Flavovir

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLAVOVIR® (FLAVOVIR®)

Composition:

1 ml of drops contains 1 ml of liquid extract Proteflazid (flavonoid content 0.85 mg/ml expressed as rutin, content of carboxylic acids not less than 0.30 mg/ml expressed as malic acid) from the herb of Deschampsia caespitosa L. and the herb of Calamagrostis epigeios L. (1:1).

Extraction solvent: ethanol 96%.

Pharmaceutical form. Drops.

Main physicochemical properties: dark green liquid with a specific odor.

Pharmacotherapeutic group.

Direct-acting antiviral agents. ATC code J05A X.

Immunostimulants. ATC code L03A X.

Pharmacological properties.

Pharmacodynamics.

Flavonoids contained in the medicinal product have the ability to inhibit replication of DNA- and RNA-viruses both in vitro and in vivo. In preclinical and clinical studies, the drug demonstrated inhibitory activity against influenza viruses, acute respiratory infections, and herpes viruses.

It has been proven that the mechanism of direct antiviral action involves inhibition of synthesis of virus-specific enzymes—DNA- and RNA-polymerases, thymidine kinase, reverse transcriptase, 3CL-protease, neuraminidase—and induction of endogenous interferon synthesis.

The flavonoids in the drops inhibit the activity of SARS-CoV-2 coronavirus 3CL-protease, as confirmed by molecular docking methods and using an assay kit containing MBP-tagged (maltose-binding protein) SARS-CoV-2 coronavirus 3CL-protease.

Using a dual Renilla luciferase reporter gene assay (modeling replication of seasonal coronavirus CoV-229E), inhibition was demonstrated.

Preclinical in vitro studies on Vero E6 and A549/ACE2 cell cultures demonstrated antiviral activity against the pandemic human coronavirus SARS-CoV-2, with significant suppression of viral replication.

The drug protects mucous membranes of the upper respiratory tract by normalizing local immunity parameters (lactoferrin, sIgA, and lysozyme).

Studies have shown that the drug normalizes synthesis of endogenous α- and γ-interferons to physiologically active levels, thereby enhancing the body's nonspecific resistance to viral and bacterial infections.

Clinical studies have shown that, when the medicinal product is taken daily according to age-related dosing and administration regimens, immune system refractoriness does not develop: no suppression of α- and γ-interferon synthesis is observed. This property of Flavovir® drops supports maintenance of interferon levels sufficient for an adequate immune response to infectious agents. This, in turn, allows prolonged use of the drug when necessary.

The medicinal product has antioxidant activity, inhibits free-radical processes, thereby preventing accumulation of lipid peroxidation products, enhances cellular antioxidant status, reduces intoxication, and promotes recovery after an infection and adaptation to adverse environmental conditions.

The drug acts as a modulator of apoptosis: it enhances the action of apoptosis-inducing factors by activating caspase-9, promoting faster elimination of virus-infected cells and primary prevention of chronic diseases arising on the background of latent viral infections.

Pharmacokinetics.

The active substances of the medicinal product are rapidly absorbed from the gastrointestinal tract into the blood, reaching maximum concentrations within 20 minutes after administration (in vivo studies). Based on the observed dynamics, the elimination half-life from blood plasma is approximately 2.3 hours. Bioavailability after oral administration is 80%. Elimination from the body is slow. The level of accumulation of active substances in blood cells is significantly higher compared to plasma. Sustained concentrations of active substances ensure prolonged drug action in the body and accumulation in organs and tissues due to release from blood cells. This pharmacokinetic profile of accumulation and release of active substances by blood cells necessitates twice-daily administration of the medicinal product to achieve effective concentrations.

Clinical characteristics.

Indications.

• Etiotropic treatment and prevention of acute respiratory viral infections (ARVI);
• etiotropic treatment and prevention of influenza, including that caused by pandemic strain viruses.

Contraindications.

Hypersensitivity to the components of the drug. Exacerbation of gastric or duodenal peptic ulcer. Autoimmune diseases.

Interaction with other medicinal products and other types of interactions.

