Stabilised Ceretec 500 micrograms kit for radiopharmaceutical preparation

This medicinal product is for diagnostic use only.

After reconstitution with Sodium Pertechnetate (^99mTc) Injection, the solution of technetium (^99mTc) exametazime is indicated in adults for:

Neurology

Technetium (^99mTc) Exametazime Injection is indicated for use with single photon emission tomography (SPECT). In brain perfusion SPECT, the diagnostic target is detection of abnormalities of regional cerebral blood flow, including:

- Evaluation of patients with cerebrovascular disease (specifically acute stroke, chronic ischaemia and transient ischaemic attack);

- Presurgical lateralisation and localisation of epileptogenic foci;

- Evaluation of patients with suspected dementia (specifically Alzheimer's disease and frontotemporal dementia);

- Adjuvant technique in the diagnosis of brain death

Posology

Adults

555-1110 MBq by direct intravenous injection.

Normally a once-only diagnostic procedure.

Paediatric population

Technetium-99m exametazime with the cobalt chloride solution is not recommended for administration to children. Safety and effectiveness of the cobalt solution has not been established in the paediatric population.

Method of administration

This medicinal product should be reconstituted before administration to the patient.

For instructions on reconstitution of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4

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

Potential for hypersensitivity or anaphylactic reactions

The possibility of hypersensitivity including anaphylactic/anaphylactoid reactions should always be considered. If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

Individual benefit/risk justification

For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.

Renal impairment and hepatic impairment

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

Paediatric population

Paediatric population, see section 4.2

Patient preparation

The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the examination in order to reduce radiation.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol. This should be taken into account in patients on low sodium diet.

Precautions with respect to environmental hazard see section 6.6.

No interaction studies have been performed and no drug interactions have been reported to date.

Women with 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

No data are available on the use of this product in human pregnancy. Animal reproduction studies have not been performed. Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and the foetus.

Breast-feeding

Before administering a radioactive medicinal product to a mother who is breast feeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breast feeding and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk.

If the administration is considered necessary, breast feeding should be interrupted for 12 hours and the expressed feeds discarded.

No studies on the effects on the ability to drive and use machines have been performed.

The frequencies of undesirable effects are defined as follows:

Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data)

¹ Linked with ionising radiation

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose resulting from the administration of a (maximal recommended) activity of 1110 MBq for an adult weighing 70 kg is about 10.3 mSv, these adverse events are expected to occur with a low probability.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

In the event of the administration of a radiation overdose frequent micturition and defecation should be encouraged in order to minimise the absorbed dose to patient.

Pharmacotherapeutic group: diagnostic radiopharmaceutical for central nervous system, technetium (^99mTc),

ATC code: V 09 AA 01

At the chemical concentrations and activities used for diagnostic procedures technetium-99m exametazime does not appear to exert any pharmacodynamic effects.

The technetium-99m complex of the active ingredient is uncharged, lipophilic and of sufficiently low molecular weight to cross the blood-brain barrier. It is rapidly cleared from the blood after intravenous injection. Uptake in the brain reaches a maximum of 3.5-7.0% of the injected dose within one minute of injection. Up to 15% of the cerebral activity washes out of the brain 2 minutes post injection after which there is little loss of activity for the following 24 hours except by physical decay of technetium-99m. The activity not associated with the brain is widely distributed throughout the body particularly in muscle and soft tissue. About 20% of the injected dose is removed by the liver immediately after injection and excreted through the hepatobiliary system. About 40% of the injected dose is excreted through the kidneys and urine over the 48 hours after injection resulting in a reduction in general muscle and soft tissue background.

In vitro stabilisation of technetium-99m exametazime injection with cobalt (II) chloride does not appear to affect the in vivo pharmacokinetics of the complex.

There are no additional preclinical safety data of relevance concerning exametazime for the prescriber in recognising the safety profile of the product used for the authorised indication.

There are no indications that the gross toxicity profile of the stabilised formulation of technetium-99m exametazime is significantly different from that of the non-stabilised formulation.

In vitro mutagenicity studies indicate that the stabilised formulation of technetium-99m exametazime is weakly mutagenic in the Ames (bacterial mutation) test, human lymphocyte chromosome aberration assay and mouse lymphoma thymidine kinase assay. The stabilised formulation is found not to be mutagenic in two in vivo assays (rat bone marrow micronucleus and rat liver micronucleus).

At quantities such as those encountered in stabilised technetium-99m exametazime preparations, cobalt (II) ions or complexed forms of cobalt have no known adverse effects and are rapidly eliminated from the circulation by urinary excretion.

The finished product contains the following excipients:

Ceretec component:

• Sodium chloride Ph. Eur.

• Stannous chloride dihydrate Ph. Eur.

Cobalt stabiliser solution:

• Cobalt (II) chloride 6-hydrate

• Water for injections Ph. Eur.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.

52 weeks from the day of manufacture. The stabilised product must be injected between 30 minutes and 5 hours after preparation.

The stabilised reconstituted product should be stored below 25° C. Do not freeze.

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

Storage should be in accordance with national regulations for radioactive materials.

The freeze-dried component of the product is supplied in a glass vial sealed with a chlorobutyl rubber closure and aluminium overseal and blue flip off cap. The cobalt stabiliser solution is supplied in a glass vial with a chlorobutyl rubber closure and metal overseal.

Pack sizes: each kit contains 2 or 5 vials.

Not all pack sizes may be marketed.

General warning

Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent official organisation.

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

Contents of the vial are intended only for use in the preparation of technetium (^99mTc) exametazime injection and are not to be administered directly to the patient without first undergoing the preparative procedure.

For instructions on reconstitution of the medicinal product before administration, see section 12.

If at any time in the preparation of this product the integrity of this 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.

The content of the kit before reconstitution is not radioactive. However, after sodium pertechnetate (^99mTc), Ph. Eur. is added, adequate shielding of the final preparation must be maintained.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting etc. Radiation protection precautions in accordance with national regulations must therefore be taken.

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 local requirements.