BETADINE ALCOOLIQUE 5 % S appl cut Fl PEHD/125ml

Solution for cutaneous application.
Bottle containing 125 ml of solution.
Bottle containing 125 ml or 500 ml of solution (hospital models).

For 100 ml:

Povidone iodine: 5,00 g
Ethanol at 96 %: 72,00 ml

• Antisepsis of healthy skin before minor surgical procedures or before certain invasive procedures such as punctures and injections. The official therapeutic recommendations in force should be respected.
• Surgical antisepsis: preparation of the operative field.

Note: Antiseptic agents are not sterilising. They temporarily reduce the number of microorganisms.

Dosage

Cutaneous use.

Approximately 5 ml of product should be applied to the skin surface with a sterile compress for at least 10 seconds and allowed to dry for approximately 30 seconds before the minor surgical procedure or before certain invasive procedures such as punctures and injections.

Surgical antisepsis: preparation of the operative field:

• Cutaneous cleansing with a foaming solution for cutaneous application based on povidone iodine.
• Rinsing with 10 ml of physiological saline.
• Drying with a sterile compress.
• Cutaneous antisepsis in 2 successive applications of one minute each BETADINE ALCOHOLIC 5 % separated by a spontaneous air-drying time of one minute.

This medicine MUST NOT BE USED in the following situations:

• History of hypersensitivity to one of the constituents, in particular povidone. There are no cross-reactions 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 ALCOHOLIC 5 %.
• 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).

Special warnings

Due to transcutaneous absorption of iodine, repeated or prolonged treatment may expose to a risk of systemic effects, in particular thyroid dysfunction (see section Adverse effects).

These systemic effects, favoured by repeated applications, are all the more to be feared when the antiseptic is used over a large surface, under an occlusive dressing, on damaged skin (in particular burned skin), a mucous membrane, or the skin of a premature infant or infant (due to the surface-to-weight ratio and the occlusive effect of nappies in the diaper area).

Special attention is required during repeated applications on damaged skin in patients with renal insufficiency.

BETADINE ALCOHOLIC 5 % must not be used in severely burned patients (see section Adverse effects).

Contraindicated in children under 12 months; use in children under 30 months, if deemed essential, should be limited to a brief application over a small area and must be followed by rinsing with sterile water.

Do not use near a heat source or flame due to the risk of flammability associated with the presence of alcohol.

Cases of burns have been reported when using electrosurgical units after application of BETADINE ALCOHOLIC 5 %, related to residual product. It is therefore necessary to ensure, after preparing the operative field, that the product is completely dry and that there are no residual amounts of product that could have run, particularly into skin folds, or onto the table drape.

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.

Precautions for use

To be used with caution under all conditions likely to promote systemic absorption, and particularly in children under 30 months of age (see section Contraindications).

When preparing the patient for surgery, avoid runoff and pooling between the patient and the table drape. 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.

Given possible interferences (antagonism, inactivation), concurrent or sequential 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.

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 occurs during the 2^th trimester, but at the end of pregnancy it may give rise to goiter.

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 2th trimester.

Its use on an occasional 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).

**** May occur in case of maceration under the patient preoperatively.

˄ Due to the risk of flammability, the alcoholic povidone-iodine solution must dry completely before using surgical equipment (in particular electrosurgical scalpel).

˄˄ May occur after repeated use due to the presence of alcohol in the solution; the risk is greater in the genital area (in particular the scrotum).

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.

Treatment, to be carried out in a specialised setting, is symptomatic and adapted as needed.

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: Antiseptics and disinfectants, ATC code: D08AG02.

Broad-spectrum bactericidal, fungicidal, virucidal antiseptic.

Belongs to both the class of iodine derivatives and the class of alcohols.

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

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

Iodophors are unstable at alkaline pH.

Skin coated with povidone-iodine takes on a brown coloration that is easily removed with water.

Efficacy in surgical antisepsis of the operative field:

Microbiological efficacy was measured at sampling times 2 min, 1 h and 3 h after the second application of BETADINE ALCOHOLIC according to the protocol. This study showed a still substantial decrease in the number of germs present on the skin at 3 hours.

The available iodine of povidone-iodine can cross the skin barrier.

Its elimination will occur mainly via the urinary route.

Povidone alone can in no case give rise to systemic passage.

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.

The iodine/mercurials combination is to be avoided, risk of formation of caustic compounds.

Iodine is an oxidant (chemical incompatibilities with reducing agents).

Iodine is inactivated by sodium thiosulfate (possible antidote).

The product is unstable to heat, light and alkaline pH.

3 years.

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

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

No special requirements.