META-IODOBENZYLGUANIDINE (131I) FOR THERAPEUTIC USE 185 - 740 MBQ/ML SOLN FOR INFUSION OR INJECTION - patient leaflet, side effects, dosage

PACKAGE LEAFLET:

Meta-lodobenzylguanidine (131I) for Therapeutic Use

Meta-lodobenzylguanidine ( 131 I) for Therapeutic Use 185–740 MBq/ml solution for infusion or solution for injection [131I]Iobenguane

Meta-lodobenzylguanidine (131I) for Therapeutic Use 185–740 MBq/ml solution for infusion or solution for injection is referred to as MIBG Therapeutic in this leaflet.

Read all of this leaflet carefully before you are given MIBG Therapeutic because it contains important information for you.

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

• – If you have any further questions, ask your nuclear medicine doctor who will supervise the procedure.

• – If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

• 1. What MIBG Therapeutic is and what it is used for

• 2. What you need to know before you are given MIBG Therapeutic

• 3. How MIBG Therapeutic is given

• 4. Possible side effects

• 5. How to store MIBG Therapeutic

• 6. Contents of the pack and other information

  
  

1. what mibg therapeutic is and what it is used for

MIBG Therapeutic is a ‘radiopharmace­utical’ medicine.

• It contains an active ingredient called ‘iobenguane’.
• It can be used to treat tumours of the adrenal or thyroid glands.

Your nuclear medicine doctor will tell you anything else you need to know about how MIBG Therapeutic works.

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

Do not have MIBG Therapeutic if any of the above apply to you. If you are not sure talk to your nuclear medicine doctor.

Premature babies or newborn babies (neonates) must not be given MIBG Therapeutic. (See “Important information about some of the ingredients of MIBG Therapeutic”).

2. what you need to know before you are given mibg therapeutic

MIBG Therapeutic must not be used:

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

Warnings and precautions

Check with your nuclear medicine doctor before having MIBG Therapeutic:

• If you have missed your last period.
• If you are on a low sodium diet.
• If you have kidney problems.

Before administration of MIBG Therapeutic you should:

• Drink plenty of water before the start of the examination in order to urinate as often as possible during the first hours after the study.

Other medicines and MIBG Therapeutic

Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. This is because some medicines can affect the way MIBG Therapeutic works. Before you are given MIBG Therapeutic tell your doctor or nurse if you are taking any of the types of medicine below.

• Medicines to lower your blood pressure, such as reserpine, labetalol or calcium channel blockers (which include diltiazem, nifedipine, verapamil, betanidine, debrisoquine, bretylium and guanethidine).
• Medicines for treating depression, such as the amitriptyline, imipramine, doxepin, amoxepine, loxapine, maprotiline or trazolone.
• Medicines for coughs and colds which include 'sympathomimetic agents’ such as the decongestants phenylephrine, ephedrine or phenylpropano­lamine.
• Cocaine.

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

4

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your nuclear medicine doctor for advice before you are given this medicine. You must inform the nuclear medicine doctor before the administration of MIBG Therapeutic if there is a possibility you might be pregnant, if you have missed your period or if you are breastfeeding. When in doubt, it is important to consult your nuclear medicine doctor who will supervise the procedure.

If you are pregnant:

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

If you are breastfeeding:

Do not breastfeed if you are given MIBG Therapeutic. This is because small amounts of ‘radioactivity’ may pass into the mother’s milk. If you are breastfeeding, your doctor may wait until you have finished breastfeeding before using MIBG Therapeutic. If it is not possible to wait your doctor may ask you to:

• stop breastfeeding, and
• use formula feed for your child, and
• express (remove) breast milk and throw away the milk

Please ask your nuclear medicine doctor when you can resume breastfeeding.

Driving and using machines

Ask your doctor if you can drive or use machines after you have been given MIBG Therapeutic.

Tests you will have with MIBG Therapeutic

• Some people will have their blood pressure and heart beat monitored (using an ‘ECG’ machine) when they are given MIBG Therapeutic.
• You will also be asked to give blood samples for up to a month.

MIBG Therapeutic contains Benzyl alcohol and sodium:

• MIBG Therapeutic contains benzyl alcohol. Benzyl alcohol may cause toxic reactions and allergic reactions in infants and children up to 3 years old.
• This medicinal product contains 3.54 mg sodium per ml. To be taken into consideration by patients on a controlled sodium diet.

