Coronavir (Favipiravir) 200mg 50 pills

One film-coated tablet contains:

Active substance: favipiravir - 200.0 mg.

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

Cap: Opadray II 85F220031 yellow [polyvinyl alcohol, titanium dioxide, macrogol 4000, talcum, iron oxide yellow dye].

Pharmacotherapy 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 (EU50) 0.014-0.55 μg/ml).

For strains of influenza A and B viruses resistant to adamantan (amantadine and rimantadine), oseltamivir or zanamivir, ES50 is 0.03-0.94 μg/ml and 0.09-0.83 μg/ml, respectively. For strains of influenza A virus (including strains resistant to Adamanthan, oseltamivir and zanamivir), such as swine influenza type A and avian influenza type A, including highly pathogenic strains (including H5N1 and H7N9), EC50 is 0.06-3.53 μg/ml.

For strains of influenza A and B viruses resistant to adamanthan, oseltamivir and zanamivir, ES50 is 0.09-0.47 μg/ml; cross resistance is not observed.

Favipiravir inhibits the SARS-CoV-2 virus, which causes a new coronavirus infection (COVID-19). ES50 in Vero E6 cells is 61.88 μmol, which corresponds to 9.72 μg/ml.

Mechanism of action

Favipiravir is metabolized in cells before favipiravir ribosyl triphosphate (Favipiravir) and selectively inhibits RNA-dependent RNA polymerase involved in influenza virus replication. Favipiravir RTF (1000 μmol/l) did not show an inhibitory effect on human DNA, but showed an inhibitory effect in the range from 9.1 to 13.5% per β and in the range from 11.7 to 41.2% on human DNA γ. The inhibitory concentration (IC50) of Favipiravir RTF for human RNA II polymerase was 905 μmol/l.

Resistance

After 30 transplants in the presence of favipiravir ns, there were changes in the susceptibility of influenza viruses type A to favipiravir, no resistant strains were also observed. No appearance of influenza viruses resistant to favipiravir was found in clinical studies.

Pharmacokinetics

Suction

Favipiravir is easily absorbed in the gastrointestinal tract. The time to reach the maximum concentration (Tmax) is 1.5 hours.

Distribution

Plasma protein binding is about 54%.

Metabolism

Favipiravir is mainly metabolized by aldehyde oxidase and partially metabolized to hydroxylated form by xanthin oxidase. Favipiravir RTF is metabolized in cells. Of other metabolites, in addition to hydroxylate, glucuronate conjugate was also registered in human plasma and urine.

Withdignment

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

Patients with liver disfunction

When taking favipiravir by patients with mild to moderate liver failure (classes A and B according to the Child Pugh classification), the increase in Cmax and AUC was 1.5 and 1.8 times, respectively, compared to healthy volunteers. Data on Cmax and AUC increases for patients with severe liver failure (Child Pugh Class C) were 2.1 and 6.3 times, respectively.

Patients with kidney dysfunction

In patients with moderate renal failure (SCF <60 ml/min and ≥30 ml/min), the residual concentration of Favipiravir (Ctrough) increased 1.5 times compared to patients without kidney dysfunction. In patients with severe and terminal severity renal failure (SCF <30 ml/min), the drug was not studied.

Treatment of a new coronavirus infection (COVID-19).

In preclinical studies of favipiravir in dosages similar to clinical or lower, there was an early death of the embryo and teratogenicity.

CORONAVIR is contraindicated for pregnant women, as well as men and women during pregnancy planning. When prescribing CORONAVIR to women capable of childbirth (including in postmenopausal less than 2 years), it is necessary to confirm the negative result of the pregnancy test before treatment begins. A second pregnancy test must be carried out after the end of taking the drug. Effective methods of contraception (condom with spermicide) should be used during and after taking the drug: for 1 month for women and for 3 months for men.

When prescribing CORONAVIR to lactating women, it is necessary to stop breastfeeding during taking the drug and within 7 days after its end, as the main metabolite of favipiravir enters breast milk.

Hypersensitivity to favipiravir or any component of CORONAVIR.

Severe liver failure (Child Pugh Class C).

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

Pregnancy or pregnancy planning.

Breastfeeding period.

Children under 18 years of age.

With caution

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

In a clinical study of CORONAVIR, undesirable 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 ACT (in 6 patients (16.2%)), diarrhea (7 patients (18.9%)), increased creatine kinase (in 5 patients (13.5%)), hyperglycemia (in 4 patients (10.8%)), nausea (in 2 patients (5.4%)), pain in the epigastrics (in 2 patients (5.4%)), increased LDH (in 1 patient (2.7%)), skin rash (in 1 patient (2.4%)), skin rash (in 2 patients (5.7%)), increased foot sweating (in 1 patient (7%) foot chilliness (1 patient (2.7%)), headache (1 patient (2.7%)), hand weakness (1 patient (2.7%)), hematuria (1 patient (2.7%)).

