Consumer medicine information

What is in this leaflet?

This leaflet answers some common questions about CERETEC. It does not contain all the available information, nor does it take the place of talking to your doctor or treatment provider.

All medicines and diagnostic preparations have risks and benefits. Your doctor has weighed the risks of you being treated with CERETEC against the expected benefits.

If you have any concerns about being given this preparation, ask your doctor, or treatment provider.

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

What CERETEC is used for

CERETEC is used in the preparation of a radiopharmaceutical which is a medicinal product containing a small amount of radioactivity.

Such radiopharmaceuticals are given in small amounts to find or rule out a disease. The radiation your body receives is very low and is considered safe. After the radioactive liquid is given to you, it is taken up by the organs of interest or just passes through your body. The radiation is taken up by a special camera and pictures are prepared. These pictures allow the nuclear medicine doctor to detect any problems.

In particular, CERETEC is used to produce images of the brain of patients who have fits or seizures. They occur when the brain's electrical currents become disordered from time to time in some people. This disease is called epilepsy. There is a number of different types of epilepsy. CERETEC is used particularly for the imaging of patients with epilepsy which originates in the parts of the brain just centre and slightly behind the ears.

CERETEC is used to help find or rule out a diagnosis only. It is not used to treat or cure epilepsy.

Your doctor may have prescribed CERETEC for another reason.

CERETEC is not recommended normally for use in children because studies have not been performed on the use of CERETEC in children. Nevertheless, your doctor may have decided to still use it and will have weighed up the risks and benefits.

Ask your doctor if you have any questions about why CERETEC has been prescribed for you.

Before you are given CERETEC

When you must not be given it

You must not be given CERETEC if you are allergic to it, or:

• any of the ingredients listed at the end of this leaflet or,
• have had a previous allergic reaction in a diagnostic procedure with the same or similar preparation.

Before you are given CERETEC

Your doctor must know about all of the following before you are given CERETEC. Tell your doctor if you:

1. have allergies to:

• any other medicines, particularly those containing technetium or other imaging agents
• any other substances, such as foods, preservatives (substances to maintain food quality or freshness) or dyes (colourants)
• any of the ingredients of CERETEC listed at the end of this leaflet or to technetium (as CERETEC will be made up in a solution of Technetium and sodium chloride for injection).

2. are pregnant or intend to become pregnant in the near future.

CERETEC is to be avoided during pregnancy as adequate testing has not been performed. Your doctor may decide that the benefit may outweigh the risk. Radiopharmaceuticals are not usually given to pregnant women to avoid exposing the foetus to radiation. However, some radiopharmaceuticals may be used for diagnostic tests in pregnant women, so it is important to inform your doctor if you are pregnant.

3. are breastfeeding.

Components of CERETEC may be excreted in the breast milk. Therefore, you should stop breastfeeding and substitute formula feeds for at least 24 hours after you are given CERETEC or longer if your doctor tells you to.

4. have, or have had any other medical conditions.
5. you plan to have surgery.

If you have not told your doctor about any of the above, tell them before you are given CERETEC.

Taking other medicines

Tell your doctor if you are taking any other medicines including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor or treatment provider has more information on medicines to be careful with or to avoid when you are given CERETEC.

If you have not told your doctor about any of the above, tell them before you are given any CERETEC.

How CERETEC is given

Your doctor may have special instructions for you to follow to get ready for your procedure.

CERETEC is given as an injection into a vein. CERETEC must only be given by a doctor or nuclear medicine technologist.

Your doctor is qualified in nuclear medicine and will decide what dose of CERETEC you will receive, depending on your condition and other factors, such as your weight. In any case, the amount of radioactivity in the injection will not be big.

CERETEC is usually given as a single dose and within minutes after it is given diagnostic images will be taken.

If you have any questions about taking CERETEC or about the diagnostic procedure, ask your doctor.

After being given CERETEC

CERETEC breaks down quickly after it is given and is virtually removed from the body after about 48 hours.

After completion of the examination, however, the doctor may ask you to go to the toilet to reduce the radiation dose to your bladder and the surrounding organs. You may also be asked to drink water to help with this process.

If you have any questions or concerns, be sure to discuss these with your doctor.

Side Effects

The following side effects have been reported after use of CERETEC:

• rash
• symptoms of allergy/sensitivity
• red skin
• swelling of the face
• fever
• brief increase in blood pressure

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Do not be alarmed by this list of side effects. You may not experience any of them.

Overdose

The dose of CERETEC you will receive will be calculated by a qualified nuclear medicine doctor and given to you in a highly specialised setting. Therefore the possibility of overdose is minimal.

Storage

CERETEC will be stored by the hospital or clinic.

The hospital or clinic will make sure that CERETEC is not used if the expiry date (EXP) printed on the pack has passed.

Further information

This is not all the information that is available on CERETEC. If you have any more questions or are not sure about anything, ask your doctor or nuclear medicine technologist.