Important information about MIBG Therapeutic

When MIBG Therapeutic 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 MIBG Therapeutic is given

There are strict laws on the use, handling and disposal of radiopharmaceutical products. MIBG Therapeutic will only be used in special controlled areas. This product will only be handled and given to you by people who are trained and qualified to use it safely. These persons will take special care for the safe use of this product and will keep you informed of their actions. The nuclear medicine doctor supervising the procedure will decide on the quantity of MIBG Therapeutic to be used in your case. It will be the smallest quantity necessary to get the desired effect.

The quantity to be administered usually recommended for an adult ranges from 3700 to 7400 MBq (megabecquerel, the unit used to express radioactivity).

• Your doctor will tell you to take another medicine 24 to 48 hours before you are given MIBG Therapeutic. You will continue to take this medicine for at least 5 days. This medicine is to stop radioactivity building up in your thyroid gland.
• You will be asked to drink plenty of fluids for at least the first 24 hours.
• Scans may be taken after you have been given MIBG Therapeutic.

The recommended dose is:

• single injection (as an infusion into a vein over a period of one to four hours).

After administration of MIBG Therapeutic

• Avoid any close contact with young children and pregnant women for at least one week following the administration.
• Urinate frequently in order to eliminate the product from your body

If you are given more MIBG Therapeutic than you should

MIBG Therapeutic is given in a hospital or clinic by a specially trained and qualified person. It is unlikely that you will be given too much.

If you have any concerns talk to your doctor or nurse.

4. possible side effects

Like all medicines, MIBG Therapeutic can cause side effects, although not everybody gets them.

You may experience the following side effects:

Very common (may affect more than 1 in 10 people)

• feeling sick (nausea) and being sick (vomiting) within the first 24 hours

Common (may affect up to 1 in 10 people)

• High blood pressure including acute episodes of high blood pressure which might be severe.

Not known (frequency cannot be estimated from the available data)

• suppression of the bone marrow. This can include a decrease in platelets in your blood. Signs of this would be bleeding or bruising more easily than usual.
• side effects associated with your salivary gland (for example, swelling of your saliva glands, which may cause pain, some loss of taste and a dry mouth).
• 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.
• increased risk of infection.
• your bone marrow may reduce the number of blood cells it makes if high doses of MIBG Therapeutic or repeat treatments are given. Signs of this may include anaemia, tiredness, bruising more easily and bleeding for longer.
• increased risk of leukaemia or secondary cancer if high doses have been received.

If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme at. By reporting side effects, you can help provide more information on the safety of this medicine.

5. how to store mibg therapeutic

Keep out of the sight and reach 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 MIBG Therapeutic contains

• The active ingredient is [131I]iobenguane. Each vial of MIBG Therapeutic contains between 185–740 MBq/ml (Megabecquerel -the unit in which radioactivity is measured) of iodine-131 at a fixed time.
• The other ingredients are sodium chloride, benzyl alcohol and water for injections.

What MIBG Therapeutic looks like and contents of the pack

MIBG Therapeutic is supplied as a single colourless glass vial containing a solution for infusion or solution for injection.

Marketing Authorisation Holder

GE Healthcare Limited

Pollards Wood

Nightingales Lane

Chalfont St Giles

Buckinghamshire HP8 4SP

United Kingdom

Manufacturer

GE Healthcare Buchler GmbH & Co. KG

Gieselweg 1

38110 Braunschweig

Germany

This leaflet was last revised in

September 2019

Marketing Authorisation

UK: PL 00221/0125

10

GE and the GE Monogram are trademarks of General Electric Company.

GE Healthcare

HEALTHCARE PROFESSIONAL INFORMATION

PACKAGE LEAFLET:

INFORMATION FOR HEALTHCARE PROFESSIONAL

• 1 NAME OF THE MEDICINAL PRODUCT

Meta-Iodobenzylguanidine (131I) for Therapeutic Use 185–740 MBq/ml solution for infusion or solution for injection

Meta-Iodobenzylguanidine (131I) for Therapeutic Use 185–740 MBq/ml solution for infusion or solution for injection [131I]iobenguane

IBS6712

• 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

[131I]iobenguane 185–740 MBq/ml

(Not more than 0.67 mg/ml)

Summary of the physical characteristics of the radioactive isotope in the active substance: Iodine-131: Physical half-life 8.02 days.

