Sodium Iodide (123i) Injection 37 Mbq/Ml Solution For Injection
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
123
Sodium Iodide ( I) Injection 37 MBq/ml solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Sodium [123I]iodide, 37 MBq/ml at reference date and hour.
At calibration time, the radionuclidic purity is at least 99.9% and the main radio-nuclidic impurities (iodine-125 and tellurium-121) occur for less then 0.05%.
Iodine-123 is a cyclotron product with a physical half-life of 13.2 hours. Iodine-123 decays emitting pure gamma radiation with predominant energies of 159 keV and 27 keV.
This medicinal product contains sodium: 3.99 mg/ml.
For a full list of excipients, see section 6.1.
The contents of the vial may be used for one or more administrations until time of expiry.
3 PHARMACEUTICAL FORM
Solution for injection Clear, colourless solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
Sodium Iodide ( I) Injection is used as a diagnostic agent in the functional or morphological study of the thyroid gland by means of:
• scintigraphy
• radioactive iodine uptake test
The 24 hours uptake data are generally used in calculating the therapeutic dose.
The recommended activity for an adult patient (70 kg) is between 3.7 and 14.8 MBq. The lower activity (3.7 MBq) is recommended for uptake studies and the higher doses (11.1 - 14.8 MBq) for thyroid scintigraphy. However, for each individual case, the dose is decided by the specialist concerned.
Determination of the rate of thyroid iodine-123 uptake should be carried out in accordance with well established standard procedures.
The activities for children may be calculated from the recommended range of adult activities and adjusted according to the following equation:
Activity-child (MBq) = activity adult (MBq) x body weight (kg)
70 (kg)
In young children, the activity of 14.8 MBq should be used in the equation to calculate the activity for children in order to obtain images of sufficient quality. Sodium Iodide (123I) Injection must be given as an intravenous injection; as a routine check, the activity in the injection should be measured immediately prior to administration. Imaging is performed 3-6 hours after administration.
The instructions for preparation of radiopharmaceuticals are given in section 12.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4. Special warnings and precautions for use
Individual benefit/risk justification:
For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.
Paediatric population:
Paediatric population, see section 4.2
General warnings:
Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent official organisation.
Radiopharmaceuticals should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.
Specific warnings:
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.
4.5 Interaction with other medicinal products and other forms of interaction
The uptake of [123I] iodide maybe decreased by recent administration of iodinated contrast materials, by intake of stable iodine in any form, or by thyroid, antithyroid, and certain other drugs.
Accordingly, the patient should be questioned carefully regarding diet, previous medication, and procedures involving radiographic contrast media. Relevant medication including the ones mentioned below should be withheld prior to the administration of sodium [123I] iodide.
Active substances: Withdrawal period prior to administration of sodium [123I ]iodide Antithyroid agents (e.g. carbimazole, methimazole, propyluracil), perchlorate: 1 week. Salicylates, steroids, sodium nitroprusside, sodium sulfobromophthalein, anticoagulants, antihistamines, antiparasitics, penicillins, sulfonamides tolbutamide, thiopental: 1 week. Phenylbutazone: 1-2 weeks.
Expectorants and vitamins: 2 weeks.
Natural or synthetic thyroid preparations (levothyroxine sodium, liothyronine sodium): 2-3 weeks.
Amiodarone, benzodiazepines, lithium: approx. 4 weeks.
Iodine-containing preparations for topical use: 1-9 months.
Intravenous contrast agents: 1-2 months Iodine containing contrast agent: up to 1 year.
4.6. Pregnancy and lactation
Women of childbearing potential:
When it is necessary to administer radioactive medicinal product to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.
Pregnancy:
Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only imperative investigations should be carried out during pregnancy, when the likely benefit exceeds the risk incurred by the mother and foetus.
Breast-feeding:
Before administering a radioactive medicinal product to a mother who is breastfeeding consideration should be given as to whether the investigation could be reasonably delayed until the mother has ceased breast-feeding and to what is the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretion activity in breast milk.
