Summary of Product Characteristics

1. NAME OF THE MEDICAL PRODUCT

I-131-Sodium iodide injection for therapeutic purposes (I-RA-7)

I-131-Sodium iodide containing sterile injection for intravenous application. Contains no added iodide carrier.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

3. PHARMACEUTICAL FORM

Sterile, radioactive injection

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

This medical product is for RADIONUCLIDE THERAPY of the following diseases

a) Hyperthyreosis:

Radionuclide therapy of the hyperfunction, decrease of the size of the thyroid.

– Treatment of Basedow disease
– Treatment of hyperfunction adenomas
– Treatment of non-immunogen, diffuse goitre

b) Thyroid carcinoma:

Radionuclide therapy treatment

– Destruction of the remaining thyroid tissues after the operation of the thyroid (ablatio)
– Treatment of recidives and metastases

4.2 Posology and mode of administration

a) Treatment of hyperthyreosis

The administerable activity is to be calculated from the recommended absorbed dose with the following formula. On the other hand an activity originating from and determined by other recommendations may also be administered.

Recommended absorbed dose values:
– For treatment of Basedow disease: 40-80 Gy
– For treatment of hyperfunction adenoma: 300-400 Gy
– For treatment of non-immunogen, diffuse goitre: 150-200 Gy

Activity to be administered: A (MBq)

A (MBq) = [25 × M (g) × D (Gy) ] / [ F_max (%) × T_eff (day) ]

where M is the mass of the thyroid in grams, which is to be calculated from the scintigram by the planimetry method:

Activity values applied for treatment of hyperthyreosis usually fall in the range of 50 MBq – 1 GBq.

b) Treatment of thyroid tumour:

Mode of administration:

The general mode of administration is intravenous injection. In case of small activity per os (oral) administration is permitted, too.

4.3 Contraindications

RELATIVE CONTRAINDICATIONS

The use of the product is relatively contraindicated

– at the age below 18 years

except when the necessity and importance of the treatment prevails the risk originating from the radiation exposure.

ABSOLUTE CONTRAINDICATIONS

The use of the product is absolutely contraindicated

– in case of pregnant or lactating women,
– if the patient does not provide an oral or written consent of being treated by radionuclide therapy.

4.4 Special warnings and special precautions for use

The product is a radioisotope containing pharmaceutical. The rules for handling, transportation and storage of radioactive materials are applicable for the product.

The pharmaceutical can only be applied by properly qualified and trained personnel within designated clinical settings, which possess the appropriate government authorisation for the use and manipulation of radioisotopes.

The treatment of hyperthyreosis can be carried out in ambulant way as well. Such in case the relevant international and national prescriptions and regulations should be taken into consideration concerning the patient’s way of living are to be kept (mode of traffic, urination, living with family members, etc.).

The radionuclide therapy treatment of thyroid tumor can only be carried out in a designated health institute (hospital, clinic) with taking consideration of the relevant regulations.

4.5 Interactions with other medicinal products and other forms of interaction

Hindered I-131 uptake is disadvantageous both in case of thyroid scintigraphy and thyroid radionuclide therapy, therefore, introduction of inactive iodine is to be avoided. Such treatments are to be terminated prior to the administration of radioiodide according to the following table:

The clearance of radioiodide from the thyroid – in case of necessity – can be slowed down with lithium-carbonate. Colchicin also reduces the radioiodide clearance rate.

4.6 Application during pregnancy and lactation

Application of the product during pregnancy and lactation is contraindicated.

4.7 Effect of the product on ability to drive and on working in circumstances of significant accident risk

The product has no direct influence on ability of car driving or working in hazardous circumstances. In occurrence of unexpected side effects the ability to drive and the aptitude to work amidst accident risk are to be reconsidered.

4.8 Undesirable effects

Occurrence of undesirable effects and symptoms is unexpected.

4.9 Overdose

There is no information available about any actually occurred overdose.
Administration of higher activity than prescribed results in unnecessary absorbed radiation dose on the patient and her/his environment, which is to be avoided.

Administration of higher activity than necessary may cause hypothyreosis.
In occurrence of an eventual overdose the effective absorbed radiation dose is to be calculated with using the dosimetry table of the section 5.4 and the decision about the necessity and mode of further treatments are to be made based on the result.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Iodine is a microelement of vital importance, which is inevitably necessary to the synthesis of the metabolism regulating thyroid hormones.

90% of I-131-sodium-iodide introduced into the body gets to the blood within an hour and 100% of it within 4 hours. From the circulation system it runs to the thyroid, appears in the salivary glands, the placenta and it is excreted by the plexus chorioideus and the mucous membrane of the stomach. In case of lactating women it appears in the milk as well.

In normal case the body takes up approximately 100-500 µg iodine per day with the food, the optimum quantity is 150-300 µg per day (1). Adults’ minimum daily requirement is 100 µg (2). Approximately 10-60% (mostly 20-30%) of the introduced iodine quantity concentrates in the adults’ thyroid of 20 g weight in average, where it is built in the thyroid hormones and their precursors. The iodine concentration of the thyroid depends upon how extensively the satisfaction of the iodine demand is supported by the iodination of the foodstuffs. In Hungary 414 ± 280 µg/g thyroid value is common (3).

The specific activity of I-131 is at least 1 GBq/µg, therefore, even in case of administering the maximum recommended therapy dose (7.4 GBq) only 7.4 µg is introduced into the body. Comparing this value to the normal iodine intake data it is obvious that the therapy is not carried out by the pharmacokinetic effect of the chemical iodine quantity but it is the consequence of the energy and transmitted to the tissue during the absorption of the beta-particles emitted by I-131 nuclide, which is devoted to the destruction of the thyroid cells.

