BETAVID

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BETAVID (BETAVID)

Composition:

Active substance: povidone-iodine;

1 ml of the preparation contains 100 mg of povidone-iodine;

Excipients: nonoxinol 9, glycerol, citric acid anhydrous, sodium hydrogen phosphate anhydrous, sodium hydroxide, purified water.

Pharmaceutical form. Topical solution 100 mg/ml.

Main physicochemical properties: dark brown solution with an iodine odor, free from suspended or precipitated particles.

Pharmacotherapeutic group. Antiseptics and disinfectants. Povidone-iodine.

ATC code D08AG02.

Pharmacological Properties

Pharmacodynamics

Povidone-iodine is a complex of iodine and the polymer polyvinylpyrrolidone (PVP), which releases iodine gradually over a certain period after application to the skin. Free elemental iodine exerts a potent bactericidal effect and has a broad spectrum of antimicrobial activity against bacteria, viruses, fungi, and protozoa.

Mechanism of action: free iodine provides a rapid bactericidal effect, while the polymer acts as an iodine reservoir.

Upon contact with the skin and mucous membranes, a significant amount of iodine is released from the polymer.

When complexed with PVP, iodine largely loses the local irritant properties characteristic of alcoholic iodine solutions, thus being well tolerated by the skin, mucous membranes, and affected surfaces.

Iodine reacts with oxidizable sulfhydryl (SH–) and hydroxyl (OH–) groups of amino acids present in enzymes and structural proteins of microorganisms, inactivating or destroying these proteins. Most microorganisms are killed in vitro within less than one minute, with the primary destructive effect occurring within the first 15–30 seconds. During this process, iodine becomes decolorized; therefore, a change in the intensity of the brown color serves as an indicator of its efficacy.

The active ingredient of the drug BETAVID, topical solution, has a broad antimicrobial spectrum of activity: it acts against Gram-positive and Gram-negative bacteria (bactericidal), viruses (virucidal), fungi (fungicidal), fungal spores (sporicidal), as well as certain protozoa (antiprotozoal).

Due to its mechanism of action, resistance to the drug—including secondary resistance during prolonged use—is not expected.

The preparation is water-soluble and easily washed off with water.

Pharmacokinetics

Prolonged application of the drug to large wound surfaces or severe burns, as well as to mucous membranes, may lead to absorption of a significant amount of iodine. Typically, prolonged use results in a rapid increase in blood iodine levels. Concentrations return to baseline within 7–14 days after the last application.

In patients with normal thyroid gland function, increased iodine stores do not cause clinically significant changes in thyroid hormonal status.

Absorption and renal excretion of povidone-iodine depend on its molecular weight. Since the molecular weight ranges between 35,000 and 50,000, retention of the substance is possible.

The volume of distribution is approximately 38% of body weight. The biological half-life after vaginal administration is approximately 2 days. Normal total plasma iodine levels are approximately 3.8–6 µg/dL, while inorganic iodine levels are 0.01–0.5 µg/dL.

The drug is primarily excreted from the body via the kidneys, with a clearance rate of 15 to 60 mL/min, depending on plasma iodine levels and creatinine clearance (normal: 100–300 µg iodine per 1 g creatinine).

Clinical characteristics.

Indications.

Disinfection of hands and antiseptic treatment of mucous membranes, e.g. prior to surgical procedures, gynecological and obstetric procedures, urinary bladder catheterization, biopsy, injections, punctures, blood collection, as well as first aid in case of accidental skin contamination with infectious material.

Antiseptic treatment of wounds and burns.

Hygienic and surgical hand disinfection.

Contraindications.

Hypersensitivity to iodine or suspected hypersensitivity, or hypersensitivity to other components of the medicinal product.

Thyroid dysfunction (nodular colloid goiter, endemic goiter, and Hashimoto's thyroiditis).

Hyperthyroidism or other acute thyroid disorders.

The medicinal product is contraindicated before and after treatment and scintigraphy with radioactive iodine in patients with thyroid carcinoma.

Dermatitis herpetiformis Duhring.

Renal insufficiency.

Interaction with other medicinal products and other forms of interaction.

