•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

In this leaflet:

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

Sodium [¹³¹I] Iodide

(called Sodium Iodide Injection in this

leaflet)

1.    What Sodium Iodide Injection is and what it is used for

2.    Before you are given Sodium Iodide Injection

3.    How Sodium Iodide Injection is given

4.    Possible side effects

5.    How to store Sodium Iodide Injection

6.    Further information

1. What Sodium Iodide Injection is and what it is used for

This medicine is for diagnostic and therapeutic use. It is used both to help identify illness and treat illness.

Sodium Iodide Injection is a 'radiopharmaceutical' medicine.

•    It contains an active ingredient called 'sodium iodide'.

•    Once injected it can be seen from outside your body by a special camera used in the scan.

•    The scan can help your doctor see tumours in the thyroid glands, and to see how well a tumour is responding to treatment or if the tumour has spread to other parts of the body.

• Some other people are given this medicine to treat a thyroid tumour, an overactive thyroid or to treat goitre (swelling due to an enlarged thyroid).

Your doctor or nurse will tell you anything else you need to know about how Sodium Iodide Injection works.

The use of Sodium Iodide Injection for treatment of an illness is often combined with surgical treatment and with medicines that inhibit the thyroid (antithyroidal agents).

2. Before you are given Sodium Iodide Injection

You should not be given Sodium Iodide Injection:

•    If you are allergic (hypersensitive) to the active ingredient or any other ingredient (listed in Section 6).

•    If you are pregnant or think you might be pregnant.

•    For a scan of benign thyroid tumours.

Do not have Sodium Iodide Injection if any of the above apply to you. If you are not sure talk to your doctor or nurse.

Take special care with Sodium Iodide Injection

Check with your doctor or nurse before having Sodium Iodide Injection:

•    If the person who will be given this medicine is a child or adolescent.

•    If you have missed your last period.

•    If you are breast-feeding.

•    If you are on a low sodium diet.

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This includes herbal medicines. This is because some medicines can affect

the way Sodium Iodide Injection works.

Before you are given Sodium Iodide Injection tell your doctor or nurse if you are taking any of the types of medicine below.

•    Medicines used for an overactive or underactive thyroid such as carbimazole, propylthiouracil, levothyroxine sodium, sodium liothyronine or thyroid extract.

•    'Salicylates'such as aspirin.

•    Steroids such as prednisolone or methylprednisolone.

•    Medicines used to thin the blood such as warfarin or heparin.

•    Antihistamines such as chlorpheniramine or cetirizine.

Medicines used for parasite infections such as thiabendazole, rifampicin or amphotericin B.

Penicillins.

Medicines called 'sulphonamides' such as sulphasalazine (used for rheumatoid arthritis and some bowel problems), sumitriptan (used for migraine) or probenecid (used for gout). Medicines called 'benzodiazepines', which are sedatives or are used to help you sleep, such as temazepam, nitrazepam or diazepam. 'Expectorants', used in cough and cold remedies, such as guaifenesin.

Vitamins.

Lithium, used for mental health problems.

Tolbutamide, used for diabetics. Thiopental, an anaesthetic used in hospital. Phenylbutazone, used for pain and arthritis.

Amiodarone, used for an uneven heart beat.

Liquids or ointments that contain iodine.

Sodium nitroprusside, used in hospital to lower blood pressure.

Sodium sulfobromophthalein, used in hospital to check how well your liver is working. Perchlorate, a medicine given before certain types of scan.

•    Medicines used in hospital for x-rays or scans of the gallbladder.

•    Medicines that contain iodine used in hospitals for x-rays or scans.

If you are not sure if any of the above apply to you, talk to your doctor or nurse before having Sodium Iodide Injection.

Having Sodium Iodide Injection with food and drink

•    Your doctor may recommend a low iodine diet.

•    After been given Sodium Iodide Injection you may be asked to drink more liquids.

Pregnancy and breast-feeding

You should not be given Sodium Iodide Injection if you are pregnant or think that you may be pregnant. This is because it may affect the baby.

You may be told by your doctor not to become pregnant for at least 6 months after being given Sodium Iodide Injection.

Do not breast-feed if you are given Sodium Iodide Injection. This is because small amounts of 'radioactivity' will pass into the mother's milk. If you are breastfeeding, your doctor may wait until you have finished breast-feeding before giving you Sodium Iodide Injection. If it is not possible to wait your doctor will ask you to:

•    stop breast-feeding, and

•    use formula feed for your child, and

•    express (remove) breast milk and throw away the milk.

Your doctor will let you know when you can start breast-feeding again.

Driving and using machines

Ask your doctor if you can drive or use machines after you have been given Sodium Iodide Injection.

Important information Sodium Iodide Injection

When Sodium Iodide Injection is used you are exposed to radioactivity.

• Your doctor will always consider the possible risks and benefits before you are given the medicine.

Ask your doctor if you have any questions.

3. How Sodium Iodide Injection is given

•    Sodium Iodide Injection will always be used in a hospital or clinic.

•    They will tell you anything you need to know for its safe use.

Your doctor will decide the dose that

is best for you.

The usual dose is:

•    One single injection before a scan. Scans may be taken after 4 hrs and up to 72 hrs after injection.

•    The number of doses and length of treatment will depend on your condition.

Ask your doctor if you have any

questions.

Sodium Iodide Injection will be given to you by a specially trained and qualified person.

4. Possible side effects

Like all medicines, Sodium Iodide Injection can cause side effects, although not everybody gets them. The side effects will depend on whether you are being given this medicine to scan (diagnose) or treat a condition. Side effects from Sodium Iodide Injection may occur soon after receiving the product (early side effects) or some time after receiving the product (late side effects). You are only at risk of the late side effects if you have been given this product to treat a condition.

