Betadine®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BETAIDINE® (BETADINE®)

Composition:

Active substance: povidone-iodine;

1 g of ointment contains 100 mg of povidone-iodine;

Excipients: macrogol 400, macrogol 4000, macrogol 1000, macrogol 1500, sodium hydrogencarbonate, purified water.

Medicinal form. Ointment.

Main physicochemical characteristics: homogeneous brown ointment with a faint iodine odor.

Pharmacotherapeutic group. Antiseptics and disinfectants.

ATC code D08AG02.

Pharmacological properties.

Pharmacodynamics.

Povidone-iodine is a complex of iodine and the polymer polyvinylpyrrolidone, which releases iodine gradually over a period of time after application to the skin. Free iodine exerts a 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, significant amounts of iodine are released from the polymer.

Iodine reacts with oxidative-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 is decolorized, so a change in the intensity of the brown color serves as an indicator of its effectiveness.

The active ingredient in Betadine® ointment has a broad antimicrobial spectrum of activity, including action against Gram-positive and Gram-negative bacteria (bactericidal), viruses (virucidal), fungi (fungicidal), fungal spores (sporicidal), as well as certain protozoa.

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.

Prolonged application of the preparation to large wound surfaces or severe burns, as well as to mucous membranes, may lead to the absorption of a significant amount of iodine. As a rule, prolonged use results in a rapid increase in blood iodine levels. Concentrations return to baseline levels 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 hormone status.

Pharmacokinetics.

Absorption and renal excretion of povidone-iodine depend on its molecular weight, which ranges between 35,000 and 50,000, potentially leading to retention of the substance.

Absorption of povidone-iodine or iodide is similar to that of iodine from other sources.

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

The drug is primarily eliminated 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 range: 100–300 µg iodine per 1 g creatinine).

Clinical characteristics.

Indications.

Prevention of infections in minor cuts and abrasions, minor burns, and minor surgical procedures.

Treatment of fungal and bacterial skin infections, as well as infections of pressure sores and trophic ulcers.

Contraindications.

• Hypersensitivity to iodine or suspected hypersensitivity, or to other components of the drug.
• Patients with thyroid gland function disorders (nodular colloid goiter, endemic goiter, and Hashimoto's thyroiditis).
• Patients with hyperthyroidism or other acute thyroid gland disorders.
• Before and after radioactive iodine treatment and scintigraphy 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.

Proteins and other organic compounds reduce its activity.

Concomitant use of Betadine® and enzymatic ointments for wound treatment reduces the efficacy of both preparations. Medicinal products containing mercury, silver, hydrogen peroxide, or taurolidine may interact with the povidone-iodine complex; therefore, their combined use is not recommended.

The use of povidone-iodine simultaneously or immediately after antiseptics containing octenidine may lead to the development of dark necroses at the application sites.

Caution!

Due to its oxidizing properties, povidone-iodine may interfere with the results of certain diagnostic tests, such as occult blood detection in feces or urine, or glucose detection in urine.

When povidone-iodine is used, iodine uptake by the thyroid gland may be reduced. This may affect the results of certain diagnostic tests (e.g., thyroid scintigraphy, determination of protein-bound iodine, measurement of radioactive iodine uptake), or may interfere with iodine administered for thyroid therapy.

Thyroid scintigraphy should be performed 1–2 weeks after discontinuation of prolonged therapy to obtain reliable results.

Special precautions for use.

The product is intended for topical use only.

Prolonged use may cause irritation and, occasionally, severe skin reactions. If signs of irritation or hypersensitivity occur, application of the product should be discontinued.

The use of PVP-iodine may reduce iodine uptake by the thyroid gland, which may 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.

A break of at least 1-4 weeks should be made in the use of PVP-iodine.

The product 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). Therefore, the duration of application and the skin surface area treated should be limited in such patients.

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

When applied over large skin areas for prolonged periods (e.g., extensive burns or wounds), a significant amount of iodine may be absorbed, potentially leading to hyperthyroidism in susceptible patients. A large skin area (defined as over 10% of body surface area) and treatment duration exceeding 14 days are considered prolonged therapy.

Iodine absorption varies individually for each patient, so precise recommendations are not available. Thyroid function tests and physicians' recommendations are crucial in such cases.

If symptoms of hyperthyroidism occur during treatment, thyroid function should be evaluated.

Particular attention should be paid to patients with pre-existing renal insufficiency when the ointment is used regularly.

Regular use of the ointment should be avoided in patients receiving lithium medications.

The oxidizing effect of PVP-iodine may cause corrosion of metals, whereas plastics and synthetic materials are generally resistant to PVP-iodine. In some cases, discoloration may occur, which is usually reversible. PVP-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 oxidizing action of povidone-iodine may lead to false-positive results in certain diagnostic tests (e.g., toluidine and guaiac tests for hemoglobin, and tests for glucose in feces and urine).

Do not heat before use. Keep out of reach of children.

Use during pregnancy or breastfeeding.

Povidone-iodine should be used only when strictly indicated by a physician and in the smallest possible doses. Iodine crosses the placental barrier and may pass into breast milk, thus posing a risk of hypersensitivity in the fetus or newborn to iodine. Povidone-iodine levels in breast milk are higher than in blood serum. Therefore, the product may cause hyperthyroidism or elevated thyroid hormone levels in the fetus or newborn. Thyroid function in infants should be monitored.

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

Ability to affect driving performance and operating machinery.

Betadine® ointment does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

Apply the preparation topically.

For treatment of infections: apply once or twice daily. The duration of treatment – no more than 14 days.

For prevention of infections: apply once or twice a week, as long as necessary. The affected skin must be cleaned and dried. Apply a thin layer of ointment to the affected skin area. A dressing may be applied over the treated area.

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 infants, as their skin is more permeable and they more frequently exhibit increased sensitivity to iodine, increasing the risk of developing hyperthyroidism. Povidone-iodine should be used in small amounts in such patients. If necessary, monitor thyroid gland function in children.

Overdose

Symptoms characteristic of acute iodine intoxication include:

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

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

Adverse reactions.

Immune system side effects: hypersensitivity, anaphylactic reactions.

Renal and urinary system side effects: renal function impairment, acute renal failure.

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

Endocrine system side effects: hyperthyroidism (sometimes with symptoms such as tachycardia or restlessness); 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, primarily in patients with pre-existing thyroid disease.

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

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

Shelf life: 3 years.

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

Storage conditions:

Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging:

20 g of 10% ointment in a tube; 1 tube per cardboard box.

Classification: Over-the-counter (no prescription required).

Manufacturer:

Egis Pharmaceuticals PLC, Hungary.

Manufacturer's address and place of business:

65 Matyas kiraly str., Kermend, 9900, Hungary.