SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Sodium Iodide (¹³¹I) Injection 74 MBq/ml and 925 MBq/ml solution for injection

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

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Sodium Iodide ( I) Injection is a clear, colourless solution containing sodium [¹³¹I]iodide:

37-740 MBq/vial (74 MBq/ml) at the activity reference date

0.925-9.25 GBq/vial (925 MBq/ml) at the activity reference date

The specific activity of the sodium [ I]_iodide is not less than 222 GBq/mg iodine at the activity reference date.

Iodine-131 is produced by fission of uranium-235 or by neutron bombardment of stable tellurium in a nuclear reactor. It decays by emission of gamma radiations of 365 keV (81.7%), 637 keV (7.2%) and 284 (6.1%) and beta radiations of maximal energy of 0.606 MeV to stable Xenon-131. Iodine-131 has a half-life of 8.02 days.

This medicinal product contains 5.92 mg/ml sodium. This needs to be taken into consideration for patients on a controlled sodium diet.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Diagnostic indications

Sodium 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 amount can be used to calculate the activity required for radioiodine therapy.

In the management of thyroid carcinoma, sodium iodide is used to identify thyroid remnant and metastases (after ablation).

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.

Therapeutic indications

Radioiodide thyroid therapy is indicated for:

•    treatment of Grave’s disease, toxic multinodular goitre or autonomous nodules

•    treatment of papillary and follicular thyroid carcinoma including metastatic disease.

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Sodium [ I] iodide therapy is often combined with surgical intervention and with antithyroid medications.

4.2 Posology and method of administration

Diagnostic use

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

1.    For the thyroid uptake studies: 0.2-3.7 MBq.

2.    For post thyroid ablation (for metastases and thyroid remnant): a maximum dose 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).

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

	Adult dose (MBq) x child weight (kg)
paediatric dose (MBq)	70 kg

	Adult dose (MBq) x child surface (m )
paediatric dose (MBq)	1.73 m2

Correction factors given for guidance are proposed below:

Fraction oi		' adult dose
3 kg	=	0.10	22kg	=	0.50	42 kg	=	0.78
4 kg	=	0.14	24kg	=	0.53	44 kg	=	0.80
6 kg	=	0.19	26kg	=	0.56	46 kg	=	0.82
8 kg	=	0.23	28kg	=	0.58	48 kg	=	0.85
10kg	=	0.27	30kg	=	0.62	50 kg	=	0.88
12kg	=	0.32	32kg	=	0.65	52-54 kg	=	0.90
14kg	=	0.36	34kg	=	0.68	56-58 kg	=	0.92
16kg	=	0.40	36kg	=	0.71	60-62 kg	=	0.96
18kg	=	0.44	38kg	=	0.73	64-66 kg	=	0.98

20kg

=

0.46

40 kg

=

0.76

68 kg

=

0.99

(Paediatric Task Group, European Association of Nuclear Medicines) Therapeutic use

The activity administered is a matter for clinical judgement. The therapeutic effect is only achieved after several months.

•    For the treatment of hyperthyroidism

The activity administered is usually in the range of 200-800 MBq but repeated treatment may be necessary, with cumulative activities of up to 5000 MBq. The dose required depends on the diagnosis, the size of the gland, thyroid uptake and iodine clearance. Patients should be rendered euthyroid medically whenever possible before giving radioiodine treatment for hyperthyroidism.

•    For thyroid ablation and treatment of metastases

The administered activities following total or sub total thyroidectomy to ablate remaining thyroid tissue are in the range of 1850-3700 MBq. It depends on the remnant size and radioiodine uptake. In subsequent treatment for metastases, administered activity is in the range 3700-11100 MBq.

After high doses used, e.g. for the treatment of thyroid carcinoma, patients should be encouraged to increase oral fluids to have frequent bladder emptying to reduce bladder radiation.

The therapeutic activity to be administered to a child over 10 years and adolescent should be a fraction of the adult dose, calculated from body weight or surface area.

4.3 Contraindications

•    Hypersensitivity to the active substance or to any of the excipients.

•    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.

4.4 Special warnings and precautions for use

The possibility of hypersensitivity including anaphylactic / anaphylactoid reactions should always be considered. Advanced life support facilities should be readily available.

The administration of high dose radioiodine may result in significant environmental hazard. Suitable precautions should be taken concerning the activity eliminated by the patients in order to avoid any contamination.

The therapeutic administration of sodium [ I] iodide in patients with significant renal impairment requires special attention with regards to administered activity.

Sperm banking should be considered for young men who have extensive disease and therefore may need high radioiodine therapeutic doses.