Undesirable reactions observed in clinical trials in patients with influenza infection (analysis data in the total population united for safety assessment) are presented in Table 1.

The estimate of the frequency of adverse adverse reactions is based on the WHO classification: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); rarely (≥1/10 000, <1/1000); very rarely (<1/10000); frequency is unknown (it is not possible to

Table 1. Unwanted reactions

Classification by organ system	Unwanted reactions
Blood and lymphatic system disorders	Often: neutropenia, leukopenia Rarely: leukocytosis, monocytosis, reticulocytopenia
Metabolic and nutritional disorders	Often: hyperuricemia, hypertriglyceridemia Infrequently: glucosuria Rarely: hypokalemia
Immune system disorders	Infrequently: rash Rarely: eczema, itching
Disorders from the respiratory system, chest and mediastinum	Rarely: bronchial asthma, sore throat, rhinitis, nasopharyngitis
Gastrointestinal disorders	Often: diarrhea Infrequently: nausea, vomiting, abdominal pain Rarely: abdominal discomfort, duodenal ulcer, bloody chair, gastritis
Liver disorders	Often: increased ALT activity, increased ACT activity, increased glutamyltransferase (GGT) and biliary tract activity Rarely: increased activity of alkaline phosphatase (PF), increased concentration of bilirubin in the blood
Others	Rarely: abnormal behavior, increased creatine phosphokinase (CFC), hematuria, larynx polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, ventricular extrasystoles, chest pain

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

Table 2. Interdrug interactions

The drug	Signs, symptoms and treatment	Mechanism and risk factors
Pyrazinamide	Hyperuricemia	Additionally, reabsorption of uric acid in renal tubules increases
Repaglinide	The concentration of repaglinide in the blood may increase, unwanted reactions to repaglinide may develop	Inhibition of CYP2C8 leads to an increase in the concentration of repaglinide in the blood
Theophylline	The concentration of favipiravir in the blood may increase, unwanted reactions to favipiravir may develop	Interaction with xanthinoxidase can lead to an increase in the concentration of favipiravir in the blood
Famcyclovir, sulindak	The effectiveness of these drugs may be reduced	Inhibition of aldehyde oxidase with favipiravir can lead to a decrease in the concentration of active forms of these drugs in the blood

Therapy scheme:

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

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

• for patients with body weight <75 kg: 1600 mg (8 tablets) 2 times a day on the 1st day of therapy, then 600 mg (3 tablets) 2 times a day from the 2nd to the 10th day of therapy, respectively; 70 tablets are required for the course
• for patients with body weight ≥75 kg: 1800 mg (9 tablets) 2 times a day on the 1st day of therapy, then 800 mg (4 tablets) 2 times a day from the 2nd to the 10th day of therapy, respectively; 90 tablets are required for the course.

The drug should be taken after laboratory confirmation of the diagnosis and/or in the presence of characteristic clinical symptoms.

The tablets are round, biconvex, coated with a light yellow film shell with a brownish tint of color. At the cross-section, the tablet core is from white to light yellow.

In case of side effects, it is necessary to report this in accordance with the established procedure for the implementation of pharmacovigilance activities.

Before taking the drug CORONAVIR, the patient must provide written information on the effectiveness of the drug and the risks associated with its use (including the risk of affecting the embryo and fetus), and obtain written consent to the use of the drug.

Since animal favipiravir studies observed embryo death and teratogenicity, CORONAVIR should not be prescribed to pregnant and presumably pregnant women.

1. When prescribing CORONAVIR to women capable of childbirth (including in postmenopausal less than 2 years), it is necessary to confirm the negative result of the pregnancy test before treatment begins. Women capable of childbirth should fully explain the risks and carefully instruct the use of the most effective methods of contraception with their partners during administration of the drug and within 1 month after its end (condom with spermicide). If you assume a possible pregnancy, you should immediately cancel your medication and consult your doctor.
2. When distributed in the human body, CORONAVIR gets into sperm. When prescribing the drug to male patients, it is necessary to fully explain the risks and carefully instruct the use of the most effective methods of contraception in sexual contact during administration of the drug and within 3 months after its end (condom with spermicide). Additionally, it is necessary to instruct male patients not to have sexual contact with pregnant women.
3. When distributed in the human body, CORONAVIR enters breast milk. When prescribing the drug to lactating women, it is necessary to fully explain the risks and carefully instructed to stop breastfeeding during the drug and within 7 days after its end.

Care should be taken when driving vehicles and working with mechanisms.

Film-coated tablets, 200 mg.

50 tablets per polymer jar (polyethylene) for medicines, sealed with a polymer lid (polypropylene) with the control of the first opening.

A label made of label or writing paper or a self-adhesive label is glued to the jar.

Each jar, together with instructions for use, is placed in a pack of boxed cardboard.

At a temperature not exceeding 25 °C.

Keep out of reach of children.

1 year. Do not apply after the expiration date.