Expiration date: 01/2025

Release form and composition for 1 tablet:

Active substance: Favipiravir - 200.0 mg

Auxiliary substance:

Povidone (K-30), colloidal silicon dioxide, low-substituted hyprolose, microcrystalline cellulose (type 101), crospovidone, stearic acid.

Film coating:

finished film coating Opadray ® 03F220114 yellow [Hypromellose, titanium dioxide, macrogol 4000 (polyethylene Glycol 4000), iron oxide yellow dye E172].

Pharmacotherapeutic group: antiviral agent

Pharmacological properties

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 mcg/ml).

For strains of influenza A and B viruses that are resistant to adamantane (amantadine rimantadine), oseltamivir or zanamivir, the EC50 is 0.03-0.94 mcg/ml and 0.09-0.83 mcg/ml, respectively. For influenza A virus strains (including strains resistant to adamantane, oseltamivir and zanamivir), such as swine flu type A and avian flu type A, including highly pathogenic strains (including H5N1 and H7N9), the EC50 is 0.06-3.53 micrograms/ml.

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

Favipiravir inhibits the SARS-CoV-2 virus, which causes a new coronavirus infection (COVID-19). the EC50 in Vero E6 cells is 61.88 mmol, which corresponds to 9.72 mcg/ml.

Mechanism of action

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

Resistance

After 30 replants in the presence of favipiravir, there were no changes in the susceptibility of influenza A viruses to favipiravir, and no resistant strains were observed. In the conducted clinical studies, the appearance of influenza viruses resistant to favipiravir was not detected.

Instructions for children and pregnant women

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

Areplivir the drug is contraindicated in pregnant and women and men during pregnancy planning. When prescribing the drug AREPLIVIR to women who are capable of childbearing (including postmenopausal women less than 2 years old), it is necessary to confirm a negative pregnancy test result before starting treatment. A second pregnancy test should be performed after the end of taking the drug.

It is necessary to use effective methods of contraception (a condom with spermicide) during and after taking the drug: for 1 month for women and for 3 months for men.

When prescribing the drug AREPLIVIR, nursing women should stop breastfeeding while taking the drug and within 7 days after it ends, since the main metabolite of favipiravir enters breast milk.

Pharmacokinetics

Absorption

favipiravir is easily Absorbed in the gastrointestinal tract. Time to reach the maximum concentration (Tmax) 1.5 hours.

The distribution

Of binding to plasma proteins is about 54 %.

Metabolism

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

Breeding

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

Patients with impaired liver function

When taking favipiravir in patients with mild to moderate hepatic insufficiency (class A and B according to the child-Pugh classification), the Cmax and AUC increases were 1.5 times and 1.8 times, respectively, compared with healthy volunteers. These increases in Cmax and AUC for patients with severe hepatic insufficiency (class C according to the child-Pugh classification) were 2.1 times and 6.3 times, respectively.

Patients with impaired renal function

In patients with moderate renal insufficiency (GFR <60 ml/min and ?30 ml/min), the residual concentration of favipiravir (Cthrough) increased by 1.5 times compared to patients without impaired renal function. The drug has not been studied in patients with severe and terminal renal insufficiency (GFR <30 ml/min).

Special instruction

If a side effect develops, it is necessary to report it in accordance with the established procedure for the implementation of pharmacovigilance measures.

Since fetal death and teratogenicity have been observed in animal studies of favipiravir, AREPLIVIR should not be prescribed to pregnant and presumably pregnant women.

1) when prescribing the drug AREPLIVIR to women who are capable of childbearing (including postmenopausal women less than 2 years old), it is necessary to confirm a negative pregnancy test result before starting treatment. Women who are capable of childbearing should be fully explained the risks and carefully instructed to use the most effective methods of contraception with their partners while taking the drug and for 1 month after it ends (a condom with spermicide). If you assume that pregnancy may occur, you should immediately stop taking the drug and consult your doctor.

2) when distributed In the human body, favipiravir enters the sperm. When prescribing the drug to male patients, it is necessary to fully explain the risks and carefully instruct them to use the most effective methods of contraception during sexual contact during the drug intake and for 3 months after its end (a condom with spermicide). Additionally, male patients should be instructed not to have sexual contact with pregnant women.

3) when distributed In the human body, favipiravir enters breast milk. When prescribing the drug, nursing women should fully explain the risks and carefully instruct them to stop breastfeeding while taking the drug and within 7 days after it ends.

Influence on the ability to drive vehicles, mechanisms

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

Interaction

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

Overdose

There are no reports of favipiravir overdose.

How to take, course of administration and dosage

Inside, 30 minutes before meals.

For the treatment of new coronavir uses infection (COVID-19) caused by the virus SARS-CoV-2, we recommend the following dosing regimen:

• for patients with body weight <75 kg and 1600 mg (8 tablets), 2 times in the 1st day of therapy, then 600 mg (3 tablets) 2 times a day, respectively, from the 2nd to the 10th day of therapy;
• for patients with a body weight of ?75 kg, 1800 mg (9 tablets) 2 times on the 1st day of therapy, then 800 mg (4 tablets) 2 times a day, respectively, from the 2nd to the 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 results obtained at least 24 hours apart).

Contraindications

Hypersensitivity to favipiravir or any component of the drug Areplivir.

Severe hepatic insufficiency (class C according to the child - Pugh classification).

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

Pregnancy or pregnancy planning.

Breast-feeding period.

Children under 18 years of age.

With caution

Patients with a history of gout and hyperuricemia (possible increase in uric acid levels in the blood and exacerbation of symptoms), elderly patients, patients with mild to moderate hepatic insufficiency (class A and B according to the child-Pugh classification), patients with moderate renal insufficiency (GFR <60 ml/min and ?30 ml/min).

Areplivir indications for use

Treatment of new coronavirus infection (COVID-19).

Side effects

In a clinical study of the drug Areplivir frequency of patients with reported cases of adverse events made up 24.04% (25/104). An increase in alanine aminotransferase (ALT) activity was observed in 17.3% (18/104) of patients, an increase in aspartate aminotransferase (AST) activity in 12.5% (13/104), and an increase in creatine phosphokinase activity in 0.9% (1/104) of patients. These adverse reactions correspond to the known adverse drug reactions of favipiravir presented in Table 1.

The estimation of the frequency of adverse reactions is based on the who classification: very common (?1/10); common (?1/100, <1/10); infrequent (?1/1000, <1/100); rare (?1/10000, <1/1000); very rare (<1/10000); frequency unknown (it is not possible to determine the frequency from the available data).

Storage conditions

At a temperature not exceeding 25 ° C in the secondary packaging.