Contraception for 6 months (for patients with benign thyroid conditions) or 12 months (for patients with thyroid cancer) is recommended for both sexes after

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therapeutic administration of sodium [ I] iodide.

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

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 reasonable achievable bearing in mind the need to obtain the intended diagnostic or therapeutic result.

4.5 Interaction with other medicinal products and other forms of interaction

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.

Active substances	Withdrawal period prior to 131 administration of sodium [ I] iodine.
Antithyroid agents (e.g. carbimazole, methimazole, propyluracil), perchlorate	2 - 5 days before until several days after administration.
Salicylates, steroids, sodium nitroprusside, sodium sulfobromophthalein, anticoagulants, antihistamines, antiparasitics, penicillins, sulphonamides, tolbutamide, thiopental	1 week.
Phenylbutazone	1-2 weeks.
Containing iodine expectorants and vitamins	approx. 2 weeks.
Thyroid hormone preparations	2-6 weeks.
Amiodarone*, benzodiazepines, lithium	approx. 4 weeks.
Containing iodine preparations for topical use	1-9 months.
Containing iodine contrast media	up to 1 year.

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

4.6 Pregnancy and lactation

Use during pregnancy:

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.

Use during lactation:

Breast feeding should be discontinued after sodium [ I] iodide administration.

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

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

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The following undesirable effects are recognised for sodium [ I] iodide: Blood and the lymphatic system disorders Bone marrow depression Eye disorders

Sicca syndrome, endocrine ophthalmopathy, acquired dacryostenosis Gastrointestinal disorders Nausea, vomiting Endocrine disorders

Hypothyroidism, aggravated hyperthyroidism, Basedow’s (Graves’) disease, hyperparathyroidism

Infections and infestations

Sialoadenitis

Neoplasms benign, malignant and unspecified (including cysts and polyps) Gastric cancer, leukaemia, bladder and breast cancer

Immune system disorders

Hypersensitivity

Injury, poisoning and procedural complications Radiation thyroiditis

Reproductive system and breast disorders Impairment of fertility in man and woman Congenital, familial and genetic disorders Congenital thyroid disorders.

4.9 Overdose

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.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: diagnostic radiopharmaceuticals, thyroid, sodium iodide (¹³¹I), ATC Code: V09FX03

Pharmacotherapeutic group: therapeutic radiopharmaceuticals, sodium iodide (¹³¹I), ATC Code: V10XA01

Iodide, in the amount used for diagnostic and therapeutic 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.

5.2 Pharmacokinetic properties

Following injection, about 20 % of blood iodide is extracted in a single passage through the thyroid gland. 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.

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.

5.3 Preclinical safety data

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.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium thiosulphate, pentahydrate Sodium dihydrogen phosphate, dihydrate Disodium hydrogen phosphate, dodecahydrate Sodium chloride Sodium hydroxide 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

The shelf-life for this product is 31 days from the activity reference date stated on the label.

6.4 Special precautions for storage

Store below 25^oC. Do not freeze.

Store in original lead container or in equivalent shielding.

6.5 Nature and contents of container

The product is supplied in a Type 1 neutral, clear 10 ml glass vial sealed with a PTFE-faced butyl rubber closure and aluminium overseal.

Each vial is packed within a radiation shielding container of lead metal and placed within a sealed metal tin.

Pack size: 74 MBq - pack sizes range from 37 MBq to 740 MBq

925 MBq - pack sizes range from 925 MBq to 9250 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 00221/0113

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/02/2010

10    DATE OF REVISION OF THE TEXT

25/05/2010

11    DOSIMETRY (IF APPLICABLE)

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.

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 equivalent (EDE) 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 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals, Pergamon Press 1987).

