BETADINE 10 % S vag Fl/125ml

Vaginal solution.
Bottle of 125 ml.
Bottle of 500 ml (hospital model).

For 100 ml:

Povidone iodine (titrated to 10 % iodine): 10 g

Adjunctive local treatment of vaginal infections caused by susceptible organisms and vulvo-vaginal preparation prior to an invasive medical procedure or surgery of the urogenital area.

Diluted use with a vaginal irrigation kit:

1 or 2 daily vaginal irrigations at the dilution of two tablespoons per litre of lukewarm water.

Undiluted use:

Internal or external swabbing.

This medicine MUST NOT BE USED in the following situations:

• History of hypersensitivity to any of the constituents, in particular povidone. There is no cross-reactivity with iodinated contrast media. Intolerance reactions (anaphylactoid reactions) to iodinated contrast media or anaphylaxis to seafood do not constitute a contraindication to the use of BETADINE 10 %, vaginal solution.
• Child aged less than 1 year.
• Prolonged use during the 2^th and the 3^th trimester of pregnancy.
• Breastfeeding is contraindicated in case of prolonged treatment.
• Hyperthyroidism and other acute thyroid diseases.
• Before, during and after administration of radioactive iodine (see section Interactions)
• Use with products containing mercury (see section Interactions)

Due to possible resorption of iodine through mucous membranes, repeated or prolonged treatment may expose patients to a risk of systemic effects, in particular thyroid dysfunction (see section Adverse effects). These systemic effects are favoured by repeated applications and in cases of renal insufficiency.

Avoid prolonged or repeated use.

Avoid dripping. Prolonged contact with the undried solution may cause irritation and, rarely, severe skin reactions such as burns. In case of skin irritation, contact dermatitis or hypersensitivity, discontinue use. Do not heat before application.

This medicine is not recommended in combination with spermicidal products.

As soon as the packaging of an antiseptic preparation is opened, microbial contamination is possible.

The volume of bottles larger than 250 ml exposes the solution to a risk of contamination if it is used for a prolonged period after opening.

Gynaecological antiseptics may inactivate local spermicides and hinder their contraceptive activity.

Given the possible interactions (antagonism, inactivation), concomitant or successive use of antiseptics should be avoided.

Products containing mercury may react with povidone-iodine to form mercury iodide, which is highly corrosive.

Povidone-iodine may reduce iodine uptake by the thyroid. Therefore, the use of povidone-iodine may interfere with thyroid tests (scintigraphy, determination of protein-bound iodine, diagnostic tests with radioactive iodine) and make radioactive iodine treatment impossible. It is advised to wait 4 weeks after application of povidone-iodine before performing an examination or treatment with radioactive iodine.

Combinations not recommended

+ Spermicides and medicines used by the vaginal route (antifungals, antitrichomonal agents, antibacterials, antiseptics, antiherpetic agents and local oestrogens).

Any local vaginal treatment may inactivate local spermicidal contraception.

Pregnancy

Animal studies have not shown any teratogenic effect. In the absence of a teratogenic effect in animals, a malformative effect in humans is not expected. Indeed, to date, substances responsible for malformations in humans have been shown to be teratogenic in animals in well-conducted studies in two species.

Clinically, there is currently no sufficiently relevant data to assess a possible malformative effect of povidone-iodine when administered in the first trimester of pregnancy.

The fetal thyroid begins to fix iodine after 14 weeks of amenorrhea; no effect on the fetal thyroid is expected in case of prior administrations.

Iodine overload, very likely with prolonged use of this product beyond this period, may lead to fetal hypothyroidism, biological or even clinical (goiter).

This is reversible if administration takes place during the 2^th trimester, but at the end of pregnancy, it may give rise to goitre.

Consequently, as a precautionary measure, it is preferable not to use this medicine during the 1^er trimester of pregnancy.

In case of use prolonged, its use is contraindicated from the 2^th trimester.

Its use on a one-off basis should only be considered if necessary.

Breast-feeding

Iodine passes into breast milk at concentrations higher than in maternal plasma. Due to the risk of hypothyroidism in the infant, breastfeeding is contraindicated during treatment prolonged with this medicine.

Fertility

Current data on the fertility effects of povidone-iodine are limited.

Frequencies of undesirable effects have been classified as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1 000, < 1/100), rare (≥ 1/10 000, < 1/1 000), very rare (< 1/10 000), frequency not known (cannot be estimated from available data).

* In patients with a history of thyroid pathology (see section Warnings and precautions), following significant iodine absorption, for example in cases of repeated use for the treatment of wounds or burns over extensive surfaces.