The povidone-iodine complex is active against microorganisms at pH 2–7. Due to its oxidizing properties, povidone-iodine may interfere with the results of certain diagnostic tests, such as occult blood tests in feces or urine, or urine glucose tests. When povidone-iodine is used, iodine uptake by the thyroid gland may be reduced, which may affect the results of certain diagnostic tests (e.g. thyroid scintigraphy, measurement of protein-bound iodine, or radioactive iodine uptake tests). Povidone-iodine may also interact antagonistically with iodine used in thyroid therapy. Medicinal products containing mercury, silver, hydrogen peroxide, or taurolidine may interact with the povidone-iodine complex; therefore, their concomitant use is not recommended. Povidone-iodine may react with proteins and unsaturated organic compounds, so the effect of povidone-iodine may be counteracted, requiring an increase in dose.

Simultaneous or immediate sequential application of povidone-iodine and antiseptics containing octenidine may lead to the development of dark necrosis at the application sites.

Povidone-iodine should not be used simultaneously with disinfectants containing chlorhexidine, hydrogen peroxide, taurolidine, silver sulfadiazine, mercury, or alkalis, due to the possibility of partial reduction in efficacy.

Concomitant topical application of povidone-iodine and benzoic tincture reduces pH, which may cause a burning sensation, especially if the wound is covered with a dressing.

Concomitant use of povidone-iodine and lithium-containing drugs may produce a synergistic hypothyroid effect.

Special precautions for use.

The use of povidone-iodine may reduce iodine uptake by the thyroid gland, which can affect the results of certain diagnostic tests and procedures (thyroid scintigraphy, protein-bound iodine determination, diagnostic procedures involving radioactive iodine), making it impossible to plan treatment of thyroid disorders with iodine-containing drugs. After discontinuation of povidone-iodine therapy, an interval of at least 1–4 weeks should be observed.

The drug should not be used in patients before or after treatment of thyroid cancer with radioactive iodine or after radioactive iodine scintigraphy.

Significant amounts of iodine may cause hyperthyroidism in patients with thyroid dysfunction (e.g., nodular colloid goiter, endemic goiter).

Even after completion of treatment, patients should be monitored for early symptoms of hyperthyroidism and thyroid function should be controlled.

The oxidizing effect of povidone-iodine may lead to false-positive results in diagnostic tests (e.g., toluidine and guaiac tests for hemoglobin and glucose in feces and urine).

The oxidizing effect of povidone-iodine may cause corrosion of metals, whereas plastic and synthetic materials are generally resistant to povidone-iodine. In some cases, discoloration may occur, which is usually reversible.

Povidone-iodine can be easily removed from textiles and other materials with warm water and soap. Stubborn stains should be treated with ammonia solution or sodium thiosulfate.

The solution is not intended for internal use.

During preoperative skin disinfection, care should be taken to ensure that no residual solution remains under the patient (due to possible skin irritation).

Since the development of hyperthyroidism cannot be ruled out, prolonged use of povidone-iodine (more than 14 days) or its use in large quantities over large body surface areas (over 10% of body surface) in patients (especially elderly patients) with latent thyroid dysfunction should only be permitted after careful assessment of expected benefit versus potential risk. Such patients should be monitored for early signs of hyperthyroidism and appropriate evaluation of thyroid function, even after discontinuation of the drug (up to 3 months).

Oropharyngeal administration may lead to the development of pneumonitis.

Discoloration of the solution indicates reduced efficacy of the medicinal product. Light and temperatures above 40°C accelerate the degradation of the active substance. The solution is intended for external use only.

Use during pregnancy or breastfeeding.

Povidone-iodine should be used only when strictly prescribed by a physician and at the lowest possible doses. Iodine crosses the placental barrier and may pass into breast milk, thus posing a risk of iodine hypersensitivity in the fetus or newborn. The concentration of povidone-iodine in breast milk is higher than in blood serum. Therefore, the drug may cause hyperthyroidism or elevated thyroid hormone levels in the fetus or newborn. Thyroid function in infants should be monitored.

The drug is contraindicated after the second month of pregnancy and during breastfeeding. Breastfeeding must be discontinued during treatment.

Ability to affect the speed of reactions while driving or operating machinery.

Unknown.