IODIDE

Thyroid blocked, uptake 0%

Iodine-131 half life: 8.02 days

	Absorbed dose per unit activity administered (mGy/MBq)
Organ	Adult	15 Year	10 Year	5 Year	1 Year
Adrenals	3.7E-02	4.2E-02	6.7E-02	1.1E-01	2.0E-01
Bladder wall	6.1E-01	7.5E-01	1.1E+00	1.8E+00	3.4E+00
Bone surfaces	3.2E-02	3.8E-02	6.1 E-02	9.7E-02	1.9E-01
Breast	3.3E-02	3.3E-02	5.2E-02	8.5E-02	1.7E-01
GI tract Stomach wall	3.4E-02	4.0E-02	6.4E-02	1.0E-01	1.9E-01
Small intest	3.8E-02	4.7E-02	7.5E-02	1.2E-01	2.2E-01
ULI wall	3.7E-02	4.5E-02	7.0E-02	1.2E-01	2.1E-01
LLI wall	4.3E-02	5.2E-02	8.2E-02	1.3E-01	2.3E-01
Kidneys	6.5E-02	8.0E-02	1.2E-01	1.7E-01	3.1E-01
Liver	3.3E-02	4.0E-02	6.5E-02	1.0E-01	2.0E-01
Lungs	3.1E-02	3.8E-02	6.0E-02	9.6E-02	1.9E-01
Ovaries	4.2E-02	5.4E-02	8.4E-02	1.3E-01	2.4E-01
Pancreas	3.5E-02	4.3E-02	6.9E-02	1.1E-01	2.1E-01
Red marrow	3.5E-02	4.2E-02	6.5E-02	1.0E-01	1.9E-01
Spleen	3.4E-02	4.0E-02	6.5E-02	1.0E-01	2.0E-01
Testes	3.7E-02	4.5E-02	7.5E-02	1.2E-01	2.3E-01
Thyroid	2.9E-02	3.8E-02	6.3E-02	1.0E-01	2.0E-01
Uterus	5.4 E-02	6.7E-02	1.1E-01	1.7E-01	3.0E-01
Other tissue	3.2E-02	3.9E-02	6.2E-02	1.0E-01	1.9E-01
Effective Dose Equivalent	7.2E-02	8.8E-02	1.4E-01	2.1E-01	4.0E-01
(mSv/MBq)

Bladder wall contributes to 50.8% of the effective dose equivalent.

The effective dose equivalent to an adult administered 3.7MBq with 0% thyroid uptake is 0.27mSv. The effective dose is 0.23mSv.

Incomplete blockage: Effective dose equivalent (mSv/MBq) with little uptake in the thyroid.

uptake: 0.5%	3.0 E-01	4.5 E-01	6.9 E-01	1.5 E+00	2.8 E+00
uptake 1.0%	5.2 E-01	8.1 E-01	1.2 E+00	2.7 E+00	5.3 E+00
uptake 2.0%	9.7 E-01	1.5 E+00	2.4 E+00	5.3 E+00	1.0 E+01

Thyroid uptake 15%

	Absorbed c (mGy/MBq	ose per unit activity administered )
Organ	Adult	15 Year	10 Year	5 Year	1 Year
Adrenals	3.6E-02	4.3E-02	7.1E-02	1.1E-01	2.2 E-01
Bladder wall	5.2E-01	6.4E-01	9.8E-01	1.5E+00	2.9 E+00
Bone surfaces	4.7E-02	6.7E-02	9.4E-02	1.4E-01	2.4 E-01
Breast	4.3E-02	4.3E-02	8.1E-02	1.3E-01	2.5 E-01
GI tract Stomach wall	4.6E-01	5.8E-01	8.4E-01	1.5E+00	2.9E+00
Small intest	2.8E-01	3.5E-01	6.2E-01	1.0E+00	2.0E+00
ULI wall	5.9E-02	6.5E-02	1.0E-01	1.6E-01	2.8E-01
LLI wall	4.2E-02	5.3E-02	8.2E-02	1.3E-01	2.3E-01
Kidneys	6.0E-02	7.5E-02	1.1E-01	1.7E-01	2.9E-01
Liver	3.2E-02	4.1E-02	6.8E-02	1.1E-01	2.2E-01
Lungs	5.3E-02	7.1E-02	1.2E-01	1.9E-01	3.3E-01
Ovaries	4.3E-02	5.9E-02	9.2E-02	1.4E-01	2.6E-01
Pancreas	5.2E-02	6.2E-02	1.0E-01	1.5E-01	2.7E-01
Red marrow	5.4E-02	7.4E-02	9.9E-02	1.4E-01	2.4E-01
Spleen	4.2E-02	5.1E-02	8.1E-02	1.2E-01	2.3E-01
Testes	2.8E-02	3.5E-02	5.8E-02	9.4E-02	1.8E-01
Thyroid	2.1E+02	3.4E+02	5.1E+02	1.1E+03	2.0E+03
Uterus	5.4E-02	6.8E-02	1.1E-01	1.7E-01	3.1E-01
Other tissue	6.5E-02	8.9E-02	1.4E-01	2.2E-01	4.0E-01
Effective Dose Equivalent	6.6E+00	1.0E+-01	1.5E+01	3.4E+01	6.2E+-01
(mSv/MBq)

The effective dose equivalent (EDE) in an adult administered 3.7MBq with 15% thyroid uptake is 24.42mSv.

