Sodium Iodide (¹³¹I) Diagnostic Capsules 0.333-3.7 MBq capsules, hard

Sodium Iodide (¹³¹I) Diagnostic Capsules are presented as a white capsule. Each capsule contains 3.7 MBq (100 µ Ci) at the first reference date. At subsequent reference dates, at weekly intervals, the nominal activity per capsule is shown in the table below.

Iodine-131 is produced by fission of uranium-235 or by neutron bombardment of stable tellurium in a nuclear reactor. Iodine-131 has a half-life of 8.02 days. It decays by emission of gamma radiations of 365 keV (81.7%), 637 keV (7.2%) and 284 keV (6.1%) and beta radiations of maximal energy of 606 keV to stable Xenon131.

Excipients with known effect:

This medicinal product contains: 85.28mg of sodium per capsule. This needs to be taken into consideration by patients on a sodium controlled diet.

For the full list of excipients, see section 6.1.

Capsule, hard.

White, opaque gelatin capsule.

This medicinal product is for diagnostic use only.

1. Sodium [¹³¹I]iodide may be given as a “tracer” dose to study radioiodine kinetics. An estimation of the thyroid uptake and effective half life obtained with a tracer dose can be used to calculate the activity required for radioiodine therapy.

2. In the management of thyroid carcinoma, sodium [¹³¹I]iodide is used to identify thyroid remnants and metastases (after ablation).

3. Thyroid scanning for benign conditions with sodium [¹³¹I]iodide can be performed but only where circumstances do not allow for radiopharmaceuticals with more favourable dosimetry to be used.

Posology

Adults

The recommended activities for an adult patient (70 kg) are as follows:

1. For thyroid uptake studies: 0.2-3.7 MBq

2. For identification of metastases and thyroid remnants after thyroid ablation: a maximum activity of 400 MBq

3. For thyroid imaging: 7.4-11 MBq

Scans are usually performed at 4 hours, and then again at 18-24 hours (for scintigraphy also at 72 hours).

Elderly Population

No dose adjustment is recommended based on age.

Renal impairment

Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients .

Paediatric population

The diagnostic activity to be administered to a child over 10 years and adolescent should be a fraction of the adult dose calculated from the body weight/surface area methods according to the following equations:

Correction factors given for guidance are proposed below.

(Paediatric Task Group, European Association of Nuclear Medicines (EANM)).

Method of Administration

The capsule is administered orally together with a drink. It should be swallowed whole.

In patients with suspected gastrointestinal disease, great care should be taken when administering Sodium Iodide (¹³¹I) Diagnostic Capsules. The capsules should be swallowed whole with sufficient fluid to ensure clear passage into the stomach and upper small intestine. Concomitant use of H2 antagonists or proton pump inhibitors is advised.

For patient preparation, see section 4.4.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy

• For diagnostic purposes in children under 10 years of age.

• Thyroid scanning except in the follow-up of malignant disease or when iodine-123 or technetium-99m is not available.

• Patients with dysphagia, oesophageal stricture, active gastritis, gastric erosions and peptic ulcer.

• Patients with suspected reduced gastrointestinal motility.

Potential for hypersentitivity of 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 immediately available.

Individual benefit/risk justification:

For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic or therapeutic effect. Renal 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 sections 4.2.

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. Special precautions, such as urinary catheterisation, should be taken following administration of Sodium Iodide (¹³¹I) Diagnostic Capsules to patients who are significantly incontinent to minimise risks of radioactive contamination. International guidelines for disposal of radioactive waste must be followed.

Specific warnings:

There is no evidence of an increased incidence of malignancies (cancer, leukaemia or mutations) in man with patients treated for diagnostic purpose with sodium [¹³¹I]iodide.

This medicinal product contains 85.28mg of sodium per capsule. To be taken into consideration by patients on a controlled sodium diet.

For precautions with respect to environmental hazard see section 6.6.

A full drug history should be taken and relevant medication including the ones mentioned below should be withheld prior to the administration of sodium [¹³¹I]iodide.

* Due to the long half-life of amiodarone, iodine uptake in the thyroid tissue can be decreased for several months.

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

The use of Sodium [¹³¹I] iodide is contraindicated in pregnant women (see section 4.3). The absorbed dose to the uterus for this agent is likely to be in the range 11-511 mGy, and the foetal thyroid gland avidly concentrates iodine during the second and third trimesters.

Breastfeeding

Before administering radiopharmaceuticals 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 radiopharmaceuticals, bearing in mind the secretion of activity in breast milk.