In normal case radioiodine washes out from the body with the urine.

5.2 Pharmacokinetic properties

90% of I-131-sodium-iodide introduced into the body per os gets to the bloodstream within an hour and 100% of it within 4 hours.

The kinetics of the radioiodine uptake in the thyroid highly depends on the degree of the iodine supply of the area where the patient lives. For the normal case:

In places of medium degree of iodine supply 20 ± 9% of the activity appears in the thyroid 2 hours after administration. After 6 hours 32 ± 12% is taken up, while the maximum activity (43 ± 11%) after 24 hours. Only 40 ± 10% is the uptake 48 hours subsequent to the administration.

In case of patients with iodine deficiency the uptake is extensive and fast: 80% after 12-18 hours. No wash out can be observed during the first 24 hours.

In hyperthyreosis, due to the increased hormone production, both the uptake and the wash out are faster: The uptake can reach 80% within 2-6 hours from the introduction, while the wash out is 50% and then 70% after 24 and 48 hours, respectively.

In hypothyreosis and in acute inflamed condition of the thyroid the uptake is of small extent and rate: hardly reaches 20% after 48 hours.

The biological half life of the wash out of I-131 from the body is 4 days in normal case, 1-3 days in hyperthyreosis.

5.3 Preclinical safety data

LD₅₀ value, which expresses the acute toxicity of I-131 introduced orally into the body is 1000 mg/kg body weight for mice and 760 mg/kg body weight for dogs (4). The optimum daily iodine requirement of adult humans is 0.15-0.30 mg/day (1). Since the specific activity of I-131-sodium-iodide is minimum 1 GBq/µg, the maximum iodine content of the highest possible dose administered to a patient (7.4 GBq) cannot exceed 7.4 µg, which is at most 2.4-4.9% of the optimum iodine intake. Therefore, it is obvious that the product can be considered safe in regard of iodine intake.

5.4 Radiophysical properties of the radionuclide and the absorbed dose values

The absorbed dose values caused by the introduced I-131-sodium-iodide in function of the maximum uptake in the thyroid are shown in the following table (5):

The I-131 product can contain radionuclide impurities only in quantity less than 0.1%.

References:

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

6.2 Incompatibilities

Above all, the product is incompatible with acids because in their presence radioiodide is converted into a volatile form (radical or elemental iodine), which – getting to the air – may cause a widespread radioactive contamination in the environment.

Furthermore, the product is incompatible with oxidising agents since they oxidise the present radioiodide (oxidation degree: -1) into elementary radioiodine (oxidation degree: 0), moreover, iodate (oxidation degree: +5) and periodate (oxidation degree: +7) ions may appear. Such components count as radiochemical impurities of the product, their formation is to be avoided.

Hindered I-131 uptake is disadvantageous both in case of thyroid scintigraphy and thyroid radionuclide therapy, therefore, introduction of inactive iodine is to be avoided. Such treatments are to be terminated prior to the administration of radioiodide according to the following table:

The clearance of radioiodide from the thyroid - in case of necessity - can be slowed down with lithium-carbonate. Colchicin also reduces the radioiodide clearance rate.

6.3 Shelf life

21 days from the day of production.

6.4 Special precautions for storage

The product is to be stored at room temperature (15-25°C); free from acidic vapours and oxidative agents; using appropriate radiation shielding. Storage conditions should be in accordance with the national regulations on radioactive materials.

6.5 Nature and composition of the packaging

I-131-sodium-iodide solution is supplied in a so-called lyophilising glass vial of 6 ml or 12 ml volume, closed with a rubber plug and an aluminium cap. A labelled lead pot, which is capped with a lead cover and lined with a paper cylinder as spacer, serves as radiation shielding. The glass vial is placed in the paper cylinder and this way in the lead container as well. The wall thickness of the lead pot varies between 15 and 30 mm according to the activity of the solution contained. The labelled lead container is put in a sealed and labelled metal can containing plastic foam spacers. The can can be easily opened by tearing the top panel.

6.6 Instruction for use and handling

One product represents the doses of several patients. The actual activities to be administered to the patients maybe very different from one another (50 MBq – 7.4 GBq). The individual activity values should be determined according to the procedure described in paragraph 4.2.

The product is a radioactive preparation, which should be opened truly according the following instructions:

During the operation the radiation safety regulations should be kept.

Tear off the top panel of the metal can. Remove the upper part of the plastic foam spacer. Lift the lead container out of the metal can and put it on the working area. Remove the seal strip and then the upper part of the lead pot. This way the glass vial containing the radioactive material is readily accessible.

The activity representing the dose of one patient is to be taken out of the vial with using a special injection syringe equipped with lead shielding. The activity value is to be verified with an appropriate measuring unit. The general mode of administration is intravenous injection.

In case of small activity per os (oral) administration is permitted, too. Such in case the solution in the syringe is injected to 100 ml drinking water. The patient drinks it and immediately also a glass of drinking water again (approximately 100 ml) so that the entire quantity of radioiodide remained in the mouth cavity, the pharynx and the esophagus is washed to the stomach.

7. MARKETING AUTHORISATION HOLDER

Institute of Isotopes Co., Ltd..
1121 Budapest, Konkoly Thege Miklós út 29-33.
1535 Budapest, P.O.B. 851.

8. NUMBER OF THE MARKETING AUTHORISATION

86.883.1973.

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Original Marketing Authorisation: September 26^th, 1973

10. DATE OF REVISION OF THE TEXT