The most important radiation emissions are as below:

Abundance(%)

1.8

7.2

89.7

0.7

82.0

Excipients with known effect

• Benzyl alcohol: 10 mg/ml
• Sodium: 3.54 mg/ml.

For a full list of excipients, see section 6.1.

• 3 PHARMACEUTICAL FORM

Solution for infusion or for solution for injection.

Clear, colourless solution.

• 4 CLINICAL PARTICULARS

  • 4.1 Therapeutic indications

Radiation therapy of tumour-tissue that is capable of retaining iobenguane. These are tumours arising from cells originating embryologically from the neural crest; pheochromocytomas, neuro-blastomas, carcinoids and medullary carcinomas of the thyroid gland (MCT).

• 4.2 Posology and method of administration

Posology

Therapeutic dose with an amount of [131I]iobenguane individually tailored on the basis of a dosimetric study. The size of the dose as well as the interval(s) between possible multiple administrations are mainly determined by haematological radio-toxicity and the kind of tumour. The more rapid the rate of progression of the tumour, the shorter the interval.

The “fixed” therapeutic dose is (3700–7400 MBq).

Elderly population:

No special dosage-scheme is required for the elderly patient.

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 recommended dosages are identical for children and adults. Meta-iodobenzylguanidine (131I) for Therapeutic Use is contraindicated in premature babies and neonates.

Method of administration

This product is for single use only.

The therapeutic dose is administered intravenously, generally as an infusion over a period of 1– 4 hours.

• 4.3 Contraindi­cations

Pregnancy is an absolute contraindication.

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

Must not be given to premature babies or neonates.

• 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 immediately available.

Normal tissue adjacent to the radiated cancer tissue may become damaged (e.g. gonadal dysfunction in patients with pelvic metastases).

Additive toxicity may occur in patients on chemotherapy (e.g. lung fibrosis, hypergonadotropic hypogonadism).

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 therapeutic effect.

Paediatric population

Children treated with [131I]iobenguane are at risk of developing irreversible thyroid function loss, growth retardation and hypergonadotropic hypogonadism.

During follow up it is therefore recommended that special attention is paid to their endocrine status.

This medicinal product contains benzyl alcohol. Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.

Renal impairment

Careful consideration of the benefit risk ratio in these patients is required, since an increased radiation exposure is possible.

Patient Preparation

Drugs that may interfere with uptake and retention of [131I]iobenguane should be stopped before treatment (see section 4.5).

Several drugs used in the treatment of high blood pressure and in psychiatry, interact with [131I]ioben-guane. Concomitant use therefore may interfere with the uptake and retention of [131I]iobenguane and thus influence the radiation dose delivered both to normaland to tumour-tissue. These drugs should be stopped before treatment (usually for four biological half-lives).

Thyroid blockade is started 24–48 hours before the [131I]iobenguane is administered and continued for at least 5 days. Blockade by potassium perchlorate is achieved by administration of approximately 400 mg/day. Blockade by potassium iodide, potassiumiodate or Lugol solution must be performed with an equivalent of 100 mg of iodine/day.

Patients should be encouraged to increase oral fluids and urged to void as often as possible to reduce bladder radiation, especially after high activities e.g. for radionuclide therapy. Patients with bladder voiding problems should be catheterised after administration of therapeutic dose.

[131I]iobenguane therapy should be considered only in those patients where transplantation of autologous bone marrow (containing little or no tumour cells) is possible. The toxic effects on bone marrow (thrombocytopenia) must be monitored carefully and frequently.

Blood counts are to be controlled every 2 days during the first week and later once a week for the month following the last administration.

It is advisable but not mandatory to perform whole body scintigram for about 1 week in order to study the biodistribution of the agent and quantitate the uptake in tumour foci.

Repeated treatments can be considered at 6–8 month intervals. Cumulative doses up to 29600 MBq have been reported; bone marrow toxicity is the limiting factor.

The uptake of iobenguane in the chromaffin granules might, though rarely, cause rapid noradrenalin secretion which can induce a transient hypertensive crisis. This necessitates constant monitoring of the patient during administration. Monitoring of both ECG and blood pressure during administration could be indicated in some patients.

Prior to administration, ensure emergency cardiac antihypertensive treatments are readily available. [131I]iobenguane must be administered slowly.

