CERETEC 500 MICROGRAMS KIT FOR RADIOPHARMACEUTICAL PREPARATION - Summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Ceretec 500 micrograms kit for radiopharmaceutical preparation

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains exametazime 500 micrograms.

Ceretec is reconstituted with Sodium Pertechnetate (99mTc) Injection (not included in this kit) to prepare Technetium (99mTc) Exametazime Injection.

Excipients with known effect

The product before reconstitution contains sodium: 1.77 mg/vial. 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

Kit for radiopharmaceutical preparation.

A white powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

This medicinal product is for diagnostic use only.

After reconstitution with Sodium Pertechnetate (99mTc) Injection, the product is indicated in adults for:

(1) Technetium (99mTc) Exametazime Injection is indicated for brain scintigraphy. The

product is to be used for the diagnosis of abnormalities of regional cerebral blood flow, such as those occurring following stroke and other cerebrovascular disease, epilepsy, Alzheimer’s disease and other forms of dementia, transient ischaemic attack, migraine and tumours of the brain.

(2) Technetium (99mTc) Exametazime Injection is also indicated for in vitro technetium-

99m leucocyte labelling, the labelled leucocytes subsequently being re-injected and scintigraphy carried out to image the sites of localisation. This procedure may be used in the detection of sites of focal infection (e.g. abdominal abscess), in the investigation of pyrexia of unknown origin and in the evaluation of inflammatory conditions not associated with infection such as inflammatory bowel disease.

4.2 Posology and method of administration

The route of administration is direct intravenous injection for brain scintigraphy studies and intravenous injection of labelled leucocytes post labelling in vitro.

Posology

Adults and the elderly population

1. for brain scintigraphy, 350–500 MBq

2. for in vivo localisation of technetium-99m-labelled leucocytes, 200 MBq

Normally a once-only diagnostic procedure.

Paediatric population

Technetium-99m exametazime and technetium-99m-labelled leucocytes are not recommended for administration to children.

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

4.3 Contraindi­cations

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

4.4 Special warnings and precautions for use

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.

Re-injected Ceretec labelled leucocytes only:

When preparing technetium-99m-labelled leucocytes it is essential that cells are washed free of sedimentation agents before they are re-injected into the patient as materials used in cell separation may cause hypersensitivity reactions.

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 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.

4.5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed and no drug interactions have been reported to date.

4.6 Fertility, pregnancy and lactation

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 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 as to whether the investigation could be reasonably delayed until after the mother has ceased breast-feeding and as to whether the most appropriate choice of radiopharmaceutical has been made, 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.

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

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)

Immune system disorders

Not known: Hypersensitivity including rash, erythema, urticaria, angioedema, pruritus.

Re-injected Ceretec labelled leukocytes only:

Not known: Hypersensitivity including rash, erythema, urticaria, angioedema, pruritus, anaphylactoid reaction or anaphylactoid shoc­k.

Nervous system disorders

Not known: Headache, dizziness, paraesthesia

Vascular disorders

Not known: Flushing

Gastrointestinal disorders

Not known: Nausea, vomiting

General disorders and administration site conditions

Not known: Asthenic conditions (e.g., malaise, fatigue)

Exposure to ionising radiation is linked with cancer induction and a potential for developing hereditary defects. As the effective dose is 5.2 mSv when the maximal recommended activity of 555 MBq is administered, 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

4.9 Overdose

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: diagnostic radiopharmace­uticals, central nervous system, ATC code: V09AA01

Pharmacotherapeutic group: diagnostic radiopharmace­uticals, inflammation and infection detection, ATC code: V09HA02

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

5.2 Pharmacokinetic properties

(i) Direct intravenous injection

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.

(ii) Injection of labelled leucocytes

Technetium-99m-labelled leucocytes distribute between the marginating pools of the liver (within 5 minutes) and spleen (within about 40 minutes), and the circulating pool, (the latter represents approximately 50% of the leucocyte pool). Approximately 37% of the cell associated technetium-99m is recoverable from the circulating pool 40 minutes after injection. Technetium-99m activity is slowly eluted from the cells and is excreted partly by the kidneys and partly via the liver into the gall bladder. This results in increasing amounts of activity being seen in the intestines.

5.3 Preclinical safety data

There is no additional preclinical safety data of relevance for the prescriber in recognising the safety profile of the product used for the authorised indications.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride

Stannous chloride dihydrate

6.2 Incompatibilities

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

6.3 Shelf life

52 weeks from the day of manufacture.

Store the reconstituted product below 25°C. Do not freeze or refrigerate. The labelled product must be injected within 30 minutes of reconstitution.

6.4 Special precautions for storage

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

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

6.5 Nature and contents of container

10ml Type I Ph.Eur., clear, colourless, borosilicate glass vial sealed with a chlorobutyl rubber closure and oversealed with an aluminium overseal with a blue flip off cap.

Pack sizes: kit contains 2 or 5 vials.

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. 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.

7 MARKETING AUTHORISATION HOLDER

GE Healthcare Limited

Pollards Wood

Nightingales Lane

Chalfont St Giles

Buckinghamshire HP8 4SP

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 00221/0126

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

09 October 1995      /      21 March 2006

10 DATE OF REVISION OF THE TEXT

05/05/2020

11

Technetium (99mTc) is produced by means of a (99Mo/99mTc) generator and decays with the emission of gamma radiation with a mean energy of 140 keV and a half-life of 6.02 hours to technetium (99Tc) which, in view of its long half-life of 2.13 × 105 years can be regarded as quasi stable.

(1) Brain scintigraphy

The table below shows the dosimetry as calculated according to the Publication 62 of the ICRP (International Commission on Radiological Protection in Biomedical Research, Pergamon Press 1991) following administration of 99mTc-exametazime to adults.

Effective Dose is 4.7 mSv/500 MBq (70 kg individual).

(2) In vivo localisation of technetium-99m-labelled leucocytes

The table below shows the dosimetry as calculated according to the Publication 80 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmace­uticals, Pergamon Press 1998).

Effective Dose is 2.2 mSv/200 MBq (70 kg individual).