If the administration is found necessary the breast-feeding should be interrupted for
1.5 - 3 days following the administration of iodine-123 that contains iodine-125 and/or iodine-124 as radio contaminant. Expressed milk should be discarded.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8. Undesirable effects
The frequencies of undesirable effects are defined as follows:
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) and not known (cannot be estimated from the available data).
Immune system disorders Not known: Hypersensitivity
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defect. As the effective dose is 2.2 mSv when the maximal recommended activity of 14.8 MBq is administered these adverse events are expected to occur with a low probability.
4.9. Overdose
In the event of the administration of an overdose of [123I]iodide, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by diuresis and frequent voiding of urine. A blocking agent such as potassium perchlorate should be used to minimise irradiation to the thyroid.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, thyroid, sodium iodide (123I), ATC code: V09FX02.
At doses used in diagnostic investigations, sodium iodide has not been observed to exert any pharmacodynamic effects.
5.2 Pharmacokinetic properties
Intravenously administered iodide is taken by the thyroid. About 20% of the available radioactivity enters the thyroid in one pass of the blood volume. Normal thyroid clearance of blood iodide is 20-50 ml/min with an increase to 100 ml/min in thyroid deficiency.
Peak levels of iodide occur in thyroid gland within a few hours so that diagnostic imaging can take place from one hour after dosing.
The half-time of iodide elimination from the thyroid is estimated at 80 days so that the physical half-life of iodine-123 of 13 hours governs the temporal opportunity for imaging.
Without considering the thyroid uptake, the iodide leaves the body stream chiefly by urinary excretion (37-75%), while faecal excretion is low (about 1%).
5.3 Preclinical safety data
Known toxic effects of relatively high doses of sodium iodide are not relevant to this use of iodine-123 to image the thyroid for diagnostic purposes.
No data are available from animal models about toxicity with repeated dose administration or about reproduction toxicity.
Sodium Iodide ( I) Injection has not been investigated for mutagenicity and carcinogenic/oncogeni c potential.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Acetic acid Sodium hydroxide Sodium thiosulphate Sodium bicarbonate Sodium chloride Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
Can be used up to 36 hours post calibration time indicated on the label.
Once opened store in a refrigerator (2°C-8°C) and use within one working day.
6.4 Special precautions for storage
Store below 25°C. Do not freeze.
For storage conditions of the opened medicinal product, see section 6.3.
Store either in original lead container or in equivalent shielding.
Storage should be in accordance with national regulations for radioactive materials.
10 ml medicinal glass vial, closed with a Teflon coated rubber stopper and sealed with an aluminium cap. Each vial is enclosed in a lead container of appropriate thickness.
Pack size: 18.5 to 370 MBq.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Normal safety precautions for handling radioactive materials should be observed. After use, all materials associated with the preparation and administration of radiopharmaceuticals, including any unused product and its container, should be decontaminated or treated as radioactive waste and disposed of in accordance with the conditions specified by the local competent authority. Contaminated material must be disposed of as radioactive waste via an authorised route.
7 MARKETING AUTHORISATION HOLDER
GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 00221/0138
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 01 December 1998 Date of last renewal: 23 May 2003
10 DATE OF REVISION OF THE TEXT
13/05/2011
11 DOSIMETRY (IF APPLICABLE)
Depending on the production, procedure of iodine -123, impurities like iodine-125 and/or iodine-124 may be present as longer life contaminants increasing the radiation dosimetry to the different organs. The ICRP model refers to intravenous administration.
For this product, the effective dose equivalent resulting from an administered activity of 14.8 MBq will be 2.2 mSv. This effective dose equivalent is dependent on the uptake in the thyroid glands.
The effective (whole body) dose equivalent is calculated from the six standard organs (gonads, breast, red marrow, lungs, thyroid and bone surfaces) and five additional organs with the highest absorbed dose (marked with *).