Method of Administration and Dosage

The product is intended for topical use in both diluted and undiluted form. The product must not be mixed with hot water. Only brief warming to body temperature is permissible.

Dosage

Undiluted BETAVID solution is used for disinfection of hands and skin prior to surgical procedures, urinary bladder catheterization, injections, and punctures.

The solution may be applied 2–3 times daily.

Hygienic hand disinfection: 2 applications of 3 mL of undiluted solution; each 3 mL dose remains on the skin for 30 seconds.

Surgical hand disinfection: 2 applications of 5 mL of undiluted solution; each 5 mL dose remains on the skin for 5 minutes.

For skin disinfection, the undiluted solution is applied and left on the skin until dry.

For the indications specified above, the solution may also be used after dilution with tap water. However, for surgical procedures and for antiseptic treatment of wounds and burns, 0.9% sodium chloride solution or Ringer's solution should be used for dilution.

Recommended dilutions are as follows:

The solution should be diluted immediately before use.

Children.

Povidone-iodine may be used in newborns and children under 1 year of age only under strict indications.

High doses of iodine should be avoided in newborns and young children, as their skin has higher permeability and increased sensitivity to iodine is more common, increasing the risk of developing hyperthyroidism. Povidone-iodine should be used in small doses in such patients. Thyroid function should be monitored in children if necessary.

Overdose.

Symptoms characteristic of acute iodine intoxication include:

• metallic taste in the mouth, increased salivation, burning sensation or pain in the mouth or throat;
• eye irritation and swelling;
• skin reactions;
• gastrointestinal disturbances and diarrhea;
• kidney dysfunction and anuria;
• circulatory failure;
• laryngeal edema with secondary asphyxia, pulmonary edema, metabolic acidosis, hypernatremia.

Prolonged treatment of burn wounds with significant amounts of povidone-iodine may lead to disturbances in electrolyte balance or serum osmolality, resulting in impaired kidney function or metabolic acidosis.

Treatment. Symptomatic and supportive therapy should be administered, with special attention to electrolyte balance, kidney function, and thyroid function.

In cases of intoxication due to accidental oral ingestion of the medicinal product, immediate administration of food products containing starch or protein (such as starch solution in water or milk) is indicated, followed by gastric lavage with 5 % sodium thiosulfate solution. If necessary, intravenous administration of 10 ml of 10 % sodium thiosulfate solution at 3-hour intervals is recommended. Monitoring of thyroid function is indicated for early detection of iodine-induced hyperthyroidism.

Adverse reactions.

Immune system disorders: hypersensitivity, anaphylactic reactions.

Renal and urinary system disorders: impaired kidney function, acute renal failure.

Skin and subcutaneous tissue disorders: local hypersensitivity skin reactions such as contact dermatitis with formation of psoriasiform red, small bullous lesions; allergic reactions including pruritus, erythema, rash, angioneurotic edema, exfoliative dermatitis, dry skin, chemical and thermal skin burns.

Endocrine system disorders: hyperthyroidism (sometimes with symptoms such as tachycardia or anxiety); hypothyroidism.

Metabolism and nutrition disorders: electrolyte imbalance, metabolic acidosis.

Prolonged use of povidone-iodine may lead to absorption of a large amount of iodine.

In some cases, iodine-induced hyperthyroidism has been reported following prolonged use of the product, mainly in patients with pre-existing thyroid disease.

In rare cases, generalized acute reactions with decreased blood pressure and/or respiratory distress (anaphylactic reactions) may occur.

Investigations: changes in serum electrolyte levels (hypernatremia) and osmolality, metabolic acidosis.

Reporting of adverse reactions after marketing authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

30 ml in a bottle, 1 bottle closed with a dropper cap or nozzle and cap, or dropper and cap, in a carton; 30 ml in a bottle, 1 bottle closed with a cap, in a carton with a dropper cap; 100 ml in a bottle, 1 bottle closed with a nozzle and cap or dropper and cap, in a carton; 1000 ml in a bottle closed with a cap; 1000 ml in a bottle closed with a dropper and cap.

Supply category. Over-the-counter.

Manufacturer.

JSC FF "Viola".

Manufacturer's location and address of its business activity.

75 Amosova St., Zaporizhzhia, Ukraine, 69063.