Product description

Ingredients

Each vial contains:

active ingredient -
exametazime 0.5mg

other ingredients -
sodium chloride
stannous chloride dihydrate
nitrogen gas in the headspace

Australian Registration Number: AUST R 10018

Sponsor

CERETEC is made in England and supplied in Australia by:

GE Healthcare Australia Pty Ltd
ABN 32 001 408 402
241 O’Riordan St
Mascot NSW 2020

Tel 1300 887 764
Fax 1300 434 232

This leaflet was prepared in March 2024

Ceretec is a trademark of GE HealthCare

GE is a trademark of General Electric Company, used under trademark license.

Published by MIMS April 2024

1 Name of Medicine

Exametazime.

2 Qualitative and Quantitative Composition

The Ceretec kit is supplied as packs of two or five single dose vial units for use in the preparation of a technetium [^99mTc]-exametazime intravenous injection. Each single dose vial unit contains a pre-dispensed sterile, non-pyrogenic, lyophilized mixture of 0.5 mg exametazime [(RR,SS)-4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime], 7.6 microgram stannous chloride dihydrate (minimum stannous tin 0.6 microgram; maximum total stannous and stannic tin 4.4 microgram per vial) and 4.5 mg sodium chloride, sealed under nitrogen atmosphere at a pressure just below atmospheric, with a rubber closure. The product contains no antimicrobial preservative.

Physical characteristics.

External radiation.

3 Pharmaceutical Form

See Section 2 Qualitative and Quantitative Composition.

4 Clinical Particulars

4.1 Therapeutic Indications

Technetium [^99mTc]-exametazime scintigraphy is indicated for scintigraphic localisation of seizure foci in patients with temporal lobe epilepsy in institutions with appropriate expertise and facilities.

4.2 Dose and Method of Administration

Administration is by intravenous injection for diagnostic use.
Normally a once-only diagnostic procedure.
Normal safety precautions for the handling of radioactive materials should be observed in addition to the use of aseptic technique to maintain sterility of the vial contents.
The user should wear waterproof gloves and use shielding at all times when handling the vial and syringes.
The recommended dose range for i.v. administration, after reconstitution with sodium pertechnetate [^99mTc], to be used in the average adult (70 kg) is 350-500 MBq.
Do not use the final radiopharmaceutical preparation more than 30 minutes after the time of reconstitution. Dispose of any unused material (and its container) via an authorised route.
Dynamic imaging may be performed between 0 to 10 minutes following injection. Static imaging may be performed from 15 minutes up to 6 hours after injection.
Although gross abnormalities may be visualised by planar imaging, it is strongly recommended that SPECT imaging is carried out to maximise the value of the study.

Radiation dosimetry.

Procedure for the preparation of technetium [^99mTc] exametazime injection.

Cautionary notes.

Quality control.

Interpretation of chromatograms.

4.3 Contraindications

None known.

4.4 Special Warnings and Precautions for Use

Also see Section 6.2 Incompatibilities.
As part of the manufacture, the vial of freeze-dried product is filled with an inert nitrogen atmosphere to a pressure just below atmospheric before being sealed with the rubber closure. The product does not contain an antimicrobial preservative. Technetium [^99mTc]-exametazime should not be mixed with any substance other than those recommended for reconstitution.
This product is a component for use in the preparation of a radioactive product intended for pharmaceutical use. Because of the small mass of chemical substances present, there is negligible risk to persons handling or administering the material, other than that from the radioactive nature of the reconstituted product.
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 reasonably achievable bearing in mind the need to obtain the intended diagnostic result. Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. For diagnostic nuclear medicine investigations the current evidence suggests that these adverse effects will occur with negligible frequency because of the low radiation dose incurred.
For most diagnostic investigations involving a nuclear medicine procedure, the effective dose (E) to the patient is less than 20 mSv. The activity administered must not be greater than is necessary to provide the intended diagnostic information.
The use of [^99mTc]-exametazime and the interpretation of images in patients with temporal lobe epilepsy requires considerable experience. In order to avoid false positive interpretations, the findings of [^99mTc]-exametazime scintigraphy may be accepted if concordant with EEG and neurophysiological assessment. [^99mTc]-exametazime scintigraphy findings should not over-ride apparently discrepant EEG results. EEG should be continuously monitored immediately prior to and during injection of the radiopharmaceutical.
In the event of scintigraphy being performed in close proximity to a seizure, it is essential to record injection time in relation to the cessation of the fit for accurate interpretation of the study.
Each dose vial is expressly intended for single patient use. Any deviation from the Ceretec intended usage, including the preparation of multiple doses from the single dose vial supplied, may result in misdiagnosis.
The contents of the Ceretec vial are not radioactive. However, after the sodium pertechnetate [^99mTc] is added, adequate shielding of the final preparation must be maintained.
The contents of the Ceretec vial are intended only for use in preparation of technetium [^99mTc]-exametazime injection and are not to be administered directly to the patient.
A thorough knowledge of the normal distribution of intravenously administered technetium [^99mTc]-exametazime injection is essential in order to interpret pathologic studies accurately.
The contents of the Ceretec vial are sterile and pyrogen free. The vial contains no antimicrobial preservative. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures which comply with the requirements of Good Manufacturing Practice for Pharmaceuticals, during preparation of the radiopharmaceutical.
Technetium [^99mTc]-exametazime injection, like other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimise radiation exposure to clinical personnel. Care should also be taken to minimise radiation exposure to the patient consistent with proper patient management. Radiopharmaceuticals should be used only by or under the control of physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate governmental agency authorised to license the use of radionuclides.
To minimise radiation dose to the bladder, the patient should be encouraged to void when the examination is completed and as often, thereafter, as possible. Adequate hydration should be encouraged to permit frequent voiding.
The disposal of all radioactive wastes should be carried out in accordance with the NH and MRC "Code of Practice for the Disposal of Radioactive Wastes by the User (1985)".

