Coronavir (Tablets) Instructions for Use

Marketing Authorization Holder

Technology Lekarstv LLC (Russia)

Manufactured By

R-Pharm JSC (Russia)

Labeled By

R-PHARM, JSC (Russia)

Or

ORTAT, JSC (Russia)

Quality Control Release

R-PHARM, JSC (Russia)

ATC Code

J05AX27 (Favipiravir)

Active Substance

Favipiravir (Rec.INN registered by WHO)

Dosage Form

Coronavir

Film-coated tablets, 200 mg: 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light yellow with a brownish tint, round, biconvex; on the cross-section, the tablet core is from white to light yellow.

Excipients: microcrystalline cellulose 101, colloidal silicon dioxide, povidone K25, crospovidone, sodium stearyl fumarate.

Film coating composition Opadry II 85F220031 yellow [polyvinyl alcohol, titanium dioxide, macrogol 4000, talc, iron oxide yellow dye].

10 pcs. – blister packs (5) – cardboard packs.
50 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

Antiviral agent. Favipiravir inhibits the SARS-CoV-2 virus, which causes the new coronavirus infection (COVID-19). The EC₅₀ in Vero E6 cells is 61.88 µmol, which corresponds to 9.72 µg/ml.

It has antiviral activity against laboratory strains of influenza A and B viruses (EC₅₀ 0.014-0.55 µg/ml).

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

Pharmacokinetics

After oral administration, Favipiravir is readily absorbed from the gastrointestinal tract. T_max is 1.5 hours. With single intravenous administration of favipiravir in the dose range of 400-1800 mg, T_max ranges from 1.85 to 2.05 hours. Plasma protein binding is about 54%. When distributed in the human body, Favipiravir enters the semen. Favipiravir is mainly metabolized by aldehyde oxidase and partially metabolized to a hydroxylated form by xanthine oxidase. In cells, it is metabolized to Favipiravir RTP. Among other metabolites, besides the hydroxylate, the glucuronate conjugate was also detected in human plasma and urine. It is excreted mainly by the kidneys as the active hydroxylate metabolite, a small amount is excreted unchanged. T_1/2 is about 5 hours.

Indications

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

ICD codes

Dosage Regimen

Used in a hospital setting.

Orally, depending on body weight – at a dose of 1.6-1.8 g on the 1st day, then 600-800 mg 2 times/day from the 2nd to the 10th day.

Intravenous drip – 1.6 g 2 times/day on the 1st day of therapy, then 800 mg 2 times/day from the 2nd to the 10th day of therapy.

The total duration of the treatment course is 10 days or until confirmation of virus elimination if it occurs earlier (two consecutive negative PCR test results obtained at least 24 hours apart).

Adverse Reactions

Blood and lymphatic system disorders often – neutropenia, leukopenia; rarely – leukocytosis, monocytosis, reticulocytopenia.

Metabolism and nutrition disorders often – hyperuricemia, hypertriglyceridemia; infrequently – glucosuria; rarely – hypokalemia.

Immune system disorders infrequently – rash; rarely – eczema, pruritus.

Respiratory, thoracic and mediastinal disorders rarely – bronchial asthma, sore throat, rhinitis, nasopharyngitis.

Gastrointestinal disorders often – diarrhea; infrequently – nausea, vomiting, abdominal pain; rarely – abdominal discomfort, duodenal ulcer, bloody stool, gastritis.

Hepatobiliary disorders often – increased ALT, AST, GGT activity; rarely – increased ALP activity, increased blood bilirubin concentration.

Other rarely – abnormal behavior, increased CPK activity, hematuria, laryngeal polyp, hyperpigmentation, taste disorder, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain.

Contraindications

Hypersensitivity to favipiravir; severe hepatic impairment (Child-Pugh class C); severe renal impairment and end-stage renal disease (GFR<30 ml/min); pregnancy, pregnancy planning, breastfeeding period; children under 18 years of age.

With caution

Patients with a history of gout and hyperuricemia (possible increase in uric acid levels and exacerbation of symptoms), elderly patients, patients with mild to moderate hepatic impairment (Child-Pugh class A and B), patients with moderate renal impairment (GFR<60 ml/min and ≥30 ml/min).

Use in Pregnancy and Lactation

Contraindicated during pregnancy, when planning pregnancy, and during breastfeeding.

When distributed in the human body, Favipiravir enters the semen.

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

Additionally, it is necessary to instruct male patients not to engage in sexual contact with pregnant women.

If a possible pregnancy is suspected, it is necessary to immediately discontinue the use of this drug and consult a doctor.

If use during lactation is necessary, breastfeeding should be discontinued during treatment with favipiravir and for 7 days after its completion, because the main metabolite of favipiravir is excreted in breast milk.

Use in Hepatic Impairment

Contraindications: severe hepatic impairment (Child-Pugh class C).

With caution: patients with mild to moderate hepatic impairment (Child-Pugh class A and B).

Use in Renal Impairment

Contraindications: severe renal impairment and end-stage renal disease (GFR<30 ml/min).

With caution: patients with moderate renal impairment (GFR<60 ml/min and ≥30 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use is possible only in a hospital setting.

If adverse reactions occur, they must be reported in the established manner for pharmacovigilance measures.

Effect on ability to drive vehicles and operate machinery

Caution should be exercised when driving vehicles and working with machinery.

Drug Interactions

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

When used concomitantly with pyrazinamide, hyperuricemia is observed due to an additional increase in uric acid reabsorption in the renal tubules.

When used concomitantly with repaglinide, an increase in the blood concentration of repaglinide and the development of adverse reactions due to the action of repaglinide are possible.

When used concomitantly with theophylline, an increase in the plasma concentration of favipiravir and the development of adverse reactions to Favipiravir are possible.

When used concomitantly with famciclovir, sulindac, a decrease in their effectiveness is possible due to inhibition of aldehyde oxidase by favipiravir, which may lead to a decrease in the concentration of active forms of these substances in the blood.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.