Thyroid uptake 35%

	Absorbed dose per unit activity administered (mGy/MBq)
Organ	Adult	15 Year	10 Year	5 Year	1 Year
Adrenals	4.2E-02	5.0E-02	8.7E-02	1.4E-01	2.8E-01

Bladder wall	4.0E-01	5.0E-01	7.6E-01	1.2E+00	2.3E+00
Bone surfaces	7.6E-02	1.2E-01	1.6E-01	2.3E-01	3.5E-01
Breast	6.7E-02	6.6E-02	1.3E-01	2.2E-01	4.0E-01
GI tract Stomach wall	4.6E-01	5.9E-01	8.5E-01	1.5E+00	3.0E+00
Small intest	2.8E-01	3.5E-01	6.2E-01	1.0E+00	2.0E+00
ULI wall	5.8E-02	6.5E-02	1.0E-01	1.7E-01	3.0E-01
LLI wall	4.0E-02	5.1E-02	8.0E-02	1.3E-01	2.4E-01
Kidneys	5.6E-02	7.2E-02	1.1E-01	1.7E-01	2.9E-01
Liver	3.7E-02	4.9E-02	8.2E-02	1.4E-01	2.7E-01
Lungs	9.0E-02	1.2E-01	2.1E-01	3.3E-01	5.6E-01
Ovaries	4.2E-02	5.7E-02	9.0E-02	1.4E-01	2.7E-01
Pancreas	5.4E-02	6.9E-02	1.1E-01	1.8E-01	3.2E-01
Red marrow	8.6E-02	1.2E-01	1.6E-01	2.2E-01	3.5E-01
Spleen	4.6E-02	5.9E-02	9.6E-02	1.5E-01	2.8E-01
Testes	2.6E-02	3.2E-02	5.4E-02	8.9E-02	1.8E-01
Thyroid	5.0E+02	7.9E+02	1.2E+03	2.6E+03	4.7E+03
Uterus	5.0E-02	6.3E-02	1.0E-01	1.6E-01	3.0E-01
Other tissue	1.1E-01	1.6E-01	2.6E-01	4.1E-01	7.1E-01
Effective Dose Equivalent	1.5E+01	2.4E+01	3.6E+01	7.8E+01	1.4E+02
(mSv/MBq)

The effective dose equivalent (EDE) in an adult administered 3.7MBq with 35% thyroid uptake is 55.5mSv. The effective dose is 88.8mSv.

Thyroid uptake 55%

	Absorbed dose per unit activity administered (mGy/MBq)
Organ	Adult	15 Year	10 Year	5 Year	1 Year
Adrenals	4.9E-02	5.8E-02	1.1E-01	1.7 E-01	3.4E-01
Bladder wall	2.9E-01	3.6E-01	5.4E-01	8.5 E-01	1.6E-00
Bone surfaces	1.1E-01	1.7E-01	2.2E-01	3.2 E-01	4.8E-01
Breast	9.1E-02	8.9E-02	1.9E-01	3.1 E-01	5.6E-01
GI tract Stomach wall	4.6E-01	5.9E-01	8.6E-01	1.5 E-00	3.0E+00
Small intest	2.8E-01	3.5E-01	6.2E-01	1.0 E+00	2.0E+00
ULI wall	5.8E-02	6.7E-02	1.1E-01	1.8 E-01	3.2E-01
LLI wall	3.9E-02	4.9E-02	7.8E-02	1.3 E-01	2.4E-01
Kidneys	5.1E-02	6.8E-02	1.0E-01	1.7 E-01	2.9E-01
Liver	4.3E-02	5.8E-02	9.7E-02	1.7 E-01	3.3E-01
Lungs	1.3E-01	1.8E-01	3.0E-01	4.8E-01	8.0E-01
Ovaries	4.1E-02	5.6E-02	9.0E-02	1.5E-01	2.7E-01
Pancreas	5.8E-02	7.6E-02	1.3E-01	2.1E-01	3.8E-01
Red marrow	1.2E-01	1.8E-01	2.2E-01	2.9E-01	4.6E-01
Spleen	5.1E-02	6.8E-02	1.1E-01	1.7E-01	3.3E-01
Testes	2.6E-02	3.1E-02	5.2E-02	8.7E-02	1.7E-01
Thyroid	7.9E+02	1.2E+03	1.9E+03	4.1E+03	7.4E+03

Uterus	4.6E-02	6.0E-02	9.9E-02	1.6E-01	3.0E-01
Other tissue	1.6E-01	2.4E-01	3.7E-01	5.9E-01	1.0E+00
Effective Dose Equivalent (mSv/MBq)	2.4E+01	3.7E+01	5.6E+01	1.2E+02	2.2E+02

For this product, the effective dose equivalent (EDE) to an adult with 55% thyroid uptake resulting from the administration of a 3.7MBq capsule is

88.8mSv.

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 organisation (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.