Areplivir (Favipiravir) 200 mg 40 tablets

indications for Areplivir (Favipiravir)

Russian product name:

Areplivir (favipiravir)

Release form:

Film-coated tablets

Description Areplivir:

Film-coated tablets of light yellow color, round, biconvex
in cross section, the core is white or almost white.

1 tab.
favipiravir 200 mg
Excipients: povidone K30, colloidal silicon dioxide, low-substituted hyprolose, microcrystalline cellulose (type 101), crospovidone, stearic acid.

The composition of the film shell: ready-made film coating Opadray ® 03F220114 yellow [hypromellose, titanium dioxide, macrogol 4000 (polyethylene glycol 4000), iron dye yellow oxide E172].

10 pieces. - contoured cell packaging (4) - cardboard packs.
40 pcs. - cans (1) - packs of cardboard.
100 pieces. - cans (1) - packs of cardboard.
Favipiravir

Clinical and pharmacological groups Areplivir:
Antiviral drug

Active substance:
Favipiravir For Covid

Pharmaco-therapeutic group Areplivir:

Antiviral agent

Storage conditions:

The drug Areplivir should be stored in secondary packaging out of the reach of children at a temperature not exceeding 25 ° C.

pharmachologic effect Areplivir:

Antiviral activity in vitro

Favipiravir has antiviral activity against laboratory strains of influenza A and B viruses (half maximum effective concentration (EC 50 ) 0.014-0.55 μg / ml).

For strains of influenza A and B viruses resistant to adamantane (amantadine, rimantadine), oseltamivir or zanamivir, the EC 50 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 type A swine influenza and type A avian influenza, including highly pathogenic strains (including H5N1 and H7N9), the EC 50 is 0.06-3.53 μg / ml.
For strains of influenza A and B viruses resistant to adamantane, oseltamivir and zanamivir, the EC 50 is 0.09-0.47 μg / ml; cross-resistance is not observed.
Favipiravir inhibits the SARS-CoV-2 virus, which causes the new coronavirus infection (COVID-19). The EC 50 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 ribosyl triphosphate (Favipiravir RTF) and selectively inhibits RNA-dependent RNA polymerase involved in influenza virus replication. RTF favipiravir (1000 μmol / L) showed no inhibitory effect on human αDNA, but showed an inhibitory effect in the range from 9.1 to 13.5% on β and in the range from 11.7 to 41.2% on human γDNA. The inhibitory concentration (IC 50 ) of RTF favipiravir for human RNA polymerase II was 905 µmol / L.

Resistance

After 30 passages in the presence of favipiravir, no changes were observed in the susceptibility of influenza type A viruses to favipiravir, and no resistant strains were observed either. In the clinical studies carried out, the appearance of influenza viruses resistant to favipiravir was not detected.

Indications Areplivir:

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

Method of application, course and dosage:

The drug Areplivir is taken orally, 30 minutes before meals.
For the treatment of novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus , the following dosing regimen is recommended:

for patients weighing <75 kg, 1600 mg (8 tablets) 2 times on the 1st day of therapy, then 600 mg (3 tablets) 2 times / day, respectively, from the 2nd to the 10th day therapy;
for patients weighing ≥75 kg, 1800 mg (9 tablets) 2 times on the 1st day of therapy, then 800 mg (4 tablets) 2 times / day, respectively, from the 2nd to the 10th day therapy.

The drug Areplivir 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 the course of treatment is 10 days or until confirmation of the elimination of the virus, if it occurs earlier (two consecutive negative results of PCR studies obtained with an interval of at least 24 hours).

Overdose Areplivir:

There are no reports of an overdose with favipiravir.

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

Drug-drug interactions:

Medicines Signs, symptoms and treatment Mechanism of action and risk factors

Pyrazinamide Hyperuricemia Additionally, the 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 an increase in the concentration of repaglinide in the blood
Theophylline The concentration of favipiravir in the blood may increase, possibly the development of adverse reactions to favipiravir Interaction with xanthine oxidase can lead to an increase in the concentration of favipiravir in the blood
Famciclovir, sulindak The effectiveness of these drugs Areplivir may be reduced Inhibition of aldehyde oxidase by favipiravir can lead to a decrease in the concentration of active forms of these drugs Areplivir in the blood

Application during pregnancy and lactation
In preclinical studies of favipiravir at doses similar to clinical ones or less, early embryo death and teratogenicity were observed.

