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

Treatment of new coronavirus infection (COVID-19).

Pharmacological effect

Pharmacotherapeutic group: antiviral agent

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 strains of influenza A and B viruses resistant to adamantane (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 adamantane, 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 strains of influenza A and B viruses resistant to adamantane, oseltamivir and zanamivir, EC50 is 0.09-0.47 μg/ml; cross-resistance is not observed.

Favipiravir inhibits the SARS-CoV-2 virus, which causes novel coronavirus disease (COVID-19). The EC50 in Vero E6 cells is 61.88 µmol, which corresponds to 9.72 µg/ml.

Mechanism of action

Favipiravir is metabolized in cells to favipiravir ribosyltriphosphate (favipiravir RTP) and selectively inhibits RNA-dependent RNA polymerase involved in influenza virus replication. Favipiravir RTF (1000 μmol/L) showed no inhibitory effect on human α DNA, but showed an inhibitory effect ranging from 9.1 to 13.5% on β and ranging from 11.7 to 41.2% on human γ DNA. The inhibitory concentration (IC50) of favipiravir PTF for human RNA polymerase II was 905 μmol/L.

Resistance

After 30 subcultures in the presence of favipiravir, no changes were observed in the susceptibility of influenza A viruses to favipiravir, and no resistant strains were observed. Clinical studies have not revealed the emergence of influenza viruses resistant to favipiravir.

Pharmacokinetics

Suction

Favipiravir is easily absorbed from the gastrointestinal tract. Time to reach maximum concentration (Tmax) – 1.5 hours.

Distribution

Plasma protein binding is about 54%.

Metabolism

Favipiravir is primarily metabolized by aldehyde oxidase and partially metabolized to its hydroxylated form by xanthine oxidase. Favipiravir RTF is metabolized in cells. Of the other metabolites, in addition to hydroxylate, glucuronate conjugate was also recorded in human blood plasma and urine.

Removal

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

Patients with liver dysfunction

When favipiravir was taken by patients with mild to moderate hepatic impairment (Child-Pugh classes 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 times, respectively.

Patients with impaired renal function

In patients with moderate renal impairment (GFR <60 ml/min and ≥30 ml/min), the residual concentration of favipiravir (Ctrough) increased by 1.5 times compared with patients without renal impairment. The drug has not been studied in patients with severe and terminal renal failure (GFR < 30 ml/min).

Special instructions

If a side effect develops, it is necessary to report this in the prescribed manner for the implementation of pharmacovigilance measures.

Before starting to take the drug CORONAVIR, the patient must provide 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 obtain written consent to use the drug.

Because fetal death and teratogenicity were observed in animal studies of favipiravir, CORONAVIR should not be administered to pregnant or suspected pregnant women.

When prescribing CORONAVIR to women capable of childbearing (including those less than 2 years postmenopausal), it is necessary to confirm a negative pregnancy test result before starting treatment. Women of childbearing potential should be fully explained the risks and carefully instructed to use the most effective method of contraception with their partners while taking the drug and for 1 month afterwards (condom with spermicide). If you suspect a possible pregnancy, you should immediately stop taking the drug and consult your doctor.
When distributed in the human body, the drug CORONAVIR enters the semen. When prescribing the drug, male patients must be fully explained the risks and carefully instructed to use the most effective methods of contraception during sexual intercourse while taking the drug and for 3 months after its end (condom with spermicide). Additionally, male patients should be instructed not to have sexual contact with pregnant women.
When distributed in the human body, the drug CORONAVIR passes into breast milk. When prescribing the drug, breastfeeding women should be fully explained the risks and carefully instructed to stop breastfeeding while taking the drug and for 7 days after it ends.
Impact on the ability to drive vehicles and machinery

Active ingredient

Favipiravir

Composition

One film-coated tablet contains:

Active ingredient: favipiravir – 200.0 mg.

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

Film shell: Opadry II 85F220031 yellow [polyvinyl alcohol, titanium dioxide, macrogol 4000, talc, iron oxide yellow].

Pregnancy

Early embryonic lethality and teratogenicity were observed in preclinical studies of favipiravir at doses similar to or lower than clinical doses.

