Summary of Product Characteristics (SmPC) - Sodium Iodide (123I) injection, 37 MBq/ml solution for injection
1 NAME OF THE MEDICINAL PRODUCT
Sodium Iodide (123I) 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 radionuclidic 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.
Excipient(s) with known effect:
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 (123I) 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.
4.2 Posology and method of administration
Posology
Adults
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.
Paediatric population
The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group.
The activities to be administered to children and to adolescents 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.
Renal/Hepatic impairment
Sodium Iodide has not been studied in patients with significant renal or hepatic impairment. Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.
Method of administration
For instructions on preparation of the medicinal product before administration, see section 12.
For patient preparation, see section 4.4.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Potential for hypersensitivity or anaphylactic reactions:
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies the necessary medicinal products and equipment such as endotracheal tube and ventilator must be readily available.
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.
Renal/Hepatic impairment:
Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.
Paediatric population:
For information on the use in paediatric population, see section 4.2.
Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).
Patient preparation:
The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the examination in order to reduce radiation.
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.
Specific warnings:
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.
Precautions with respect to environmental hazard see section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
The uptake of [123I] iodide may be 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.
Paediatric population
Interaction studies have only been performed in adults.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential:
When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. 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 essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus.
Breastfeeding:
Before administering a radiopharmaceutical to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding and to what is the most appropriate choice of radiopharmaceutical, bearing in mind the secretion of activity in breast milk.
If the administration is considered necessary, breastfeeding 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 feeds should be discarded.
Fertility:
No studies on fertility have been performed.
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 reactions are expected to occur with a low probability.
Paediatric population
No data are available
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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.
Paediatric population
No data are available.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, thyroid, sodium iodide (123I), ATC code: V09FX02.
Pharmacodynamic effects
At doses used in diagnostic investigations, sodium iodide has not been observed to exert any pharmacodynamic effects.
Clinical efficacy and safety
See Pharmacodynamic effects.
Paediatric population
No data are available.
5.2 Pharmacokinetic properties
Distribution
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.
Organ Uptake
Peak levels of iodide occur in thyroid gland within a few hours so that diagnostic imaging can take place from one hour after dosing.
Elimination
See Half-life.
Half-life
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%).
Renal/Hepatic impairment
The pharmacokinetics in patients with renal or hepatic impairments has not been characterised.
Paediatric population
No data are available.
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 (123I) Injection has not been investigated for mutagenicity and carcinogenic/oncogenic 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 after the first opening of the medicinal product, see section 6.3.
Store either in the original lead container or in equivalent shielding.
Storage of radiopharmaceuticals should be in accordance with national regulations on radioactive materials.
6.5 Nature and contents of container
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
General warning
Radiopharmaceuticals should be received, used and administered only by authorized persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the competent official organization.
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken. If at any time in the preparation of this product the integrity of this container is compromised it should not be used.
Administration procedures should be carried out in a way to minimize risk of contamination of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Pollards Wood
Nightingales Lane
Chalfont St Giles
Buckinghamshire HP8 4SP
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
10/08/2020
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).