The table below shows the dosimetry as calculated according to the Publication 53 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals, Pergamon Press 1987).
|
Organ |
Absorbed dose p |
er unit activ mGy/MBq' |
ity administered | ||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
7.0E-03 |
8.7E-03 |
1.4E-02 |
2.1E-02 |
3.9E-02 |
|
* Bladder wall |
9.0E-02 |
1.1E-01 |
1.6E-01 |
2.4E-01 |
4.5E-01 |
|
Bone surfaces |
8.1E-03 |
9.7E-03 |
1.5E-02 |
2.4E-02 |
4.6E-02 |
|
Breast GI-tract: |
5.6E-03 |
5.6E-03 |
8.1E-03 |
1.3E-02 |
2.5E-02 |
|
Stomach wall |
6.9E-03 |
8.5E-03 |
1.4E-02 |
2.1E-02 |
3.7E-02 |
|
* Small intest |
8.5E-03 |
1.0E-02 |
1.6E-02 |
2.5E-02 |
4.6E-02 |
|
* ULI wall |
8.0E-03 |
9.9E-03 |
1.5E-02 |
2.4E-02 |
4.3E-02 |
|
* LLI wall |
9.7E-03 |
1.2E-02 |
1.9E-02 |
2.9E-02 |
5.4E-02 |
|
* Kidneys |
1.1E-02 |
1.4E-02 |
2.0E-02 |
2.9E-02 |
5.1E-02 |
|
Liver |
6.7E-03 |
8.2E-03 |
1.3E-02 |
2.0E-02 |
3.7E-02 |
|
Lungs |
6.1E-03 |
7.8E-03 |
1.2E-02 |
1.9E-02 |
3.5E-02 |
|
Ovaries |
9.8E-03 |
1.2E-02 |
1.9E-02 |
3.0E-02 |
5.3E-02 |
|
Pancreas |
7.6E-03 |
9.1E-03 |
1.4E-02 |
2.2E-02 |
4.1E-02 |
|
Red marrow |
9.4E-03 |
1.1E-02 |
1.7E-02 |
2.6E-02 |
4.7E-02 |
|
Spleen |
7.0E-03 |
8.3E-03 |
1.3E-02 |
2.0E-02 |
3.7E-02 |
|
Testes |
6.9E-03 |
9.4E-03 |
1.5E-02 |
2.5E-02 |
4.8E-02 |
|
Thyroid |
5.1E-03 |
7.7E-03 |
1.2E-02 |
2.0E-02 |
3.7E-02 |
|
Uterus |
1.4E-02 |
1.7E-02 |
2.8E-02 |
4.3E-02 |
7.6E-02 |
|
Other tissue |
6.4E-03 |
7.7E-03 |
1.2E-02 |
1.9E-02 |
3.5E-02 |
|
Effective dose equivalent (mSv/MBq) |
1.3E-02 |
1.6E-02 |
2.4E-02 |
3.7E-02 |
6.7E-02 |
Incomplete blockage:
Effective dose equivalent (mSv/MBq) at small uptake in the thyroid
|
uptake: |
0.5% |
1.6E-02 |
2.0E-02 |
3.1E-02 |
5.2E-02 |
9.6E-02 |
|
uptake: |
1.0% |
1.9E-02 |
2.5E-02 |
3.8E-02 |
6.7E-02 |
1.3E-01 |
|
uptake: |
2.0% |
2.5E-02 |
3.4E-02 |
5.2E-02 |
9.9E-02 |
1.8E-01 |
Effect of radionuclidic impurities:
The radionuclidic impurities (iodine-125 and tellurium-121) increase the effective dose equivalent with approximately 0.5% at calibration time and 3% at expiration time.
