1. NAME OF MEDICINAL PRODUCT
Kalii iodidum Ramcopharm, 65.0 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:
Active ingredient: Potassium iodide, 65 mg (equivalent to 50 mg of iodine).
For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM
Tablets

4. CLINICAL PARTICULARS

4.1. Therapeutic indications
Used to block or reduce the accumulation of radioactive isotopes of iodine in the thyroid gland and consequently to reduce the risk of hypothyroidism and thyroid cancer in accidents involving radioactive contamination and release of iodine and technetium radionuclides (accidents at nuclear power stations, terrorist acts etc.)

4.2. Posology and method of administration

  • Adults and children over 18 years: two 65 mg tablets of Kalii iodidum once a day.
  • Pregnant and nursing women: two 65 mg tablets of Kalii iodidum. It is recommended that pregnant or nursing women take only a single dose of Kalii iodidum and be immediately taken away to a safe uncontaminated place.
  • Children from 3 to 18 years of age: one 65 mg tablet of Kalii iodidum. Adolescents whose body weight is 70 kg or more should take the adult dose.
  • Infants/toddlers from 1 month to 3 years: ½ 65 mg tablet of Kalii iodidum.
  • Nursing newborns (up to 1 month): ¼ 65 mg tablet of Kalii iodidum.

The recommended doses summarised above should be administered as soon as possible after an accident and supposed exposure (within 3 hours of the accident). One dose should be taken every 24 hours while there is a risk of exposure (by inhalation or ingestion of contaminated food and drink). Newborns (under 1 month), pregnant and nursing women are advised to take only a single dose (See 4.4. Special warnings and precautions). Tablets should be administered after meals and may be swallowed whole with plenty of liquid or crushed and mixed in drinks or milk.

4.3. Contraindications
The medicinal product is contraindicated in patients with:

  • an active thyroid disease or a history of such diseases
  • known hypersensitivity to iodine
  • dermatitis herpetiformis
  • hypocomplementaemic vasculitis.

4.4. Special warnings and precautions

  • To ensure maximum efficacy, Kalii iodidum must be taken immediately after or just before exposure. Potassium iodide does not provide protection against the immediate effects of ionising radiation and does not inhibit the absorption of ionising radiation by the body. Prevention using this medicinal product does not eliminate the need for immediate evacuation, especially for nursing infants, young children, pregnant and nursing women, from areas near the accident and does not preclude the need for shelter and supply of uncontaminated food, water, etc. A single dose of potassium iodide provides effective protection against the accumulation of radioactive iodine isotopes for about 24 hours, but when evacuation or provision of uncontaminated food is impossible the medicinal product should be taken daily during exposure; however, it is advisable that the period of Kalii iodidum administration does not exceed 10 days.
  • Nursing newborns aged up to 1 month are particularly sensitive to the immediate and delayed effects of radioactive iodine isotopes on the thyroid gland. At the same time, they are at the greatest risk of the adverse effects of potassium iodide (hypothyroidism). For this reason, it is advised to administer a single dose of Kalii iodidum to nursing newborns (aged less than one month), which provides protection to the thyroid gland against accumulation of radioactive iodine isotopes for 24 h, and to also provide them with uncontaminated food and ensure their immediate evacuation. It is advisable to avoid prolonged administration of this medicinal product in this group of patients. In cases where Kalii iodidum is used for prevention, nursing newborns under the age of 1 month should be monitored closely for signs of hypothyroidism.
  • In children and adolescents (from 1 month to 18 years) there is a high risk of thyroid gland damage from radioactive iodine isotopes, but the risk of side effects of Kalii iodidum is relatively low. Therefore, in cases where the exposure (by inhalation or ingestion of contaminated milk or food) is prolonged, the recommended dose should be taken daily. It is advisable that the duration of intake should not exceed 10 days.
  • Adult patients, including pregnant and nursing women, should avoid taking more than one dose of Kalii iodidum, except in cases where there is prolonged exposure (by inhalation or ingestion of contaminated food). Intake of potassium iodide by pregnant and nursing women may lead to rashes or hypothyroidism in the newborn/nursing infant. It is advisable to monitor the function of the thyroid gland in the newborn/nursing infant, especially in cases where the mother has taken several doses of potassium iodide. Nursing women are advised to temporarily stop breastfeeding for the period during which they are taking potassium iodide (usually 1-2 days), until evacuation to a safe area.
  • In people aged over 40 years the risk of thyroid cancer after radiation exposure is extremely low, while the risk of side effects of potassium iodide increases with age. In these patients, prevention using potassium iodide is indicated only at doses of ionising radiation of the order of 5 cGy, which may realistically be expected only in patients located in areas close to the accident.
  • The risk of adverse reactions to Kalii iodidum (especially hyperkalemia) increases in patients with kidney diseases, and therefore the condition of such patients should be monitored carefully.
  • The medicinal product should be used with caution in patients with congenital myotonia and hyperkalemia, whose potassium levels should be carefully monitored.
  • In patients with tuberculosis Kalii iodidum should be used with caution because of the risk of significantly enhancing the expectoration.

4.5. Interaction with other medicinal products and other forms of interaction

Concomitant use of potassium-sparing diuretics, ACE inhibitors and other potassium-containing medicinal products or food supplements increases the risk of hyperkalemia and related effects on cardiac function. Taking Kalii iodidum with lithium salts or thyreostatics can enhance hypothyroid and strumigenic effects of these drugs. Concomitant use of Kalii iodidum and iodophores such as amiodarone, clioquinol and diagnostic contrast agents increases the risk of damage to the function of the thyroid gland. The use of iodine-containing antiseptics for treatment of large skin surfaces combined with oral administration of potassium iodide should be avoided, especially at nursing age because of the risk of systemic resorption and increase in the adverse effects on the thyroid gland.