Thyroid blocked, uptake 0%
| Organ | Absorbed dose per unit activity administered (mGy/MBq) | ||||
| Adult | 15 year | 10 year | 5 year | 1 year | |
Adrenals * Bladder wall Bone surfaces Breast GI-tract: Stomach wall * Small intest * ULI wall * LLI wall * Kidneys Liver Lungs Ovaries Pancreas Red marrow Spleen Testes Thyroid Uterus Other tissue | 7.0E-03 9.0E-02 8.1E-03 5.6E-03 6.9E-03 8.5E-03 8.0E-03 9.7E-03 1.1E-02 6.7E-03 6.1E-03 9.8E-03 7.6E-03 9.4E-03 7.0E-03 6.9E-03 5.1E-03 1.4E-02 6.4E-03 | 8.7E-03 1.1E-01 9.7E-03 5.6E-03 8.5E-03 1.0E-02 9.9E-03 1.2E-02 1.4E-02 8.2E-03 7.8E-03 1.2E-02 9.1E-03 1.1E-02 8.3E-03 9.4E-03 7.7E-03 1.7E-02 7.7E-03 | 1.4E-02 1.6E-01 1.5E-02 8.1E-03 1.4E-02 1.6E-02 1.5E-02 1.9E-02 2.0E-02 1.3E-02 1.2E-02 1.9E-02 1.4E-02 1.7E-02 1.3E-02 1.5E-02 1.2E-02 2.8E-02 1.2E-02 | 2.1E-02 2.4E-01 2.4E-02 1.3E-02 2.1E-02 2.5E-02 2.4E-02 2.9E-02 2.9E-02 2.0E-02 1.9E-02 3.0E-02 2.2E-02 2.6E-02 2.0E-02 2.5E-02 2.0E-02 4.3E-02 1.9E-02 | 3.9E-02 4.5E-01 4.6E-02 2.5E-02 3.7E-02 4.6E-02 4.3E-02 5.4E-02 5.1E-02 3.7E-02 3.5E-02 5.3E-02 4.1E-02 4.7E-02 3.7E-02 4.8E-02 3.7E-02 7.6E-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.
Thyroid blocked, uptake 15%
| Organ | Absorbed dose per unit activity administered (mGy/MBq) | ||||
| Adult | 15 year | 10 year | 5 year | 1 year | |
Adrenals * Bladder wall Bone surfaces Breast GI-tract: * Stomach wall * Small intest * ULI wall LLI wall Kidneys Liver Lungs Ovaries * Pancreas Red marrow Spleen Testes Thyroid Uterus Other tissue | 6.3E-03 7.6E-02 7.1E-03 4.7E-03 6.8E-02 4.3E-02 1.8E-02 1.1E-02 1.0E-02 6.2E-03 5.7E-03 1.2E-02 1.4E-02 9.4E-03 9.5E-03 5.3E-03 1.9E+00 1.5E-02 6.8E-03 | 8.3E-03 9.5E-02 9.1E-03 4.7E-03 8.5E-02 5.4E-02 1.9E-02 1.4E-02 1.3E-02 7.6E-03 7.2E-03 1.6E-02 1.6E-02 1.2E-02 1.1E-02 7.2E-03 3.0E+00 1.9E-02 8.5E-03 | 1.3E-02 1.4E-01 1.4E-02 7.3E-03 1.2E-01 9.1E-02 2.9E-02 2.2E-02 1.8E-02 1.3E-02 1.1E-02 2.5E-02 2.4E-02 1.7E-02 1.7E-02 1.2E-02 4.5E+00 3.1E-02 1.3E-02 | 2.0E-02 2.1E-01 2.2E-02 1.2E-02 2.0E-01 1.4E-01 4.5E-02 3.3E-02 2.7E-02 2.1E-02 1.8E-02 3.8E-02 3.5E-02 2.5E-02 2.5E-02 2.0E-02 9.8E+00 4.9E-02 2.1E-02 | 3.7E-02 3.8E-01 4.1E-02 2.3E-02 3.8E-01 2.7E-01 7.7E-02 6.0E-02 4.6E-02 3.8E-02 3.4E-02 6.8E-02 6.1E-02 4.3E-02 4.4E-02 3.8E-02 1.9E+01 8.6E-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.