** Hypothyroidism following prolonged or extensive use of povidone-iodine.

*** May occur through absorption of large volumes of povidone-iodine following exposure of large skin or mucous membrane surfaces (e.g. treatment of burns).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.

Overdose is not expected under normal conditions of use.

Massive accidental ingestion or absorption of large volumes of povidone-iodine following exposure of large skin or mucous membrane surfaces (healthy or damaged) may lead to severe systemic iodine intoxication. Systemic iodine intoxication may cause abdominal pain, vomiting and bloody diarrhoea, tachycardia, hypotension, circulatory failure, glottic oedema leading to asphyxia, pulmonary oedema, aspiration pneumonia, convulsions, fever, metabolic acidosis, hypernatraemia and/or renal failure (including anuria). Hyperthyroidism or hypothyroidism may also develop.

The treatment, to be carried out in a specialised setting, is symptomatic and adapted according to needs.

In cases of severe hypotension, an intravenous solution must be administered; vasopressors must be added if necessary.

Endotracheal intubation may be necessary if the caustic injury to the upper airways causes significant swelling and oedema.

Vomiting must not be induced. The patient must be kept in a position that keeps the airways clear and prevents aspiration (in case of vomiting).

If the patient is not vomiting and can tolerate oral feeding, ingestion of starch-rich foods (for example potato, flour, starch, bread) may help convert iodine into the less toxic iodide. In the absence of signs of intestinal perforation, gastric irrigation with a starch solution via nasogastric tube may be used (the gastric effluent turns dark blue-violet and the colour can be used as a guide to determine the end of the lavage).

Haemodialysis effectively eliminates iodine and should be used in severe cases of iodine intoxication, particularly in cases of renal failure. Continuous veno-venous haemofiltration is less effective than haemodialysis.

In case of thyroid dysfunction, treatment with povidone-iodine must be discontinued.

Pharmacotherapeutic class: IODINE ANTISEPTIC, ATC code: G01AX11 (G01A: Genito-urinary system).

Broad-spectrum bactericidal, fungicidal antiseptic.

The virucidal activity (including against H.I.V.) of BETADINE 10 %, vaginal solution has been established in vitro but not in vivo.

Povidone iodine is an iodophor product, an organic complex with approximately 10 percent active available iodine.

Organic matter (proteins, serum, blood...) decreases the activity of free iodine, the active form of this specialty.

Iodophors are unstable at alkaline pH.

The available iodine of povidone iodine may result in transmucosal passage.

Iodine crosses the placental barrier.

Its elimination will occur mainly via the urinary route.

Acute toxicity

In acute toxicity studies in mice, rats, rabbits and dogs, after systemic administration (oral, i.p., i.v.), toxic effects were observed only with excessively high doses that have no significance for local use of a povidone-iodine solution.

Thus the LD50 in rodents is greater than 200 mg/kg of available iodine (equivalent to 20 mL per kg of a pure 10% PVP-I solution) and by the intraperitoneal route, greater than 30 mg of available iodine per kg (equivalent to 3 mL per kg of an undiluted 10% PVP-I solution).

Chronic toxicity

Subchronic and chronic toxicity studies were conducted in rats, administering povidone-iodine (10% available iodine) in the diet at doses between 75 and 750 mg of povidone-iodine per day per kg of body weight for up to 12 weeks. After cessation of povidone-iodine administration, dose-dependent and reversible increases in serum protein-bound iodine and non-specific histopathological changes of the thyroid gland were observed. Similar changes also occurred in the control group that received potassium iodide in an iodine-equivalent amount instead of povidone-iodine.

In chronic IP treatment in rats starting from a dose of 5 mg/kg of PVP-I, severe peritonitis with adhesion of intra-abdominal organs is observed, which may lead to death of the animal.

Mutagenic and carcinogenic potential

PVP-I has no mutagenic potential.

No carcinogenicity study has been conducted.

Reproductive and developmental toxicity

A reproductive toxicity study was conducted in rabbits. Doses of 16, 35 and 75 mg/kg of body weight per day were administered intramuscularly to pregnant female rabbits for 12 days from the 6^th to the 18^th day of gestation. PVP-I was not teratogenic.

Animal fertility studies have not been conducted.

Iodophors are unstable at alkaline pH.

Povidone iodine is inactivated by sodium thiosulfate (possible antidote).

3 years.

After first opening of the vial, this medicine must be stored for a maximum of 6 months at room temperature.

Before opening: no special storage precautions.

For storage conditions after first opening, see section Shelf life.

No special requirements.