Early side effects

(within hours, days or weeks):

Allergic reactions

If you have an allergic reaction when you are in hospital or a clinic, tell the

doctor or nurse straightaway. The signs may include:

•    skin rash or itching or flushing

•    swelling of the face

•    difficulty in breathing.

If any of these side effects happen after you leave the hospital or clinic go straight to the casualty of your nearest hospital.

Other early side effects include

•    feeling sick (nausea)

•    being sick (vomiting).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

If you are receiving this product as treatment for a condition you may also experience the following early

side effects that your doctor may

be able to prevent or treat

•    diarrhoea

•    pain around your stomach area (abdominal pain)

•    swelling (inflammation) of your thyroid

•    swelling of your windpipe (trachea), which may cause difficulty in breathing

•    swelling of your saliva glands, which may cause pain, some loss of taste and a dry mouth. Occasionally this can be severe, and cause a permanent loss of taste and dry mouth. This has caused some patients to lose teeth.

•    pain, discomfort and swelling in the thyroid area (your neck).

•    if your thyroid is overactive

(hyperthyroidism) your symptoms may get worse for a short time after being given Sodium Iodide Injection. Symptoms could include increased appetite, palpitations, feeling restless (anxiety), weight loss or sweating.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Late side effects

(within weeks, months or years):

• your thyroid may become underactive (hypothyroidism). Signs may include feeling tired or a loss of energy (lethargy), muscle weakness, cramps, feeling the cold, a slow heart rate, dry flaky skin, hair loss, a deep and husky voice, weight gain.

• your parathyroid may become underactive (hypoparathyroidism). Signs may include 'pins and needles', weakness, muscle spasms, muscle twitches or cramps all over, tingling, vibrating, burning and numbness, trouble concentration, feeling dizzy or irritable, sensitivity to noise, muscles that stop working properly (muscle paralysis) or fits (seizures).

High doses of Sodium Iodide Injection or repeat treatments within 6 months of the first treatment may lead to a reduction in the ability of your bone marrow to make blood cells. This can cause bruising and bleeding problems. In many cases patients recover fully. Very rarely, in severe cases, this may cause death.

Patients who have received Sodium Iodide Injection appear to be more at risk of developing stomach cancer and if high doses have been received, leukaemia. There may also be a small increase in the risk of developing bladder and breast cancers.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

5. How to store Sodium Iodide Injection

Sodium Iodide Injection is kept out of the reach and sight of children.

The product label includes the correct storage conditions and the expiry date for the batch. Hospital staff will ensure that the product is stored and disposed of correctly and not used after the expiry date stated on the label.

6. Further Information

What Sodium Iodide Injection contains

•    The active ingredient is sodium [¹³¹I] iodide. Each ml of Sodium Iodide (¹³¹I) Injection contains 74 MBq (Megabecquerel - the unit in which radioactivity is measured) or

925 MBq of sodium [¹³¹I] iodide at a fixed time.

•    The other ingredients are sodium thiosulphate, disodium hydrogen phosphate, sodium dihydrogen

phosphate, sodium chloride and water for injections.

What Sodium Iodide Injection looks like and contents of the pack

Sodium Iodide Injection is supplied as a single clear glass vial containing a solution for injection.

Marketing Authorisation Holder

GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA United Kingdom

Manufacturer

GE Healthcare Buchler GmbH & Co. KG

Gieselweg 1

D-38110 Braunschweig

Germany

PACKAGE LEAFLET: INFORMATION FOR THE USER

This leaflet was last approved in

01/02/2010.

Marketing Authorisations

UK: PL 00221/0113

GE and the GE Monogram are trademarks of General Electric Company

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

Sodium Iodide (¹³¹I) 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 [¹³¹I] 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. 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 xenon-131.

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 dose 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:

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:

Paediatric dose (MBq) = Adult dose (MBq) x child weight (kg)

70"Rg

Paediatric dose (MBq) = Adult dose (MBq) x child surface (m²)

1.73 m²

•    treatment of Graves' disease, toxic multinodular goitre or autonomous nodules

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

Sodium [¹³¹I] iodide therapy is often combined with surgical intervention and with antithyroid medications.

Correction factors given for guidance are proposed below:

Therapeutic use ^{1 2}

• 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.

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 [¹³¹I] 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.

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.

* 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 [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 or use machines

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

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.

4.8 Undesirable Effects

The following undesirable effects are recognised for sodium [¹³¹I] iodide:

Blood and the lymphatic system disorders Bone marrow depression Eye disorders

Sicca syndrome, endocrine ophthalmopathy, acquired dacryostenosis

Gastrointestinal disorders Nausea, vomiting

4.9 Overdose

High radiation exposure through overdose can be reduced by means of administration of thyroid blok-king 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 [¹³¹I] iodide, ATC Code: V09FX03

Pharmacotherapeutic group: therapeutic radiopharmaceuticals, sodium [¹³¹I] iodide,

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 0.5 mm.

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

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.

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.

Once opened store in refrigerator (2°C-8°C) and use within 8 hours.

Since the product does not contain an antimicrobial preservative and is marketed for multidose use, all doses from a single vial should be taken within a single working day and the product stored at (2°C-8°C) after removal of the first aliquot.

6.4    Special precautions for storage

Store below 25°C. 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.

7    MARKETING AUTHORISATION HOLDER

GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA United Kingdom

8    MARKETING AUTHORISATION NUMBER

PL 00221/0113

9    DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of First Authorisation: 01/02/2010

10 DATE OF REVISION OF THE TEXT

02/2010

6.6 Special precautions for disposal and other handling

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.

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 increases 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 (¹³¹I; 8.02 days) Thyroid blocked, uptake 0%

-

1

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

2

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.