Thyroid blocked, uptake 35%
| Organ | Absorbed dose per unit activity administered (mGy/MBq) | ||||
| Adult | 15 year | 10 year | 5 year | 1 year | |
Adrenals * Bladder wall Bone surfaces Breast GI-tract: * Stomach wall * Small intest * ULI wall LLI wall Kidneys Liver Lungs Ovaries * Pancreas Red marrow Spleen Testes Thyroid Uterus Other tissue | 6.5E-03 6.0E-02 7.9E-03 5.2E-03 6.8E-02 4.2E-02 1.8E-02 1.0E-02 9.1E-03 6.3E-03 6.5E-03 1.1E-02 1.4E-02 1.0E-02 9.6E-03 5.0E-03 4.5E+00 1.4E-02 8.0E-03 | 8.4E-03 7.4E-02 1.1E-02 5.2E-03 8.5E-02 5.4E-02 1.9E-02 1.4E-02 1.1E-02 7.8E-03 8.6E-03 1.5E-02 1.6E-02 1.3E-02 1.1E-02 6.8E-03 7.0E+00 1.7E-02 1.0E-02 | 1.3E-02 1.1E-01 1.6E-02 8.5E-03 1.2E-01 9.0E-02 2.9E-02 2.1E-02 1.6E-02 1.3E-02 1.4E-02 2.4E-02 2.4E-02 1.9E-02 1.7E-02 1.1E-02 1.1E+01 2.9E-02 1.6E-02 | 2.1E-02 1.6E-01 2.5E-02 1.5E-02 2.0E-01 1.4E-01 4.5E-02 3.2E-02 2.4E-02 2.1E-02 2.2E-02 3.7E-02 3.6E-02 2.8E-02 2.5E-02 1.8E-02 2.3E+01 4.4E-02 2.6E-02 | 3.8E-02 3.0E-01 4.6E-02 2.7E-02 3.8E-01 2.7E-01 7.6E-02 5.8E-02 4.1E-02 4.0E-02 4.2E-02 6.6E-02 6.2E-02 4.8E-02 4.5E-02 3.5E-02 4.3E+01 7.9E-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.
Thyroid blocked, uptake 55%
| Organ | Absorbed dose per unit activity administered (mGy/MBq) | ||||
| Adult | 15 year | 10 year | 5 year | 1 year | |
Adrenals Bladder wall Bone surfaces Breast GI-tract: * Stomach wall * Small intest * ULI wall LLI wall Kidneys Liver Lungs Ovaries * Pancreas Red marrow Spleen Testes Thyroid Uterus Other tissue | 6.5E-03 4.3E-02 8.6E-03 5.6E-03 6.8E-02 4.2E-02 1.8E-02 9.8E-03 9.1E-03 6.4E-03 7.2E-03 1.1E-02 1.4E-02 1.1E-02 9.7E-03 4.6E-03 7.0E+00 1.2E-02 9.2E-03 | 8.5E-03 5.3E-02 1.2E-02 5.6E-03 8.5E-02 5.4E-02 1.9E-02 1.3E-02 1.1E-02 7.9E-03 9.7E-03 1.5E-02 1.6E-02 1.5E-02 1.1E-02 6.2E-03 1.1E+01 1.6E-02 1.2E-02 | 1.4E-02 7.9E-02 1.8E-02 9.5E-03 1.2E-01 9.1E-02 2.9E-02 2.0E-02 1.6E-02 1.3E-02 1.6E-02 2.3E-02 2.5E-02 2.1E-02 1.7E-02 1.0E-02 1.7E+01 2.6E-02 1.9E-02 | 2.1E-02 1.2E-01 2.8E-02 1.7E-02 2.0E-01 1.4E-01 4.4E-02 3.0E-02 2.4E-02 2.2E-02 2.6E-02 3.6E-02 3.6E-02 3.0E-02 2.6E-02 1.6E-02 3.6E+01 4.0E-02 3.1E-02 | 3.9E-02 2.2E-01 5.1E-02 3.1E-02 3.9E-01 2.7E-01 7.6E-02 5.5E-02 4.1E-02 4.1E-02 4.8E-02 6.4E-02 6.3E-02 5.2E-02 4.6E-02 3.2E-02 6.8E+01 7.2E-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)
Method of preparation
Solution for intravenous injection, ready to use.
Quality control
Withdrawals should be performed under aseptic conditions. The vials must not be opened disinfecting the stopper, the solution should be withdrawn via the stopper using a single dose syringe fitted with suitable protective shielding and a disposable sterile needle or using an authorised automated application system.
If the integrity of this vial is compromised, the product should not be used.
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.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements (see section 6.6).