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No drug interactions have been reported to date. Also see Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of it's registration.

4.8 Adverse Effects (Undesirable Effects)

A very few cases of mild hypersensitivity evidenced by the development of an urticarial rash with generalised erythema, facial oedema and fever has been reported. A transient increase in blood pressure was seen in 8% of patients. A very few cases have also been reported of possible vascular spasm following administration of the reconstituted product.
In case of side effects following administration of radiopharmaceuticals, users should ensure the availability of appropriate medical treatment at the time of administration of any radiopharmaceutical to the patient.

Reporting suspected adverse effects.

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 the patient.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

When sodium pertechnetate [^99mTc] is added to exametazime in the presence of stannous reductant, a lipophilic technetium-99m complex is formed. This lipophilic complex is the active moiety. It converts with time to a secondary complex which is less lipophilic. When the secondary complex is isolated from the lipophilic species, it has been shown to be unable to cross the blood-brain barrier. A consequence of the conversion of lipophilic to secondary complex is that the useful life of the reconstituted agent is restricted to 30 minutes.
Studies in normal volunteers have shown that the technetium-99m complex of the RR,SS(d,l) diastereoisomer of exametazime is rapidly cleared from the blood after intravenous injection. Blood activity falls to 15%, 10% and 4% of the administered dose at 5 minutes, 1 hour and 24 hours respectively. 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 activity is eliminated from the brain by 2 minutes post injection, after which little activity is lost 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 30% of the injected dose is found in the gastrointestinal tract immediately after injection and about 50% of this is excreted through the intestinal tract over 48 hours. 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.

5.3 Preclinical Safety Data

Acute toxicity studies have been performed on intravenously administered Ceretec in male and female rats and rabbits. No adverse reactions or mortality were observed at a dose equivalent to the single injection of 1200 times the maximum human equivalent dose. Fourteen day repeat-dose studies in rats and rabbits at a cumulative dose of up to 14,000 times the maximum human equivalent dose did not reveal adverse reactions, abnormalities, or mortality. At termination, histopathology, haematology and blood chemistry revealed no abnormalities.

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
The technetium [^99mTc] labelling reaction involved in preparing technetium [^99mTc]-exametazime injection depends on maintaining tin in the divalent (reduced) state. Any oxidant present in the sodium pertechnetate [^99mTc] employed may adversely affect the quality of the preparation. Sodium pertechnetate [^99mTc] containing oxidants should not be used for the preparation of the labelled product. To meet the last requirement, a generator must be eluted within 24 hours prior to obtaining any eluate for reconstitution with the Ceretec kit. The eluate for reconstitution should not have been eluted more than two hours prior to use.
Sodium Chloride Injection BP must be used as the diluent. Do not use bacteriostatic sodium chloride as a diluent for sodium pertechnetate [^99mTc] injection because it will increase the oxidation products and adversely affect the biological distribution of Ceretec.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging and will normally be not less than 10 weeks after the date of dispatch. The product must not be used after the expiry date.

6.4 Special Precautions for Storage

Store below 25°C. Do not freeze.
Store the reconstituted injection at 15°C-25°C and use within 30 minutes following reconstitution.

6.5 Nature and Contents of Container

The product is supplied as pack of 2 or 5 single dose units for the preparation of [^99mTc]-exametazime intravenous injection. Each unit comprises a type I clear glass vial containing pre-dispensed, sterile, non-pyrogenic, freeze-dried ingredients with rubber stopper and flip off cap, together with a user label and sanitising swab. The product contains no antimicrobial preservative.

6.6 Special Precautions for Disposal

The disposal of all radioactive wastes should be carried out in accordance with the NHMRC 'Code of Practice for the Disposal of Radioactive Wastes by the User, (1985)'.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Summary Table of Changes