Betadine Gargle

Povidone-iodine (as active iodine).

BETADINE GARGLE is black-brown transparent liquid with characteristic aroma.
BETADINE GARGLE is a liquid formulation for gargling containing povidone-iodine, which exerts disinfecting action by releasing iodine.
Each ml of BETADINE GARGLE contains 70 mg of povidone-iodine (7 mg as active iodine).
Povidone-iodine JP is a dark red-brown powder with a slight characteristic odor.
It is freely soluble in water or ethanol and practically insoluble in ether. pH of an aqueous solution (1-->100) of the substance is 1.5 to 3.5.
Chemical name: Poly[(2-oxo-1-pyrrolidinyl) ethylene] iodine.
Molecular formula: (C₆H₉NO)_n.xl.
Excipients/Inactive Ingredients: Eucalyptus Oil, Menthol, Methyl Salicylate, Glycerin, Saccharin Sodium, Disodium Hydrogen Phosphate. 12 H₂O, Citric Acid Monohydrate, Ethyl Alcohol and Purified Water.

Antiseptics. ATC code: R02AA15.
Pharmacology: Pharmacodynamics: Mechanism of action: Povidone-iodine is a complex of elemental iodine (I₂, the active moiety) and the synthetic polymer povidone, PVP, which acts as a sustained release reservoir of iodine (PVP does not have any intrinsic antibacterial activity) and also enables easier contact of iodine to cell membranes.
As povidone-iodine comes in contact with the skin and mucous membranes, iodine dissociates from the povidone-iodine polymer complex; it is the free iodine that rapidly causes microbicidal activity, whereas iodine bound to the polymer serves as an iodine reservoir. This gradual release of iodine reduces the drawbacks associated with the presence of elemental iodine and maintains its highly effective microbiocidal activity. The free iodine rapidly penetrates microorganisms and attacks the key groups of proteins, amino acids, nucleotides and unsaturated fatty acids. It reacts with thiol, sulfhydryl and hydroxyl groups of the amino acids in the enzymes and structural proteins of the microorganisms thereby oxidising them.
No development of resistance has been observed for povidone-iodine, during >60 years of intense use in hospitals, dental and medical. Furthermore, antibiotic resistance has no influence on the sensitivity to povidone-iodine. Because of this mechanism of action resistances, including secondary resistance upon prolonged use, are not to be expected.
Pharmacodynamic effects: Povidone-iodine has demonstrated an extensive anti-bacterial (gram positive and gram negative), anti-fungal and virucidal activity (enveloped and non-enveloped viruses).
Disinfection effect on bacteria: The disinfecting effect of BETADINE GARGLE on various bacterial species after 30-fold dilution with water is shown in the table as follows. (See Table 1.)

