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Areplivir. Instructions. English

Registration number: 

LP-006288 

Trade name: 

AREPLIVIR 

International generic or group name: 

favipiravir 

Medicinal form: 

tablets covered with film shell 

Composition 

1 tablet: 

Active substance: 

Favipiravir – 200.0 mg 

Excipients: 

Povidon (K-30), silicon colloidal dioxide, low-replace hyprolosis, microcrystal cellulose (type 101), sprinklen, stearic acid. 

Film shell: 

The finished film coating of The Fallray®  03F220114 yellow giopromellosis, titanium dioxide, macrogol 4000 (Polyethylene glycol 4000), iron dye oxide yellow E172. 

Description: 

the tablets are round, two-boiled, covered with a light yellow film shell. On the cross-section, the nucleus is white or almost white. 

Pharmacotherapy group: 

antiviral 

ATX code: 

J05AX27 

Pharmacological properties 

Pharmacodynamics 

Противовирусная активность in vitro 

Favipiravir has antiviral activity against laboratory strains of influenza A and B viruses (half maximum effective concentration (EU50)0.014-0.55 micrograms/ml). 

For influenza A and B strains resistant to adamantan (amantadine rimantadine), oseltamivir or zinamivir, EU50  is 0.03-0.94 micrograms/ml and 0.09-0.83 micrograms/ml, influenza A virus strains (including strains resistant to adamantan, oseltamivir and zinamivir), such as type A swine flu and type A avian influenza, including highly pathogenic strains (including H5N1 and H7N9), EU50  is 0.06-3.53 micrograms/ml. 

For influenza A and B strains resistant to adamantan, oseltamivir and zinamivir, EU50  is 0.09-0.47 micrograms/ml; cross resistance is not observed. 

Favipiravir inhibits the SARS-CoV-2 virus, which causes a new coronavirus infection (COVID-19). EU50  in Vero E6 cells is 61.88 micromoles, which equates to 9.72 micrograms/ml. 

Mechanism of action 

Favipiravir is metabolized in cells up to the ribeliphosphata favipiravir (RTF favipiravir) and selectively inhibits RNA-dependent RNA polymerase involved in the replication of the influenza virus. RTF favipiravira (1000 micromol/L) did not show an inhibitory effect on human DNA, but showed an inhibitory action in the range of 9.1 to 13.5% per person and in the range of 11.7 to 41.2% on human DNA γ. The inhibitory concentration (IC50) RTF favipirvira for polymerase II human RNA was 905 micromole/L. 

Resistance 

After 30 peress in the presence of favipiravir, there was no change in the susceptibility of influenza A viruses to favipiravir, and resistance strains were also not observed. Clinical studies have not found the appearance of influenza viruses resistant to favipiravir. 

Pharmacokinetics 

Absorption 

Favipiravir is easily absorbed in the gastrointestinal tract. Maximum concentration time (Tmax)1.5 hours 

Distribution 

The binding to plasma proteins is about 54%. 

Metabolism 

Favipiravir is mainly metabolized – aldehydeoxidase and partially metabolized to a hydroxylated form of xanthinoxidase. RTF favipiravira is metabolized in cells. Of the other metabolites, besides hydroxylate, conjugate glucuronate was also recorded in human blood plasma and urine. 

Excretion 

In general, favipiravir is excreted by the kidneys in the form of active hydroxylate metabolite, a small amount in the same form. Half-life (T1/2)about 5 hours. 

Patients with liver dysfunction 

When taking favipirvir in mild to moderately mild and moderately severe liver failure (Class A and B by Child-Pugh classification), the increase in Cmax  and AUC was 1.5 times and 1.8 times, respectively, compared to healthy volunteers.max   

Patients with impaired kidney function 

In patients with moderate renal failure (SCF zlt;60 ml/min and 30 ml/min) residual concentration of favipirvir (Cthrough)increased by 1.5 times compared to patients without impaired kidney function. 

Indications for use 

Treatment of new coronavirus infection (COVID-19). 

Contraindications 

Increased sensitivity to favipiravira or any component of the drug AREPLIVIR. 

Hepatic insufficiency of severe severity (Class C by child-Pugh classification). 

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

Pregnancy or pregnancy planning. 

Breastfeeding period. 

Children under the age of 18. 

With caution 

Patients with gout and hyperuricemia in history (possibly increased uric acid levels in the blood and exacerbation of symptoms), in elderly patients, patients with mild and moderate severity (Class A and B according to the Classification of Child-Pugh), patients with moderate renal failure (SCF qlt;60 ml/min) 

Use in pregnancy and breastfeeding 

In preclinical studies of favipiravir in dosages similar to clinical or smaller, there was early-stage embryo death and teratogenicity. 

The drug ARIPLYVIR is not suitable for pregnant women, as well as men and women during pregnancy planning. When prescribing the drug ARIPLIVIIR women who are able to procreate (including in postmenopausal less than 2 years), it is necessary to confirm the negative result of the pregnancy test before treatment. 

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

When prescribing the drug ARIPLIVIIR nursing women should stop breastfeeding during the drug and for 7 days after its end, as the main metabolite favipiravir gets into breast milk. 

How to use and dose 

Inside, 30 minutes before the meal. The drug AREPLIVIR is prescribed in the hospital. 

Recommended dosing regimen: 

on the 1st day of 1,600 mg (8 tablets) twice a day, in 2-10 days for 600 mg (3 tablets) twice a day. 

The total duration of treatment is 10 days or until confirmation of the elimination of the virus, if it comes earlier (two consecutive negative results of PCR-study obtained at least 24 hours). 