In patients where the diagnostic evaluation shows diffuse bone marrow uptake of [131I]iobenguane, bone marrow suppression may occur after administration of a therapeutic dose.

When the therapeutic administration for pheochromocytoma is planned attention is to be given to possible interference between the medication for control of hypertension and the uptake of [131I]iobenguane. Incompatible medication should be stopped at least 2 weeks prior to the planned therapeutic administration. If necessary propranolol can be used instead.

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 the product in patients with significant renal impairment requires special attention with regards to administered activity.

Dosages for patients, who have undergone prior treatment with cytostatic drugs (e.g. cisplatinum compounds) resulting in reduced renal function, may have to be adjusted accordingly.

Women receiving [131I]iobenguane should be advised not to become pregnant within at least 6–12 months of administration.

After the procedure

Close contact with infants and pregnant women should be restricted for at least one week after administration of therapeutic doses.

Specific warnings

This medicinal product contains sodium: 3.54 mg/ml. This needs to be taken into consideration for patients on a controlled sodium diet.

Precautions with respect to environmental hazard see section 6.6.

• 4.5 Interaction with other medicinal products and other forms of interaction

The following drugs are known or may be expected to prolong or to reduce the uptake of iobenguane in neural crest tumours. There are additional drugs that may interfere, but no formal proof exists.

• Nifedipine (a Ca-channel blocker) is reported to prolong retention of iobenguane.

Decreased uptake was observed under therapeutic regimens involving the administration of:

• Antihypertensive drugs as reserpine, labetalol, calcium-channel blockers (diltiazem, nifedipine, verapamil).
• Sympathomimetic agents (present in nasal decongestants, such as phenylephrine, ephedrine or phenylpropano­lamine).
• Cocaine.
• Tricyclic antidepressants such as amitriptyline and derivatives, imipramine and derivatives, doxepin, amoxepine and loxapine.

For the following drugs inhibition of the uptake of iobenguane is expected to occur, but no proof is yet available:

• Antihypertensives acting through adrenergic neuron blockade (betanidine, debrisoquine, bretylium and guanethidine).
• Antidepressants such as maprotiline and trazolone.

These drugs should be stopped before treatment (usually for four biological half-lives).

Anti-emetics:

Special care must be given to the selection of anti-emetics that are often given to suppress the nausea that generally accompanies the administration of iobenguane in therapeutic quantities. Anti-emetics that are dopamine/serotonin receptor antagonists do not interfere with iobenguane uptake at concentrations as are used in clinical practice.

• 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:

The use of [131I]iobenguane is contraindicated in pregnant women because radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus (see section 4.3).

When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise.

Breastfeeding:

Before administering a radiopharmaceutical to a mother who is breast feeding, consideration should be given as to the possibility of delaying the administration until the mother has ceased breast feeding.

Breast-feeding should be discontinued after administration of the product and the expressed feeds discarded.

• 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

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases it is necessary to ensure that the risks of the radiation are less than from the disease itself. The effective dose is 1.11 Sv when the maximal recommended activity of 7400 MBq is administered.

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).

Infections and infestations

Not known: Infection susceptibility increased.

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Not known: Leukaemias, malignant secondary cancers.

Blood and lymphatic system disorders

Not known: Bone marrow depression, anaemia, thrombocytopenia, neutropenia.

Vascular disorders

Common: Hypertension including acute episodes of hypertensive crisis (observed with the therapeutic use of [131I] iobenguane).

Endocrine disorders

Not known: Hypothyroidism, possibly leading to growth retardation in children. Hyperthyroidism.

Gastrointestinal disorders

Very common: Nausea, vomiting.

Not known: Salivary gland conditions.

Injury, poisoning and procedural complications

Not known: Radiation injury (including radiation associated pain, interstitial lung disease, transient sialoadenitis, hypogonadism, ovarian failure).

Paediatric Population

The main adverse reactions in children are thrombocytopenia (isolated) or bone marrow suppression, the more so if there is tumour infiltration in bone marrow. Adverse reactions related to the function of the salivary glands or of the myocardium, or toxic effects on the liver have not been described.

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

• 4.9 Overdose

The effect of an overdose of iobenguane is due to the release of adrenaline. This effect is of short duration and requires supportive measures aimed at lowering the blood pressure. Prompt injection of a rapid acting alpha-adrenergic blocking agent (phentolamine) followed by a beta-blocker (propranolol). Because of the renal elimination pathway maintaining the highest possible urine flow is essential to reduce the absorbed dose to the patient.