Click on icon to see table/diagram/image

To evaluate the effect of gargling with this product, experiment using bouillon were performed in 10 subjects with oral disease and 10 subjects without it. When mouth washing after BETADINE GARGLE from those subjects were incubated in thioglycollate bouillon at 37°C for 24 h, BETADINE GARGLE was found to have inhibitory effect on the bacterial growth.
Pharmacokinetics: The pharmacokinetics of povidone-iodine are influenced by the dissociation of povidone and iodine and its subsequent reduction to iodide in the body. Different formulations and different routes of administration would impact on the absorption of povidone-iodine and the extent of the systemic absorption of each formulation of povidone-iodine depends on the localisation and the conditions of its use (area, healthy skin surface, damaged skin surface, mucous membranes, wounds, body cavities).
Absorption: Studies in vivo indicate that the skin absorbs iodine and the amount absorbed is dependent on the type of skin (e.g. healthy or damaged) and also on the duration and the surface area of the application. Limited amount of iodine is absorbed through an intact skin; enhanced absorption occurs through denuded skin, ulcers, mucosal surfaces with high, absorptive capacity (vagina), or large areas of intact skin.
A negligible amount of povidone (~35 KDa) could be absorbed into the systemic circulation.
Following oromucosal administration, limited amount of iodine is absorbed through mucous membranes; if ingested, iodine is reduced to iodide in the gut, which is absorbed by the small intestine and in part incorporated into the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). A negligible amount of povidone (~35 KDa) could be absorbed into the systemic circulation.
Distribution: Independently from the route of administration, absorbed iodine/iodide is distributed throughout the body via the circulatory system. A portion (approximately 30%) is removed by the thyroid for hormonal synthesis. Iodine is also distributed (despite to a minor extent) to different organs including liver, blood and thyroid gland after 24 hours. Iodine crosses the placenta and is excreted in breast milk.
Povidone is negligibly absorbed following topical, oral or vaginal application. Povidone does not pass the blood brain barrier or cross the placenta.
Metabolism: Iodine is reduced to iodide and is concentrated from the blood stream into the thyroid follicular cell through the action of the sodium/iodide symporter (NIS). The thyroid-stimulating hormone (TSH) stimulates iodide transport from the blood into thyroid cells, oxidation of iodide to iodine, and iodine binding to tyrosine. The metabolism of povidone is minimal (<0.3%).
Excretion: Iodine, unless utilised in the thyroid, is excreted mainly via urine. The renal clearance of iodine (Cl) is found to be 872.4±119.3 mL/h with constant elimination rate (k) 0.0996±0.009/hour and a half life of 6.22 hours. The excretion of povidone is mainly via urine and in a small amount also via bile.
Toxicology: Preclinical Safety Data: The oral LD₅₀ for mice, rats and guinea pigs is 40-100 g/kg and the intraperitoneal LD₅₀ for mice is 12-15 g/kg (povidone average molecular weight 10-30 KDa).
Acute, subchronic and chronic toxicity studies with povidone-iodine show toxicity, following systemic administration, at relatively high doses and as such the toxicity is not considered relevant to clinical use.
Genotoxicity: Several in vitro genetic toxicology studies suggest that povidone-iodine may be mutagenic, while other studies have shown negative findings, including separate in vivo studies. Taking into account the toxicity of PVP-I to the in vitro test systems, the weight of evidence suggests that PVP-I is not genotoxic. No long-term studies in animals have been conducted to evaluate the carcinogenic potential of povidone-iodine.
Reproductive and developmental toxicity: Developmental toxicity studies in the rabbit indicate that a low molecular weight povidone-iodine complex (16-75 mg/kg/day) caused a dose dependent decrease in body weight gain in the mother and the average embryo and placenta weights were lower than those of the control animals. Embryotoxicity has been demonstrated when PVP-I is applied to the vaginal opening in the mouse. Due to the ability of iodine to pass through the placenta and the sensitivity of the foetus to pharmacological doses of iodine, povidone-iodine should only be used in pregnant women after careful medical evaluation.

Pharyngitis, tonsillitis, stomatitis, gum inflammation. Disinfection of the oral cavity to prevent bad breath. Prevention of oral wound infections including one after tooth extraction and surgery in oral cavity.

Dilute the product 15- to 30-fold (dilute 1-2 ml with about 30 ml of water) on use, and gargle several times a day.
1. Drop BETADINE GARGLE 1-2 cc. into the mixing cup.
2. Mix with 30 cc. of water.
3. Gargle for 30 seconds.
4. The mixing cup can be put back on the top of the bottle for further reuses.
In the case of an oral wound due to, for instance, tooth extraction, avoid vigorous mouth washing with this product at the time when formation of blood clots may be inhibited.

