breastfeeding while taking the drug and for 7 days after it ends because the main metabolite of favipiravir passes into the breast milk.

Similarities