The drug CORONAVIR is contraindicated in pregnant women, as well as in men and women planning pregnancy. When prescribing CORONAVIR to women capable of childbearing (including those less than 2 years postmenopausal), it is necessary to confirm a negative pregnancy test result before starting treatment. A repeat pregnancy test must be performed after stopping the drug. It is necessary to use effective methods of contraception (condom with spermicide) while taking the drug and after its completion: for 1 month for women and for 3 months for men.

When prescribing CORONAVIR, nursing women must stop breastfeeding while taking the drug and for 7 days after finishing it, since the main metabolite of favipiravir passes into breast milk.

Contraindications

Hypersensitivity to favipiravir or any component of the drug CORONAVIR.

Severe liver failure (class C according to the Child-Pugh classification).

Renal failure of severe and terminal severity (GFR < 30 ml/min).

Pregnancy or planning pregnancy.

Breastfeeding period.

Children under 18 years of age.

With caution

In patients with gout and a history of hyperuricemia (possible increased levels of uric acid in the blood and exacerbation of symptoms), in elderly patients with mild to moderate liver failure (Child-Pugh classes A and B), patients with moderate renal failure (GFR <60 ml/min and ≥30 ml/min).

Side Effects

In a clinical trial of the drug CORONAVIR, adverse reactions were observed in 29 patients out of 37 (78.4%), including: hyperuricemia (in 23 patients (62.2%)), increased ALT (in 8 patients (21.6%)), increased AST (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 sweating of the feet (in 1 patient (2.7%)), chilly feet (in 1 patient (2.7%)), headache (in 1 patient (2.7%)), weakness in the arm (in 1 patient (2.7%)), hematuria (in 1 patient (2.7%)).

Adverse reactions observed in clinical trials in patients with influenza infection (analyzed in the pooled safety population) are presented in Table 1.

The assessment of the incidence of adverse reactions is based on the WHO classification: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (< 1/10000); frequency is unknown (it is not possible to establish the frequency from the available data).

Table 1. Adverse reactions

Classification by organ systems
Adverse reactions
Blood and lymphatic system disorders
Common: neutropenia, leukopenia
Rare: leukocytosis, monocytosis, reticulocytopenia
Metabolic and nutritional disorders
Common: hyperuricemia, hypertriglyceridemia
Uncommon: glycosuria
Rare: hypokalemia
Immune system disorders
Uncommon: rash
Rare: eczema, itching
Respiratory, thoracic and mediastinal disorders
Rarely: bronchial asthma, sore throat, rhinitis, nasopharyngitis
Gastrointestinal disorders
Common: diarrhea
Uncommon: nausea, vomiting, abdominal pain
Rare: abdominal discomfort, duodenal ulcer, bloody stools, gastritis
Liver disorders
Often: increased ALT activity, increased AST activity, increased glutamyltransferase (GGT) and biliary tract activity
Rarely: increased alkaline phosphatase (ALP) activity, increased bilirubin concentration in the blood
Other
Rare: abnormal behavior, increased creatine phosphokinase (CPK) activity, hematuria, laryngeal polyp, hyperpigmentation, taste disturbance, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain

Interaction

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

Table 2. Drug-drug interactions

Preparation
Signs, symptoms and treatment
Mechanism and risk factors
Pyrazinamide
Hyperuricemia
Additionally, reabsorption of uric acid in the renal tubules increases
Repaglinide
The concentration of repaglinide in the blood may increase, and adverse reactions to repaglinide may develop.
Inhibition of CYP2C8 leads to increased blood concentrations of repaglinide
Theophylline
The concentration of favipiravir in the blood may increase, and adverse reactions to favipiravir may develop
Interaction with xanthine oxidase may lead to increased blood concentrations of favipiravir
Famciclovir, sulindac
The effectiveness of these drugs may be reduced
Inhibition of aldehyde oxidase by favipiravir may lead to a decrease in the concentration of active forms of these drugs in the blood

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

1 year Do not use after expiration date.

Manufacturer

R-Pharm JSC, Russia