International generic or group name:
tablets covered with film shell
Favipiravir – 200.0 mg
Povidon (K-30), silicon colloidal dioxide, low-replace hyprolosis, microcrystal cellulose (type 101), sprinklen, stearic acid.
The finished film coating of The Fallray® 03F220114 yellow giopromellosis, titanium dioxide, macrogol 4000 (Polyethylene glycol 4000), iron dye oxide yellow E172.
the tablets are round, two-boiled, covered with a light yellow film shell. On the cross-section, the nucleus is white or almost white.
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.
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.
Favipiravir is easily absorbed in the gastrointestinal tract. Maximum concentration time (Tmax)1.5 hours
The binding to plasma proteins is about 54%.
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.
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).
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.
Children under the age of 18.
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).
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|
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.|
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.
- 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.
- 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.
- 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.
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.
At a temperature not higher than 25 degrees Celsius in a secondary package.
They’re being released on prescription.
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PROMOMED RUS LLC, Russia129090, Moscow, Mira Avenue, House 13, Building 1, Office 13.
Biochemist, Russia Legal Address: 430030, Republic of Mordovia, Saransk, Vasenko Street, 15AADelines of production: 430030, Republic of Mordovia, Saransk, Vasenko Street, 15A
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PROMOMED RUS LLC, Russia129090, Moscow, Mira Avenue, House 13, Building 1, Office 13
June 26, 2020