4.6. Pregnancy and lactation

Administration of Kalii iodidum during pregnancy is imperative, given the risk of accumulation of radioactive iodine isotopes in the thyroid of the foetus. It is recommended that pregnant and lactating women receive two 65 mg tablets as a single dose and immediately be taken away from the site of exposure. Kalii iodidum should be taken again only in case of unavoidable long-term exposure. It is advisable that newborns should be monitored closely for signs of inhibition of thyroid function and/or struma.

Due to the risk of overdose and for the purpose of more accurate dosing for the nursing infant, discontinuation of breastfeeding is recommended (for 1-2 days) when nursing women are taking potassium iodide.

Iodine is excreted in breast milk, with the possibility to eliminate up to ¼ of the amount taken by the mother from the breast milk in 24 hours. It is advisable to administer only a single dose of this medicinal product to lactating women (except in cases of prolonged exposure). In cases where more than one tablet of the medicinal product is needed, the nursing infants should be monitored closely for signs of iodism, inhibition of thyroid function or rashes.

4.7. Effects on ability to drive and use machines
None known.

4.8. Adverse reactions
The following may occur: hypersalivation, metallic taste in the mouth, lacrimation, painful teeth and gums, irritation of the stomach lining, headache, swelling of the salivary glands and diarrhoea. Serious allergic reactions such as angioedema, arthralgia, eosinophilia and swollen lymph nodes are very rare and require careful monitoring and discontinuation of the medicinal product’s administration. Iodism events (burning sensation in the oral cavity and throat, irritation of the stomach, copious watery salivation, severe headache and acne-like rashes and other skin lesions) and potassium toxicity (confusion, stiffness, numbness or weakness of the hands and/or legs, fatigue, cardiac arrhythmias) are observed when this medicine is administered over a long period. The risk of inhibition of thyroid function from a single dose is negligible, but in cases of prolonged exposure involving the administration of potassium iodide over a few days, symptoms of hypothyroidism may occur, especially in newborns and elderly patients.

4.9. Overdose
Early symptoms following an overdose of potassium iodide include stimulating exocrine glands with rhinorrhea, conjunctivitis and cough with discharge of serous exudates. Consequently, the following may occur: metabolic acidosis, hyperosmolarity, hypernatremia, hyperkalemia, acute respiratory distress, congestive heart failure, kidney failure, coma and death. There is no specific antidote.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties ATC : V03AB21-Antidotes
Potassium iodide accumulates selectively in the thyroid and saturates transport proteins providing transport of iodine in the gland, thereby preventing the accumulation of radioactive iodine isotopes (131I, 132I, 133I, 135I) and technetium. Thus, it provides protection of the thyroid gland from the immediate and delayed effects of ionising radiation emitted by radionuclides. Taking Kalii iodidum at the time of or immediately before exposure to iodine radionuclides blocks 97% of the radioactive iodine that could accumulate in the gland. If Kalii iodidum is taken 12 hours before potential exposure, it again provides a protective effect of about 90% against the absorption of radioactive iodine by the thyroid gland. If potassium iodide is taken 24 h before the exposure, it blocks about 70% of the potential accumulation of 131I. The administration of this medicinal product 4-6 hours after contact with iodine radionuclides blocks their accumulation in the thyroid by only about 50%, while taking potassium iodide after 8 h has virtually no protective effect.

5.2. Pharmacokinetic properties
Kalii iodidum is absorbed rapidly and completely in the gastrointestinal tract, within 30-60 minutes of oral administration. Iodide anions are concentrated in the thyroid, where thyroid peroxidase turns them into molecular iodine, which is used to synthesise thyroid hormones; selective accumulation of iodides also occurs in the salivary glands, mammary glands and kidneys. Iodide ions unabsorbed by the thyroid are removed unchanged through urine by means of glomerular filtration and to a lesser extent through faeces.

5.3. Preclinical safety data
According to the Hodge & Sterner Scale, potassium iodide administered orally is less toxic, with LD50 from 500 to 5000 mg/kg. In subchronic toxicity experiments on rats, it was found that young animals are more susceptible to the toxic effects of potassium iodide than adult animals. At low doses, potassium iodide is not teratogenic, carcinogenic, embryo- and foetotoxic.

6. PHARMACEUTICAL PARTICULARS

 6.1. List of excipients:
Each tablet contains the following excipients:

Cellulose, microcrystalline                             – Ph. Eur. V                0.0725 g
Sodium hydrogen carbonate                         – Ph. Eur. V                0.0100 g
Silica, colloidal anhydrous                            – Ph. Eur. V                0.0015 g
Magnesium stearate                                       – Ph. Eur. V                0.0010 mg

6.2. Incompatibilities
None known.

6.3. Shelf-life
5 years

6.4. Special precautions for storage
Store in original container in a dry and dark place at temperatures below 25°C. Keep out of reach of children.

6.5. Nature and contents of container
PVC / aluminium foil blister packs of 10 tablets.
1 blister pack in a cardboard box with instructions for use.

7. MANUFACTURER AND MARKETING AUTHORISATION HOLDER:
Ramcopharm OOD, 5A Plachkovitsa Str., 1164 Sofia

8. MARKETING AUTHORISATION NUMBER – II-10982 / 17 June 2005

9. DATE OF LAST REVISION:
NOVEMBER 2010