During clinical use, the possibility of combining Flavovir® with antibiotics and antifungal agents for the treatment of viral-bacterial and viral-fungal infections has been established. No negative effects due to interaction with other medicinal products have been observed.

Special precautions for use.

For patients with chronic gastroduodenitis, in case of exacerbation of gastroduodenitis or development of gastroesophageal reflux, the medication should be taken 1.5–2 hours after eating.

This medicinal product contains no less than 85 vol. % ethanol (alcohol), i.e., from 27.2 mg/dose (for children from birth up to 1 year of age) to 408 mg/dose (for children aged 12 years and older and adults), equivalent to 0.7 ml of beer, 0.3 ml of wine (for children from birth up to 1 year of age) up to 10 ml of beer, 4 ml of wine (for children aged 12 years and older and adults) per dose.

Harmful for patients suffering from alcoholism. Caution is advised when administering to pregnant and breastfeeding women, children, patients with liver disorders, and patients with epilepsy.

Use during pregnancy or breastfeeding.

Preclinical studies have not revealed teratogenic, mutagenic, embryotoxic, fetotoxic, or carcinogenic effects. Clinical experience with the use of the medicinal product during the first, second, and third trimesters of pregnancy and during breastfeeding has not shown any negative effects. However, the principles of medicinal product prescription during pregnancy or breastfeeding should be followed, assessing the benefit-risk ratio and consulting a physician.

Ability to influence reaction rate when driving or operating machinery.

No negative effect on the ability to perform potentially hazardous activities requiring special attention and rapid reactions has been observed.

Method of administration and dosage.

Before use, the vial must be shaken.

The medication is dosed using a dropper. The required amount of the medication should be dropped into water (volume of water – 1–2 tablespoons), and taken 10–15 minutes before meals.

Dosage of the medicinal product

For the treatment of influenza and acute respiratory viral infections (in uncomplicated cases), Flavovir®, drops, should be used for 5 days. To achieve maximum therapeutic efficacy, Flavovir® drops should be started at the first signs of illness or after contact with infected individuals. Depending on the course of the disease, the treatment course may be extended up to 2 weeks.

For the prevention of influenza and acute respiratory viral infections, Flavovir®, drops, should be used for 1 to 4 weeks at a dose equal to half the therapeutic dose.

During an epidemic of pandemic strains, the duration of Flavovir®, drops, used for prophylaxis, may be extended up to 6 weeks.

In case of bacterial complications of influenza and other acute respiratory viral infections, to normalize immune system parameters, Flavovir®, drops, may be used for 4 weeks or longer.

Children.

Flavovir® can be used in children from birth.

Overdose.

Cases of overdose are unknown. In case of overdose, seek medical advice immediately.

Side effects.

Allergic reactions: in individuals with increased sensitivity, hypersensitivity reactions may occur. Allergic reactions may include rash, itching, skin swelling, urticaria, skin hyperemia.

Gastrointestinal disorders: gastrointestinal disturbances may occur – epigastric pain, nausea, vomiting, diarrhea (if these symptoms are present, the drops should be taken 1.5–2 hours after eating). In patients with chronic gastroduodenitis, exacerbation of gastroduodenitis and development of gastroesophageal reflux (reflux esophagitis) are possible.

General disorders: transient increase in body temperature up to 38 °C on days 3–10 of treatment, headache.

In case of any adverse reactions, consult a physician.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua ».

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze! Formation of a gel-like structure is acceptable, which breaks down upon shaking. Keep out of reach of children.

Packaging.

Amber glass bottles of 10 ml, 30 ml, 50 ml, closed with a cap and dropper plug with tamper-evident seal or with a child-resistant cap and dropper plug with tamper-evident seal, in a cardboard box.

Availability.

Over-the-counter.

Manufacturer.

LLC "NVC "Ecofarma", Ukraine.

Manufacturer's location and address of business activity.

Ulashanivka village, Shepetivka district, Khmelnytska region, 116, Shevchenko St., 30070, Ukraine.

Marketing Authorization Holder.

LLC "NVC "Ecofarma".

Address of the Marketing Authorization Holder.

136-B, Naberezhno-Korchuvatska St., Kyiv, 03045, Ukraine.