Side effect 

In the clinical study of the drug ALEPRIVIR (interim report data) adverse reactions were observed in 9 patients out of 40 (22.5%), including an increase in the activity of alaninaminotransferase (ALT) in 5 (12.5%) patients, increased activity of aspartathaminetransferase (ACT) in 7 (17.5%) patients and increased activity of creatinfosphosphokinase in 1 (2.5%) Patient. These adverse reactions correspond to the known undesirable drug reactions of favipiravira, presented in Table 1. 

The assessment of the incidence of adverse reactions is based on who’s classification: very often (1/10); (1/100, zlt;1/10); Infrequently (1/1000, zlt;1/100); rarely (1/10,000, zlt;1/1000); very rarely (1/10,000); frequency is unknown (it is not possible to determine the frequency of the available data). 

Table 1. Unwanted reactions 

Organ classification Unwanted reactions 
Violations from the blood and lymphatic system often: neutropenia, leukopeniaredco: leukocytosis, monocytosis, reticulocytopenia 
 
Metabolic and nutrition disorders often: hyperuricemia, hypertriglyceridemia: glucoseuriaredco: hypokalemia 
 
 
Disorders on the part of the immune system infrequently: rash: eczema, itching 
 
Disturbances on the part of the respiratory system, chest organs and mediastination rare: bronchial asthma, sore throat, rhinitis, nasopharyngitis 
Gastrointestinal disorders often: diarrhoea: nausea, vomiting, abdominal pain: abdominal discomfort, duodenal ulcer, spotting stool, gastritis 
 
 
Disorders on the part of the liver and bile ducts often: increased ALT activity, increased ACT activity, increased activity of gamma-glutamyltransferase (GGT): increased activity of alkaline phosphatase (HF), increased concentration of bilirubin in the blood 
 
Other rarely: abnormal behavior, increased activity of creatinfosfokinase (CFC), hematuria, larynx polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, headcutting, chest pain 

Overdose 

There are no reports of an overdose of favipiravir. 

Interaction with other drugs 

The drug AREPLIVIR is not metabolized by the cytochrome P450, mainly metabolized by aldehydeoxidase and partly xanthinoxaza. The drug AREPLIVIR inhibits aldehydeoxidase and cytochrome CYP2C8, but does not induce cytochrome P450. 

Table 2. Interdric interactions 

Medicinals 
 
Signs, symptoms and treatment Mechanism of action and risk factors 
Pyrazinamide Hyperuricemia In addition, the reabsorbion of uric acid in the renal tubules increases. 
Reaglinid May increase the concentration of retaglinide in the blood, possibly the development of undesirable reactions to retaglinide Inhibition of CYP2C8 leads to an increase in the concentration of retaglinide in the blood. 
Theophylline Concentration of favipiravir in the blood may increase, possibly the development of undesirable reactions to favipiravir Interaction with xanthinoxidase can lead to increased concentration of favipiravir in the blood 
Famcyclovir, Sulindak The effectiveness of these drugs can be reduced Inhibition of favipiravir by aldehydeoxidase can lead to a decrease in the concentration of active forms of these drugs in the blood. 

Special instructions 

The use of the drug is possible only in the conditions of inpatient medical care. 

In the development of side-effects, it is necessary to report this in due course for the implementation of pharmaceutical surveillance activities. Before taking the drug AREPLIVIR should provide written information to the patient about 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 for the use of the drug. 

Since animal studies have shown the death of embryos and teratogenicity, the drug AREPLIVIR cannot be prescribed to pregnant and presumably pregnant women. 

  1. When prescribing the drug AREPLIVIR to women, women who are able to give birth (including in postmenopausal less than 2 years) need to confirm the negative result of the pregnancy test before the start of treatment. 
  1. When the drug is distributed in the human body, AREPLIVIR gets into the sperm. When prescribing the drug to patients, men need to fully explain the risks and carefully instruct to use the most effective methods of contraception during sexual contact during the drug and within 3 months after its completion (condom with spermicide). In addition, it is necessary to instruct male patients not to have sexual contact with pregnant women. 
  1. When the drug AREPLIVIR is distributed in the human body, it enters breast milk. When prescribing the drug to nursing women should fully explain the risks and carefully instruct to stop breastfeeding at the time of taking the drug and for 7 days after its end. 

Impact on the ability to drive vehicles, mechanisms 

Caution should be exercised when driving and working with machinery. 

Release form 

Tablets covered with film shell, 200 mg. 

10 tablets in contour cell packaging made from polyvinyl chloride and foil film aluminum lacquered or from film polyvinyl chloride/polyviniliden chloride and aluminum printed lacquered foil. 

40, 100 tablets in a jar of high-density polyethylene, capped with a lid of polypropylene with the control of the first autopsy. The free space in the jar is filled with cotton medical hygroscopic. Each jar or 4 contouring cell packages, together with the medical application instructions, are placed in a pack of cardboard. 

Storage conditions 

At a temperature not higher than 25 degrees Celsius in a secondary package. 
 

Expiration date 

2 years. 
 

Vacation conditions 

They’re being released on prescription. 

Registration card holder 

PROMOMED RUS LLC, Russia129090, Moscow, Mira Avenue, House 13, Building 1, Office 13. 
 

Manufacturer 

Biochemist, Russia Legal Address: 430030, Republic of Mordovia, Saransk, Vasenko Street, 15AADelines of production: 430030, Republic of Mordovia, Saransk, Vasenko Street, 15A 
 
 

An organization that accepts consumer claims 

PROMOMED RUS LLC, Russia129090, Moscow, Mira Avenue, House 13, Building 1, Office 13 
 

June 26, 2020