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
6.3E-03 |
8.3E-03 |
1.3E-02 |
2.0E-02 |
3.7E-02 |
|
* Bladder wall |
7.6E-02 |
9.5E-02 |
1.4E-01 |
2.1E-01 |
3.8E-01 |
|
Bone surfaces |
7.1E-03 |
9.1E-03 |
1.4E-02 |
2.2E-02 |
4.1E-02 |
|
Breast GI-tract: |
4.7E-03 |
4.7E-03 |
7.3E-03 |
1.2E-02 |
2.3E-02 |
|
* Stomach wall |
6.8E-02 |
8.5E-02 |
1.2E-01 |
2.0E-01 |
3.8E-01 |
|
* Small intest |
4.3E-02 |
5.4E-02 |
9.1E-02 |
1.4E-01 |
2.7E-01 |
|
* ULI wall |
1.8E-02 |
1.9E-02 |
2.9E-02 |
4.5E-02 |
7.7E-02 |
|
LLI wall |
1.1E-02 |
1.4E-02 |
2.2E-02 |
3.3E-02 |
6.0E-02 |
|
Kidneys |
1.0E-02 |
1.3E-02 |
1.8E-02 |
2.7E-02 |
4.6E-02 |
|
Liver |
6.2E-03 |
7.6E-03 |
1.3E-02 |
2.1E-02 |
3.8E-02 |
|
Lungs |
5.7E-03 |
7.2E-03 |
1.1E-02 |
1.8E-02 |
3.4E-02 |
|
Ovaries |
1.2E-02 |
1.6E-02 |
2.5E-02 |
3.8E-02 |
6.8E-02 |
|
* Pancreas |
1.4E-02 |
1.6E-02 |
2.4E-02 |
3.5E-02 |
6.1E-02 |
|
Red marrow |
9.4E-03 |
1.2E-02 |
1.7E-02 |
2.5E-02 |
4.3E-02 |
|
Spleen |
9.5E-03 |
1.1E-02 |
1.7E-02 |
2.5E-02 |
4.4E-02 |
|
Testes |
5.3E-03 |
7.2E-03 |
1.2E-02 |
2.0E-02 |
3.8E-02 |
|
Thyroid |
1.9E+00 |
3.0E+00 |
4.5E+00 |
9.8E+00 |
1.9E+01 |
|
Uterus |
1.5E-02 |
1.9E-02 |
3.1E-02 |
4.9E-02 |
8.6E-02 |
|
Other tissue |
6.8E-03 |
8.5E-03 |
1.3E-02 |
2.1E-02 |
3.9E-02 |
|
Effective dose equivalent (mSv/MBq) |
7.5E-02 |
1.1E-01 |
1.7E-01 |
3.5E-01 |
6.5E-01 |
Effect of radionuclidic impurities:
The radionuclidic impurities (iodine-125 and tellurium-121) increase the effective dose equivalent with approximately 0.6% at calibration time and 4% at expiration time.
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
6.5E-03 |
8.4E-03 |
1.3E-02 |
2.1E-02 |
3.8E-02 |
|
* Bladder wall |
6.0E-02 |
7.4E-02 |
1.1E-01 |
1.6E-01 |
3.0E-01 |
|
Bone surfaces |
7.9E-03 |
1.1E-02 |
1.6E-02 |
2.5E-02 |
4.6E-02 |
|
Breast GI-tract: |
5.2E-03 |
5.2E-03 |
8.5E-03 |
1.5E-02 |
2.7E-02 |
|
* Stomach wall |
6.8E-02 |
8.5E-02 |
1.2E-01 |
2.0E-01 |
3.8E-01 |
|
* Small intest |
4.2E-02 |
5.4E-02 |
9.0E-02 |
1.4E-01 |
2.7E-01 |
|
* ULI wall |
1.8E-02 |
1.9E-02 |
2.9E-02 |
4.5E-02 |
7.6E-02 |
|
LLI wall |
1.0E-02 |
1.4E-02 |
2.1E-02 |
3.2E-02 |
5.8E-02 |
|
Kidneys |
9.1E-03 |
1.1E-02 |
1.6E-02 |
2.4E-02 |
4.1E-02 |
|
Liver |
6.3E-03 |
7.8E-03 |
1.3E-02 |
2.1E-02 |
4.0E-02 |
|
Lungs |
6.5E-03 |
8.6E-03 |
1.4E-02 |
2.2E-02 |
4.2E-02 |
|
Ovaries |
1.1E-02 |
1.5E-02 |
2.4E-02 |
3.7E-02 |
6.6E-02 |
|
* Pancreas |
1.4E-02 |
1.6E-02 |
2.4E-02 |
3.6E-02 |
6.2E-02 |
|
Red marrow |
1.0E-02 |
1.3E-02 |
1.9E-02 |
2.8E-02 |
4.8E-02 |
|
Spleen |
9.6E-03 |
1.1E-02 |
1.7E-02 |
2.5E-02 |
4.5E-02 |
|
Testes |
5.0E-03 |
6.8E-03 |
1.1E-02 |
1.8E-02 |
3.5E-02 |
|
Thyroid |
4.5E+00 |
7.0E+00 |
1.1E+01 |
2.3E+01 |
4.3E+01 |
|
Uterus |
1.4E-02 |
1.7E-02 |
2.9E-02 |
4.4E-02 |
7.9E-02 |
|
Other tissue |
8.0E-03 |
1.0E-02 |
1.6E-02 |
2.6E-02 |
4.9E-02 |
|
Effective dose equivalent (mSv/MBq) |
1.5E-01 |
2.3E-01 |
3.5E-01 |
7.4E-01 |
1.4E+00 |
Effect of radionuclidic impurities:
The radionuclidic impurities (iodine-125 and tellurium-121) increase the effective dose equivalent with approximately 0.6% at calibration time and 4% at expiration time.
