Ranostop®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RANOSTOP® (RANOSTOP)

Composition:

Active substance: povidone-iodine;

1 ml of solution contains 100 mg of povidone-iodine (equivalent to 10 mg/g of free active iodine);

Excipients: glycerol, citric acid monohydrate, disodium phosphate, poloxamer 338, purified water.

Pharmaceutical form. Solution for external and local use.

Main physicochemical properties: dark brown liquid.

Pharmacotherapeutic group. Antiseptics and disinfectants. Povidone-iodine.

ATC code D08AG02.

Pharmacological properties.

Pharmacodynamics.

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

Upon contact with the 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, and thus a change in the intensity of the brown color serves as an indicator of its effectiveness.

The active ingredient of the drug Ranostop® 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 (protozoicidal).

Due to the 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 the absorption of a significant amount of iodine. As a rule, prolonged use of the drug results in a rapid increase in blood iodine levels. 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 35,000–50,000, retention of the substance is possible.

The volume of distribution corresponds to approximately 38% of body weight. The biological half-life after vaginal administration is about 2 days. The normal total plasma iodine level is approximately 3.8–6 µg/dL, and the level of inorganic iodine is 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 of iodine per 1 g of creatinine).

Clinical characteristics.

Indications.

• Disinfection of hands and antiseptic treatment of mucous membranes, e.g., prior to surgical procedures, gynecological and obstetrical 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 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 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 at pH 2–7.

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, which may affect the results of certain diagnostic tests (e.g., thyroid scintigraphy, determination of protein-bound iodine, measurement of radioactive iodine), or may interact 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.

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

The medicinal product may react with proteins and unsaturated organic compounds; therefore, the effect of povidone-iodine may be counteracted, necessitating an increase in dosage.

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

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 medications. 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 thyroid dysfunction (e.g., nodular colloid goiter, endemic goiter). Therefore, in such patients, the duration of application and the skin surface area treated should be limited.

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 individual 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 application in large amounts over extensive areas (over 10% of body surface) in patients (especially elderly patients) with latent thyroid dysfunction should only be permitted after careful assessment of the expected benefit versus potential risk. Such patients should be monitored for early signs of hyperthyroidism and appropriate thyroid function tests should be performed, even after discontinuation of the drug (for up to 3 months).

When used in oropharyngeal applications, pneumonitis may occur.

Use during pregnancy or breastfeeding.

Povidone-iodine may be used only when prescribed by a physician and only in the smallest possible doses. Iodine crosses the placental barrier and may pass into breast milk; therefore, there is a risk of fetal or neonatal hypersensitivity to iodine. The concentration of povidone-iodine is higher in breast milk than in blood serum. Thus, the drug may cause hyperthyroidism or elevated thyroid hormone levels in the fetus or newborn. Monitoring of thyroid function in infants is required.

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 product is intended for topical use in both undiluted and diluted forms.

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

Dosing.

Undiluted Ranostop® solution is used for disinfection of hands and skin prior to surgical procedures, urinary catheterization, 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 specified 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:

Table 1.

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 they more frequently exhibit increased sensitivity to iodine, increasing the risk of developing 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;
• 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, renal function, and thyroid function.

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

Adverse Reactions.

Immune system disorders: hypersensitivity, anaphylactic reactions.

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

Skin and subcutaneous tissue disorders: local hypersensitivity skin reactions such as contact dermatitis with psoriasis-like red, small bullous formations; 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 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, mainly in patients with pre-existing thyroid disease.

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

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

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:

50 or 100 ml in polymer bottles, closed with dropper caps and sealed with polymer caps with a tamper-evident seal. One bottle per carton.

Dispensing category:

Over-the-counter (without prescription).

Manufacturer:

JSC "FITOPHARM".

Manufacturer's address and place of business:

84500, Bakhmut, Sibirtseva St., 2, Donetsk region, Ukraine.

Marketing Authorization Holder:

JSC "FITOPHARM".

Address of the Marketing Authorization Holder:

7, Verkhovnoi Rady Ave., office 18, 3rd floor, Kyiv, 02100, Ukraine.