Betadine

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

Composition:

Active substance: povidone-iodine;

1 ml of solution contains 100 mg of povidone-iodine;

Excipients: glycerol (85%), nonoxinol 9, citric acid anhydrous, sodium hydrogen phosphate anhydrous, sodium hydroxide, purified water.

Pharmaceutical form. Solution for external and local use.

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

Pharmacotherapeutic group. Antiseptics and disinfectants. Povidone-iodine.

ATX code D08AG02.

Pharmacological properties.

Pharmacodynamics.

Povidone-iodine is a complex of iodine and the polymer polyvinylpyrrolidone, which releases iodine gradually over a certain period after application to the skin. Free iodine exerts a strong 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 depot.

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

When forming a complex with PVP, iodine largely loses the local irritant effect typical of alcoholic iodine solutions, and therefore is well tolerated by the skin, mucous membranes, and affected surfaces.

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

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

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

The drug dissolves in water and is 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 absorption of a significant amount of iodine. Usually, prolonged use of the drug results in a rapid increase in blood iodine levels. The concentration returns 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. Since the molecular weight ranges between 35,000 and 50,000, substance retention is possible.

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 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 antisepsis of mucous membranes, e.g., prior to surgical procedures, gynecological and obstetric procedures, urinary catheterization, biopsy, injections, punctures, blood collection, as well as first aid in case of accidental contamination of the skin with infectious material.
• Antisepsis of wounds and burns.
• Hygienic and surgical hand disinfection.

Contraindications.

• Hypersensitivity to iodine or suspected hypersensitivity, or to other components of the medicinal product.
• Patients with thyroid gland dysfunction (nodular colloid goiter, endemic goiter, and Hashimoto's thyroiditis).
• Patients with hyperthyroidism or other acute thyroid disorders.
• 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.

Caution! Due to its oxidizing properties, povidone-iodine may interfere with the results of certain diagnostic tests, such as detection of occult blood in feces or urine, or glucose in urine. 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, determination of protein-bound iodine, measurement of radioactive iodine uptake), or may interfere with iodine administered for 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.

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

Povidone-iodine may react with proteins and unsaturated organic compounds; therefore, the effect of povidone-iodine may be reduced, necessitating an increase in dose.

Prolonged use should be avoided, especially over large areas, in patients receiving lithium medications.

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). Therefore, treatment of thyroid disorders with iodine-containing drugs may become impossible. 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 during radioactive iodine scintigraphy.

Significant amounts of iodine may cause hyperthyroidism in patients with impaired thyroid function (e.g. nodular colloid goiter, endemic goiter). Therefore, the use of the ointment should be limited in terms of duration and the skin surface area treated.

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 tests for glucose in feces and urine).

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

Povidone-iodine is 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 the potential for skin irritation).

Since the development of hyperthyroidism cannot be ruled out, prolonged use of povidone-iodine (more than 14 days) or its application in large quantities over extensive skin areas (exceeding 10% of body surface) in patients (particularly elderly patients) with latent thyroid dysfunction is permissible only after careful assessment of the 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 (for up to 3 months).

Oropharyngeal use may lead to the development of pneumonitis.

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 can 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. Evaluation of thyroid function in infants is necessary.

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

Ability to affect reaction speed when driving or operating machinery.

Unknown.

Method of Administration and Dosage

The medication is intended for external use in both diluted and undiluted forms.

The product must not be mixed with hot water. Only brief warming to body temperature is permissible.

Dosing.

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

Solutions 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 should be left on the skin until it dries.

For the indications listed above, the solution may also be used diluted 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: Table 1.

The solution should be diluted immediately before use.

Children.

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

High doses of iodine should be avoided in neonates and infants due to increased skin permeability and higher incidence of hypersensitivity to iodine, which increases the risk of hyperthyroidism. Povidone-iodine should be administered in small doses to such patients. If necessary, thyroid function should be monitored in children.

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;
• renal dysfunction and anuria;
• circulatory failure;
• laryngeal edema with secondary asphyxia, pulmonary edema, metabolic acidosis, hypernatremia.

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

Additionally, immediate administration of starch- and protein-containing products (e.g., starch solution in water or in milk). Gastric lavage using a 5% solution of sodium thiosulfate (or 10% sodium thiosulfate solution administered intravenously) at 3-hour intervals, if necessary. Clinical monitoring of thyroid function is also required to exclude or detect early signs of iodine-induced hyperthyroidism.

Adverse reactions.

Immune system: hypersensitivity, anaphylactic reactions.

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

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

Endocrine system: 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 decreased blood pressure and/or breathing difficulties (anaphylactic reactions) may occur.

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

Shelf life: 3 years.

Storage conditions:

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging:

30 ml, 120 ml, or 1000 ml of solution in a green plastic bottle with dropper; 1 bottle of 30 ml or 120 ml in a cardboard box; 1000 ml bottles are packed in shipping containers.

Category of supply: Over-the-counter (without prescription).

Manufacturer:

EGIS Pharmaceuticals Plc., Hungary.

Manufacturer's address and place of business:

65 Matyas Kiraly Street, Kermend, 9900, Hungary.