SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

131

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

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

131

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

Reference date	Days after first reference	Activity - MBq (^Ci)
1	0	3.7 (100)
2	7	2.03 (54.9)
3	14	1.11 (30.0)
4	21	0.592 (16.0)
5	28	0.333 (9.0)

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.

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

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Capsule, hard.

White, opaque gelatin capsule.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

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.

4.2 Posology and method of administration

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

1.    For thyroid uptake studies: 0.2-3.7 MBq

2.    For post-thyroid ablation (for metastases and thyroid remnants): 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).

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:

Paediatric dose (MBq) =	Adult dose (MBq) x child weight (kg)
	70 kg
Paediatric dose (MBq) =	2 Adult dose (MBq) x child surface (m )
	1.73 m2

Correction factors given for guidance are proposed below.

Fraction of 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 (EANM)).

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.

•    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 therapeutic administration of sodium [¹³¹I]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 [¹³¹I]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 administration of sodium [131I]iodine.
Antithyroid agents (e.g. carbimazole, methimazole, propyluracil), perchlorate	2-5 days before until several days after administration
Salicylates, steroids, sodium nitroprusside,	1 week

Active substances	Withdrawal period prior to administration of sodium [131I]iodine.
sodium sulfobromophthalein, anticoagulants, antihistamines, antiparasitics, penicillins, sulphonamides, tolbutamide, thiopental
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    Fertility, 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 [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.

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

131

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

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, 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.

5.2 Pharmacokinetic properties

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. 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.

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 Disodium phosphate, dihydrate Sodium hydroxide Water for injections

Capsule

Gelatin

Titanium dioxide (E171)

Sodium laurilsulfate Acetic acid

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 5 weeks from the first activity reference date stated on the label.

6.4    Special precautions for storage

Store below 25°C. Do not freeze.

Store in original lead container or in equivalent shielding.

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.

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 00221/0112

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/02/2010

10    DATE OF REVISION OF THE TEXT

26/09/2014

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%

	Absorbed dose per unit activity administered (mGy/MBq)
Organ	Adult	15 Years	10 Years	5 Years	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	6.1E-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	5.4E-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

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 dose per unit activity administered (mGy/MBq)
Organ	Adult	15 Years	10 Years	5 Years	1 Year
Adrenals	3.6E-02	4.3E-02	7.1E-02	1.1E-01	2.2E-01
Bladder wall	5.2E-01	6.4E-01	9.8E-01	1.5E+00	2.9E+00
Bone surfaces	4.7E-02	6.7E-02	9.4E-02	1.4E-01	2.4E-01
Breast	4.3E-02	4.3E-02	8.1E-02	1.3E-01	2.5E-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 (mSv/MBq)	6.6E+00	1.0E+-01	1.5E+01	3.4E+01	6.2E+-01

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 Years	10 Years	5 Years	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 (mSv/MBq)	1.5E+01	2.4E+01	3.6E+01	7.8E+01	1.4E+02

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 Years	10 Years	5 Years	1 Year
Adrenals	4.9E-02	5.8E-02	1.1E-01	1.7E-01	3.4E-01

Bladder wall	2.9E-01	3.6E-01	5.4E-01	8.5E-01	1.6E-00
Bone surfaces	1.1E-01	1.7E-01	2.2E-01	3.2E-01	4.8E-01
Breast	9.1E-02	8.9E-02	1.9E-01	3.1E-01	5.6E-01
GI tract Stomach wall	4.6E-01	5.9E-01	8.6E-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	6.7E-02	1.1E-01	1.8E-01	3.2E-01
LLI wall	3.9E-02	4.9E-02	7.8E-02	1.3E-01	2.4E-01
Kidneys	5.1E-02	6.8E-02	1.0E-01	1.7E-01	2.9E-01
Liver	4.3E-02	5.8E-02	9.7E-02	1.7E-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.