• 5 PHARMACOLOGICAL PROPERTIES

  • 5.1 Pharmacody­namic properties

Pharmacotherapeutic group: therapeutic radiopharmace­uticals, other therapeutic radiopharmace­uticals, iobenguane (131I), ATC code V10XAA02.

Mechanism of action

[131I]iobenguane is a radioiodinated aralkylguanidine. Its structure contains the guanidine-group from guanethidine linked to a benzyl-group into which iodine is introduced. Like guanethidine, the aralkylguanidines are adrenergic neuron blocking agents. As consequence of a functional similarity between adrenergic neurons and the chromaffin cells of the adrenal medulla, iobenguane is able to localise preferentially in the medulla of the adrenal glands. In addition, localisation in the myocardium occurs.

Pharmacodynamic effects

Of the various aralkylguanidines iobenguane is the preferred substance because of its low liver uptake and its best in vivo stability, resulting in the lowest achievable uptake of liberated iodide by the thyroid. Transport of iobenguane across the cell membranes of cells originating from the neural crest is an active process when the concentration of the drug is low (as in diagnostic dosages). The uptake mechanism can be inhibited by uptake of inhibitors such as cocaine or desmethylimipra­mine. When the drug is administered in higher concentrations (as in therapeutic dosages) passive diffusion processes become also important. The clinical implications towards dosimetry, if any, are unclear.

Subsequently, an active mechanism transfers at least part of the intracellular iobenguane into the storage granules within the cells.

• 5.2 Pharmacoki­netic properties

Distribution and Organ uptake

The distribution pattern of iobenguane includes rapid initial uptake in liver (33% of the administered dose) and much less in lungs (3%), myocardium (0.8%), spleen (0.6%) and salivary glands (0.4%). Uptake in normal adrenals (adrenal medulla) is so low that these cannot be visualised with [131I]iobenguane. Hyperplastic adrenals show a high uptake.

Elimination

Iobenguane is to a large extent excreted unaltered by the kidneys. 70 to 90% of administered doses are recovered in urine within 4 days. The following metabolic breakdown products were recovered in urine: iodide-131, [131I]-metaiodohippuric acid, [131I]-hydroxy-iodobenzylguanidine and [131I]-metaiodobenzoic acid. These substances account for approximately 5 to 15% of the administered dose.

8

Half-life

Iodine-131 [131I] is a beta-emitting radionuclide with a physical half-life of 8.02 days.

Whole body retention can be described by a biexponential with half-lives of 3 hours (36%) and 1.4 days (63%). 1% is retained in the liver with a long half-life relative to the I-131 physical half-life. Thyroid blocking is assumed.

Renal/Hepatic impairment

The pharmacokinetics in patients with renal or hepatic impairment has not been characterised.

• 5.3 Preclinical safety data

In dogs 20 mg/kg is a lethal dose. Lower dose levels (14mg/kg) cause transient clinical signs of toxic effect. Repeated intravenous administrations in rats of 20 to 40 mg/kg induce signs of serious clinical toxicity. Repeated intravenous administrations of 5 to 20 mg/kg do induce effects, including respiratory distress, but long term effects are only a slight increase in weight of liver and heart. Repeated administration in dogs of 2.5 to 10 mg/kg do induce clinical effects, including increased blood pressure and abnormalities in heart rate and in cardiac pulse propagation, but all signs were of a transient nature.

The margin of safety between administered amounts of iobenguane (notably in therapeutic doses) and the level at which unwanted secondary effects might occur is not very wide, therefore patients should be kept under close surveillance during and for at least some hours after the infusion or injection of the drug.

In the test systems used no mutagenic effect could be demonstrated. Studies of carcinogenic potential of iobenguane have not been published.

• 6 PHARMACEUTICAL PARTICULARS

  • 6.1 List of excipients

Benzyl alcohol

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

The shelf-life is 2 days from the activity reference date stated on the label.

Diluted: Use within 2 hours of dilution.

• 6.4 Special precautions for storage

The product should be stored in dry ice (solid carbon dioxide) until approximately one hour before use.

About 1 hour prior to administration the vial contained within its lead shield should be thawed by placing it in a water bath not exceeding 50°C.