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
6.5E-03 |
8.5E-03 |
1.4E-02 |
2.1E-02 |
3.9E-02 |
|
Bladder wall |
4.3E-02 |
5.3E-02 |
7.9E-02 |
1.2E-01 |
2.2E-01 |
|
Bone surfaces |
8.6E-03 |
1.2E-02 |
1.8E-02 |
2.8E-02 |
5.1E-02 |
|
Breast GI-tract: |
5.6E-03 |
5.6E-03 |
9.5E-03 |
1.7E-02 |
3.1E-02 |
|
* Stomach wall |
6.8E-02 |
8.5E-02 |
1.2E-01 |
2.0E-01 |
3.9E-01 |
|
* Small intest |
4.2E-02 |
5.4E-02 |
9.1E-02 |
1.4E-01 |
2.7E-01 |
|
* ULI wall |
1.8E-02 |
1.9E-02 |
2.9E-02 |
4.4E-02 |
7.6E-02 |
|
LLI wall |
9.8E-03 |
1.3E-02 |
2.0E-02 |
3.0E-02 |
5.5E-02 |
|
Kidneys |
9.1E-03 |
1.1E-02 |
1.6E-02 |
2.4E-02 |
4.1E-02 |
|
Liver |
6.4E-03 |
7.9E-03 |
1.3E-02 |
2.2E-02 |
4.1E-02 |
|
Lungs |
7.2E-03 |
9.7E-03 |
1.6E-02 |
2.6E-02 |
4.8E-02 |
|
Ovaries |
1.1E-02 |
1.5E-02 |
2.3E-02 |
3.6E-02 |
6.4E-02 |
|
* Pancreas |
1.4E-02 |
1.6E-02 |
2.5E-02 |
3.6E-02 |
6.3E-02 |
|
Red marrow |
1.1E-02 |
1.5E-02 |
2.1E-02 |
3.0E-02 |
5.2E-02 |
|
Spleen |
9.7E-03 |
1.1E-02 |
1.7E-02 |
2.6E-02 |
4.6E-02 |
|
Testes |
4.6E-03 |
6.2E-03 |
1.0E-02 |
1.6E-02 |
3.2E-02 |
|
Thyroid |
7.0E+00 |
1.1E+01 |
1.7E+01 |
3.6E+01 |
6.8E+01 |
|
Uterus |
1.2E-02 |
1.6E-02 |
2.6E-02 |
4.0E-02 |
7.2E-02 |
|
Other tissue |
9.2E-03 |
1.2E-02 |
1.9E-02 |
3.1E-02 |
5.8E-02 |
|
Effective dose equivalent (mSv/MBq) |
2.3E-01 |
3.5E-01 |
5.3E-01 |
1.1E+00 |
2.1E+00 |
Effect of radionuclidic impurities:
The radionuclidic impurities (iodine-125 and tellurium-121) increase the effective dose equivalent with approximately 0.6% at calibration time and 4% at expiration time.
12 INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)
This radiopharmaceutical may be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the local competent official organisations (see section 6.6).
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.
Solution for intravenous injection, ready to use.
Aseptic conditions must be observed during withdrawal of a patient dose from the vial, including microbial decontamination of the rubber stopper with a suitable disinfectant before removal of a dose. This product is not preserved. After removal of a dose from the vial, store at 2°C-8°C and use within one working day.