Areplivir is contraindicated in pregnant women, as well as in men and women during pregnancy planning. When prescribing the drug Areplivir to women 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 repeated pregnancy test must be performed after the end of the drug intake. It is necessary to use effective methods of contraception (a condom with spermicide) while taking the drug and after it ends: within 1 month for women and within 3 months for men.

When prescribing Areplivir, breastfeeding women need to stop breastfeeding while taking the drug Areplivir and within 7 days after it ends. the main metabolite of favipiravir is excreted in breast milk.

Side effect Areplivir:

In a clinical study of Areplivir, the frequency of patients with reported cases of adverse events was 24.04% (25/104). An increase in ALT activity was observed in 17.3% (18/104) patients, an increase in ACT activity - in 12.5% (13/104) and an increase in CPK activity - in 0.9% (1/104) patients. These adverse reactions are consistent with the known adverse drug reactions of favipiravir described below.

Estimation of the incidence of unwanted adverse reactions is based on the WHO classification: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rare (<1/10000); the frequency is unknown (it is not possible to establish the frequency from the available data).
From the hematopoietic system: often - neutropenia, leukopenia; rarely - leukocytosis, monocytosis, reticulocytopenia.
From the side of metabolism: often - hyperuricemia, hypertriglyceridemia; infrequently - glucosuria; rarely, hypokalemia.
From the immune system: infrequently - rash; rarely - eczema, itching.
From the respiratory system: rarely - bronchial asthma, sore throat, rhinitis, nasopharyngitis.
From the digestive system: often - diarrhea; infrequently - nausea, vomiting, abdominal pain; rarely - abdominal discomfort, duodenal ulcer, bloody stools, gastritis.
From the liver and biliary tract: often - increased ALT activity, increased ACT activity, increased GGT activity; rarely - an increase in ALP activity, an increase in the concentration of bilirubin in the blood.

Others:
rarely - abnormal behavior, increased CPK activity, hematuria, laryngeal polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain.

Contraindications for use Areplivir:

hepatic impairment of severe severity (class C according to the Child-Pugh classification);
severe renal failure and end-stage renal failure (GFR <30 ml / min);
pregnancy or planning a pregnancy;
period of breastfeeding;
children and adolescents up to 18 years old;
hypersensitivity to favipiravir or any component of the drug Areplivir.
With caution: in patients with a history of gout and hyperuricemia (possibly an increase in the concentration of uric acid in the blood and exacerbation of symptoms); in elderly patients; in patients with mild to moderate hepatic impairment (class A and B according to Child-Pugh classification); in patients with moderate renal failure (GFR <60 ml / min and> 30 ml / min).

Special instructions Areplivir:

With the development of side effects, it is necessary to report this in the prescribed manner for the implementation of pharmacovigilance measures.
Because of the death of embryos and teratogenicity in animal studies of favipiravir, Areplivir should not be administered to pregnant and presumably pregnant women.

When prescribing Areplivir to women 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 fertile should be fully aware of the risks and carefully instructed on the use of the most effective contraceptive methods with their partners while taking the drug Areplivir and for 1 month after it ends (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, favipiravir enters the semen. When prescribing the drug to patients, men need to fully explain the risks and carefully instruct on the use of the most effective methods of contraception during sexual intercourse while taking the drug and within 3 months after its termination (condom with spermicide). Additionally, male patients should be instructed not to have sexual intercourse with pregnant women.

When distributed in the human body, favipiravir passes into breast milk. When prescribing the drug to lactating women, it is necessary to fully explain the risks and carefully instruct about stopping breastfeeding while taking the drug and within 7 days after it ends.
Influence on the ability to drive vehicles and mechanisms

Care should be taken when driving and operating machinery.

Application for impaired renal function
The use of the drug Areplivir is contraindicated in severe renal failure, incl. terminal stage.
The drug should be used with caution in patients with moderate renal insufficiency.

Application for violations of liver function
The use of the drug is contraindicated in severe hepatic failure.
The drug should be used with caution in patients with mild to moderate hepatic impairment.

Terms of sale
The drug is available by prescription.

Use in elderly patients
The drug should be prescribed with caution to elderly patients.

Application in children
The use of the drug under the age of 18 is contraindicated.

Nosology (ICD codes)
COVID-19