Betadine®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT BETAIDIN® (BETADINE®)

Composition:

Active ingredient: povidone-iodine;

1 vaginal suppository contains 200 mg povidone-iodine (corresponds to 17–24 mg of active iodine);

Excipients: macrogol 1000.

Dosage form. Vaginal suppositories.

Main physicochemical properties: torpedo-shaped, homogeneous, dark brown suppositories with an iodine odor.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents used in gynecology. ATC code G01AX11.

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 potent bactericidal effect and has a broad antimicrobial spectrum of 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 skin and mucous membranes, a significant amount of iodine is 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, thereby inactivating or destroying these proteins. Most microorganisms are destroyed 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, and thus the fading of the brown color intensity serves as an indicator of its effectiveness.

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

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

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

Prolonged application of the drug to large wound surfaces or severe burns, as well as to mucous membranes, may lead to the 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 hormone status.

Pharmacokinetics.

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.

Absorption of povidone-iodine or iodide is comparable 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 excreted 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 of iodine per 1 g of creatinine).

Clinical characteristics.

Indications.

Acute and chronic vaginal infections (colpitis):

• mixed infections;
• nonspecific infections (bacterial vaginosis caused by Gardnerella vaginalis);
• fungal infections (Candida albicans);
• vaginal infections following treatment with antibiotics and steroid drugs;
• trichomoniasis (in such cases, combined systemic treatment should be administered if necessary).

Preoperative prophylaxis in surgical procedures involving the vagina or diagnostic procedures.

Contraindications.

• Hypersensitivity to iodine or suspected hypersensitivity, or to any of the excipients.
• Patients with thyroid dysfunction (nodular colloid goiter, endemic goiter, and Hashimoto's thyroiditis).
• Patients with hyperthyroidism or other acute thyroid disorders.
• Before and after radioactive iodine therapy or 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 within a pH range of 2–7.

Concurrent use of PVP-iodine and hydrogen peroxide, as well as enzymatic preparations containing silver or taurolidine, for wound treatment or antiseptics, leads to mutual reduction in efficacy.

Application of povidone-iodine simultaneously or immediately after antiseptics containing octenidine may result in the development of dark necrotic lesions at the site of application.

PVP-iodine must not be used with mercury-containing preparations due to the risk of forming mercuric iodide. The preparation may react with proteins and unsaturated organic compounds; therefore, the effect of PVP-iodine may be reduced, necessitating an increase in dosage.

Prolonged use of the preparation should be avoided in patients receiving lithium therapy.

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

Special precautions for use.

The use of PVP-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), thereby making it impossible to plan treatment of thyroid disorders with iodine-containing medications.

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

The product must 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 induce hyperthyroidism in patients with thyroid dysfunction (e.g., nodular colloid goiter, endemic goiter). Therefore, application of the ointment should be limited in duration and in the surface area of skin treated.

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

The oxidizing effect of PVP-iodine may cause corrosion of metals, whereas plastics and synthetic materials are generally resistant to PVP-iodine. In individual 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.

Excessive intake of iodine may cause hyperthyroidism in patients with thyroid disorders. The use of Betadine® vaginal suppositories should be as short as possible in such patients. Thyroid function tests should be performed if symptoms of hyperthyroidism occur after treatment.

The regular use of Betadine® vaginal suppositories should be avoided in patients receiving lithium medications.

The oxidizing action 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).

Use during pregnancy or breastfeeding.

Povidone-iodine should be used only when strictly prescribed by a physician and in the smallest possible doses. Iodine crosses the placental barrier and is excreted in breast milk, thus posing a potential 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. It is necessary to monitor thyroid function in infants.

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

Fertility.

The drug has a spermicidal effect and therefore is not recommended for use in women planning pregnancy.

Ability to affect reaction rate while driving or operating machinery.

Betadine® vaginal suppositories do not affect the ability to drive or operate machinery.

Method of Administration and Dosage

The medication is intended for vaginal use.

It is recommended to use the medication once daily for 7 days.

In more severe infections, treatment may be extended for an additional 7 days. In persistent infections, the medication may be administered twice daily (after consultation with a physician).

Remove the suppository from its wrapper, moisten it with water, and insert deeply into the vagina.

During treatment with suppositories, the use of sanitary pads is recommended.

Method of Insertion:

Insert 1 vaginal suppository deeply into the vagina in the evening before bedtime. The medication should be used daily (even during menstruation).

Children

Betadine® vaginal suppositories are not intended for use in children.

Overdose

Symptoms 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 insufficiency;
• laryngeal edema with secondary asphyxia, pulmonary edema, metabolic acidosis, hypernatremia.

Treatment: symptomatic and supportive therapy should be administered, with careful monitoring of electrolyte balance, renal function, and thyroid gland function.

Adverse reactions.

Povidone-iodine is generally well tolerated. Local reactions are possible, although this substance is considered less irritating.

Immune system side effects: hypersensitivity, anaphylactic reactions.

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

If any of the above symptoms occur during treatment, use of the product should be discontinued immediately and medical advice should be sought.

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

Metabolism and nutrition disorders: electrolyte imbalance; metabolic acidosis.

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

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 long-term use of the product, primarily in patients with pre-existing thyroid disease.

Adverse effects from other organs and systems have been reported only sporadically.

Suppositories have a spermicidal effect; therefore, their use is not recommended for individuals planning pregnancy.

In isolated cases, generalized acute reactions with decreased blood pressure and/or difficulty breathing (anaphylactic reactions) may occur.

Shelf life: 3 years.

Storage conditions.

Store in a refrigerator at 5±3 °C, in a place inaccessible to children.

Packaging.

7 suppositories per blister; 1 or 2 blisters per cardboard box.

Availability category: Over-the-counter (without prescription).

Manufacturer.

EGIS Pharmaceuticals Ltd., Hungary.

Manufacturer's address and place of business:

65 Matyas kiraly Street, Kormend, 9900, Hungary.