For storage conditions after dilution of the medicinal product, see section 6.3.

Store in original lead container or in equivalent shielding.

• 6.5 Nature and contents of container

The product is supplied in a clear neutral 10 ml glass vial sealed with a PTFE-faced butyl rubber closure.

Pack sizes: single vials containing 370 to 3700 MBq in 185 MBq steps

Not all pack sizes may be marketed.

• 6.6 Special precautions for disposal and other handling

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 licenses 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.

For instructions on dilution of the medicinal product before administration, see sections 12.

The administration of the radiopharmace­uticals creates risks to other persons, from external radiation or contamination from spills or urine, vomiting, etc.

Radiation protection precautions in accordance with national regulations must therefore be taken.

9

If at any time in the preparation of this product the integrity of the vial is compromised it should not be used.

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.

This preparation is likely to result in relatively high radiation dose to most patients. The administration of Meta-Iodobenzylguanidine (131I) for Therapeutic Use may result in significant environmental hazard. This may be of concern to the immediate family of patients or the general public. Suitable precautions in accordance with national regulations should be taken concerning the activity eliminated from patients, in order to avoid any contamination.

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

UK: PL 00221/0125

9 DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

	Date of first authorisation	Date of last renewal
UK	14 February 1997	15 February 2002

• 10 DATE OF REVISION OF THE TEXT

September 2019

• 11 DOSIMETRY

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).

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. This should be taken into consideration when using the following information. With the exception of “uterus” the list includes only those organs which are used in the calculation for the effective (whole body) dose equivalent. These are the seven standard organs and the additional five organs with the highest absorbed dose (marked with *).

Organ		Absorbed dose
	per unit activity administered (mGy/MBq)
	Adult	15 year	10 year	5 year	1 year
Bone surfaces	6.1E-02	7.2E-02	1.1E-01	1.8E-01	3.6E-01
Breast	6.9E-02	6.9E-02	1.1E-01	1.8E-01	3.5E-01
Kidneys	1.2E-01	1.4E-01	2.1E-01	3.0E-01	5.1E-01
Lungs Gonads	1.9E-01	2.8E-01	3.9E-01	6.0E-01	1.2E+00
Ovaries	6.6E-02	8.8E-02	1.4E-01	2.3E-01	4.2E-01
Testes	5.9E-02	7.0E-02	1.1E-02	1.9E-01	3.6E-01
Red marrow	6.7E-02	8.3E-02	1.3E-01	1.9E-01	3.5E-01
Thyroid	5.0E-02	6.5E-02	1.1E-01	1.8E-01	3.5E-01
*Adrenals	1.7E-01	2.3E-01	3.3E-01	4.5E-01	6.9E-01
*Bladder wall	5.9E-01	7.3E-01	1.1E+00	1.7E+00	3.3E+00
*Liver	8.3E-01	1.1E+00	1.6E+00	2.4E+00	4.6E+00
*Salivary glands	2.3E-01	2.8E-01	3.8E-01	5.1E-01	7.5E-01
*Spleen	4.9E-01	6.9E-01	1.1E+00	1.7E+00	3.2E+00
Uterus	8.0E-02	1.0E-01	1.6E-01	2.6E-01	4.8E-01
Effective dose equivalent (mSv/MBq)	2.0E-01	2.6E-01	4.0E-01	6.1E-01	1.1E+00

The above data are valid in normal pharmacokinetic behaviour. Especially when renal function is impaired, due to disease or due to previous therapy, the effective dose equivalent and the radiation dose delivered to organs (notably to bone, red marrow and lungs) might be increased considerably.

• 12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACE­UTICALS

Withdrawals should be performed under aseptic conditions. The vials must not be opened before disinfecting the stopper, the solution should be withdrawn via the stopper using a single dose sgringe fitted with suitable protective shielding and a disposable sterile needle or using an authorised automated application sgstem. If the integritg of this vial is compromised, the product should not be used.

About 1 hour prior to administration the vial contained within its lead shield should be thawed bg placing it in a water bath not exceeding 50°C. It is recommended that the dose be diluted with 50 ml sterile phgsiological saline for infusion on thawing and immediatelg prior to administration bg intravenous infusion.

For storage conditions after dilution of the medicinal product, see section 6.3.

• 13 OTHER INFORMATION