Acute iodine toxicity is manifested by abdominal symptoms, anuria, circulatory collapse, pulmonary edema and metabolic abnormalities.
Systemic toxicity may result in renal impairment (including anuria), tachycardia, hypotension, circulatory failure, oedema of glottis resulting in asphyxia, or pulmonary oedema, seizures, fever and metabolic acidosis. Hyperthyroidism or hypothyroidism may also develop.
Treatment is symptomatic and supportive.
For severe hypotension, intravenous fluid should be administered; vasopressors should be added if necessary.
Endotracheal intubation may be required if caustic injury to the upper airway results in significant swelling and oedema.
Vomiting should not be induced. Patient should be maintained in a position to keep the airways open and prevent aspiration (in case of vomiting).
If the patient is not vomiting and can tolerate oral feeding, then ingestion of starchy food (e.g. potato, flour, starch, bread) may help convert iodine to less toxic iodide. If no signs of bowel perforation are present, irrigation of the stomach with starch solution via nasogastric tube may be utilized (gastric effluent will turn dark blue-purple and the colour can be used as a guide in determining when lavage can be terminated).
Haemodialysis effectively clears iodine and should be employed in severe cases of iodine poisoning particularly if renal failure is present. Continuous venovenous haemodiafiltration is less effective than haemodialysis.
In case of thyroid dysfunction, treatment with povidone-iodine should be discontinued.

Contraindicated in: Hypersensitivity to the active substance(s) or to any of the excipients (see Description).
Thyroid dysfunction.
Duhring's dermatitis herpetiformis.
Before, during and after radioiodine administration (see Interactions).
Products containing mercury, should not be used concomitantly due to formation of a substance which can damage the skin.
Children below the age of 1.

In oropharyngeal use precautions should be taken to prevent aspiration of BETADINE GARGLE into the respiratory tract as this may cause complications such as pneumonitis. This may particularly occur in intubated patients.
Special caution is needed in pregnant and breast-feeding patients. In such cases benefit/risk assessment should be performed and povidone-iodine should only be administered if clearly necessary (see Use in Pregnancy & Lactation).
Effect on Ability to Drive and Use Machines: BETADINE GARGLE has no influence on the ability to drive and use machines.

Povidone Iodine passes into the placenta and is secreted in breast milk. Thyroid function disorders including congenital hypothyroidism have been reported in the offspring of mothers who have received Iodine.
Povidone Iodine use should be avoided unless the potential benefit to the mother justifies the potential risk to the foetus and neonate or if a safer alternative is unavailable.
Fertility: There are limited human fertility data for Povidone iodine. No data are available on fertility outcomes.

The following frequencies are the basis for assessing undesirable effects: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data). (See Table 2.)

Click on icon to see table/diagram/image

The Povidone-iodine complex is effective at pH values of between 2.0 and 7.0. It has to be expected that the complex will react with protein and other unsaturated organic compounds, leading to impairment of its effectiveness.
The concomitant use of wound-treatment preparations containing enzymatic components leads to a weakening of the effects of both substances. Products containing mercury (see Contraindications), silver, hydrogen peroxide, and taurolidine may interact with povidone-iodine and cause mutual reduction of effects.
Povidone-iodine products when used before or after application of octenidine may lead to transient dark discolourations at the application site.
Due to the oxidative effect of povidone-iodine preparations various diagnostic agents can show false-positive lab results (e.g., tests with toluidine or gum guaiac for the determination of hemoglobin or glucose in the stool or the urine).
Absorption of iodine from povidone-iodine products may lower the iodine uptake of the thyroid. This can lead to interference with various investigations [(thyroid scintigraphy, determination of protein-bound iodine (PBI), radioiodine diagnostics)] and can make a planned treatment of the thyroid with iodine (radioiodine therapy) impossible. After the end of the treatment, 4 weeks should be allowed before anew scintigram is carried out (see Contraindications).

Incompatibilities: Povidone-iodine should not be used together with alkali, hydrogen peroxide, taurolidine, tannic acid, and silver and mercury salts.
Avoid contact with jewelry, especially silver containing articles.
Caution for Handling: Caution: Dilute the product on use and use it immediately.
Other: The product can be easily washed off with water and decolorized by sodium thiosulfate solution if it contacts clothes.

Store below 30°C protecting from direct sunlight.

Preparations for Oral Ulceration & Inflammation

R02AA15 - povidone-iodine ; Belongs to the class of antiseptics used in throat preparations.

NDD