Breastfeeding should be discontinued after sodium [¹³¹I] iodide administration.

For radioprotection reasons following therapeutic doses, it is recommended to avoid close contact between mother and child for at least one week.

No studies on the effect on the ability to drive or use machines have been performed.

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):

Diagnostic Indications:

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects.

For diagnostic use: As the effective dose is 24.4 mSv when the maximal recommended activity of 400 MBq is administered (thyroid blockage) these adverse reactions are expected to occur with a low probability.

In all cases it is necessary to ensure that the risks of the radiation are less than from the disease itself.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

High radiation exposure through overdose can be reduced by means of administration of thyroid blocking agent, such as potassium perchlorate, the use of emetics and promoting a diuresis with frequent voiding of urine.

Pharmacotherapeutic group: diagnostic radiopharmaceuticals, sodium [¹³¹I]iodide, ATC Code: V09FX03

Iodide, in the amount used for diagnostic indications, is not known to have any pharmacological effect. More than 90% of the radiation effects result from beta radiation which has a mean range of 0.5mm.

Distribution

After oral administration, sodium [¹³¹I]iodide is absorbed rapidly from the upper gastrointestinal tract (90% in 60 minutes). The pharmacokinetics follow that of unlabelled iodide.

Organ uptake

From the extra thyroidal compartment it is predominantly taken up by the thyroid or excreted renally. Small amounts of sodium [¹³¹I]iodide are taken up by salivary glands, gastric mucosa and would also be localised in breast milk, the placenta and choroids plexus.

Peak thyroid accumulation occurs within 24 – 48 hours of dosing with about 50% of the maximum at 5 hours. This kinetic profile provides the rationale for the diagnostics procedures at 24 and 72 hours after dosing.

Elimination

Urinary excretion is 37 – 75% faecal excretion is about 10% with almost negligible excretion in sweat.

Half-life

The effective half-life of radioiodine in plasma is in the order of 12 hours whereas that for radioiodine taken by the thyroid gland is about 6 days.

No acute toxicity is expected or observed.

There are no data available on the toxicity of repeated doses of sodium iodide nor on its effects on reproduction in animals or its mutagenic or carcinogenic potential.

Sodium thiosulphate, pentahydrate

Disodium phosphate, dihydrate

Sodium hydroxide

Water for injections

Capsule

Gelatin

Titanium dioxide (E171)

Sodium laurilsulfate

Acetic acid

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

The shelf life for this product is 5 weeks from the first activity reference date stated on the label.

Store below 25°C. Do not freeze.

Store in original lead container or in equivalent shielding.

Storage of radiopharmaceuticals should be in accordance with national regulations on radioactive materials.

The product is stored within a polystyrene container with a push-in cap made from polyethylene. This container is stored within a lead shield.

Pack size: Each pack contains 5 or 10 capsules.

Not all pack sizes may be marketed.

General warning

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 in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Administration procedures should be carried out in a way to minimise 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.

GE Healthcare Limited

Pollards Wood

Nightingales Lane

Chalfont St Giles

Buckinghamshire HP8 4SP

United Kingdom

PL 00221/0112

01/02/2010

September 2019

11. DOSIMETRY

The ICRP model refers to intravenous administration. Since absorption of radioiodide is rapid and complete, this model is applicable in case of oral administration also but there is a further radiation dose to the stomach wall in addition to that due to gastric and salivary excretion. Assuming that the mean residence time in the stomach is 0.5 hr, the absorbed dose to the stomach wall increase by about 30% for iodine-131 however the effective dose is virtually identical. Radiation dose to specific organs, which may not be the target organ of therapy can be influenced significantly by pathophysiological changes induced by the disease process.

As part of the risk-benefit assessment it is advised that the effective dose and likely radiation doses to individual target organ(s) be calculated prior to administration. The activity might then be adjusted according to thyroid mass, biological half-life and the “re-cycling” factor which takes into account the physiological status of the patient (including iodine depletion) and the underlying pathology.

The tables below show the dosimetry as calculated according to the Publication 53 and 60 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals).

Iodide ((¹³¹I); half life 8.02 days)

Thyroid blocked, uptake 0%

Bladder wall contributes to 50.0% of the effective dose.

Incomplete blockage:

Effective dose (mSv/MBq) with little uptake in the thyroid.

Thyroid uptake 15%

Thyroid uptake 35%

Thyroid uptake 55%

12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

The product is a capsule for oral administration and should be used according to section 4.2.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.