Ceretec 500 Micrograms Kit For Radiopharmaceutical Preparation
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PACKAGE LEAFLET: INFORMATION FOR THE USER
Stabilised Ceretec 500 micrograms kit for radiopharmaceutical preparation
Exametazime
(called Stabilised Ceretec in this leaflet)
Read all of this leaflet carefully before you are given Stabilised Ceretec.
• 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.
this leaflet:
What Stabilised Ceretec is and what it is used for
Before you are given Stabilised Ceretec How Stabilised Ceretec is given Possible side effects How to store Stabilised Ceretec Further information
1. What Stabilised Ceretec is and what it is used for
This medicine is for diagnostic use only. It is used only to help identify illness.
Stabilised Ceretec is a 'radiopharmaceutical' medicine. It is given before a scan and helps a special camera see inside a part of your body.
• It contains an active ingredient called 'exametazime'. This is mixed with another ingredient called 'technetium' before it is used.
• 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 how much blood is flowing through your brain. This may be important to know after a stroke, if you have fits or epilepsy, Alzheimer's disease or a similar type of dementia. It may also be used in people who have migraine (headaches) or a brain tumour.
2. Before you are given Stabilised Ceretec
You should not be given Stabilised Ceretec:
• If you are allergic (hypersensitive) to the active ingredient or any other ingredient. (Listed in Section 6).
Do not have Stabilised Ceretec if the above applies to you. If you are not sure talk to your doctor or nurse.
Take special care with Stabilised Ceretec
Check with your doctor or nurse before having Stabilised Ceretec:
• If the person who will be given this medicine is a child.
• If you are pregnant or think you might be pregnant.
• If you are on a low sodium diet.
Taking other medicines
Please tell your doctor or nurse 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 Stabilised Ceretec works.
No medicines have been reported that affect the way Stabilised Ceretec works. But it is still best to tell your doctor or nurse if you are taking any other medicines.
Pregnancy and breast-feeding
You must tell your doctor if you are pregnant or think you may be pregnant. Your doctor will only use this product if it is considered that the benefit outweighs the risk.
Do not breast-feed if you are given Stabilised Ceretec. This is because small amounts of 'radioactivity' may pass into the mother's milk. If you are breast-feeding, your doctor may wait until you have finished breast-feeding before using Stabilised Ceretec. If it is not possible to wait your doctor will ask you to:
• stop breast-feeding for 12 hours or longer, 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 Stabilised Ceretec.
Important information about Stabilised Ceretec
When Stabilised Ceretec 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 Stabilised Ceretec is given
Stabilised Ceretec will be given to you by a specially trained and qualified person.
• Stabilised Ceretec 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 on the dose that is best for you.
The usual dose is:
• One single injection.
If you are given more Stabilised Ceretec than you should
Stabilised Ceretec 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, Stabilised Ceretec can cause side effects, although not everybody gets them.
Allergic reactions
If you have an allergic reaction when you are in hospital or a clinic having the scan, tell the doctor or nurse straight away. The signs may include:
• skin rash or itching or flushing
• swelling of the face
• difficulty in breathing.
If any of the side effects above happen after you leave the hospital or clinic, go straight to the casualty department of your nearest hospital.
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.
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5. How to store Stabilised Ceretec
Stabilised Ceretec 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.
This leaflet was last approved in 11/2012.
Marketing Authorisation
UK: PL 00221/0136
Ceretec is a trademark of GE Healthcare.
GE and the GE Monogram are trademarks of General Electric Company.
6. Further information
What Stabilised Ceretec contains
• The active ingredient is exarmetaziime. Each vial of Stabilised Ceretec contains 500 micrograms of exarmetaziime.
• The other ingredients are stannous chloride dihydrate, sodium chloride, cobalt (II) chloride 6-hydrate and water for injections.
What Stabilised Ceretec looks like and contents of the pack
Stabilised Ceretec is supplied as a kit for radiopharmaceutical preparation. The kit contains:
• two vials containing 500 micrograms exametazime and two vials of a solution for injection, or
• five vials containing 500 micrograms exametazime and five vials of a solution for injection.
Marketing Authorisation Holder
GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA United Kingdom
Manufacturer
GE Healthcare AS Nycoveien 1-2 0401 OSLO Norway
GE Healthcare
PATIENT
INFORMATION
Stabilised Ceretec™
500 micrograms kit for radiopharmaceutical preparation
Exametazime
1177370
1177370 GBR
PACKAGE LEAFLET: INFORMATION FOR HEALTHCARE PROFESSIONAL
1 Name of the medicinal product
Stabilised Ceretec 500 micrograms kit for radiopharmaceutical preparation
2 Qualitative and Quantitative Composition
Each vial contains exametazime 500 micrograms.
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.
Stabilised Ceretec is reconstituted with Sodium Pertechnetate (99mTc) Injection Ph.Eur. (not included in this kit) to prepare stabilised Technetium (99mTc) Exametazime Injection.
3 Pharmaceutical Form
Kit for radiopharmaceutical preparation for injection.
White powder.
4 Clinical Particulars
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
Technetium-99m 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.
4.2 Posology and method of administration
Dose for adults and the elderly:
350-500 MBq by direct intravenous injection.
Normally a once-only diagnostic procedure.
Technetium-99m exametazime is not recommended for administration to children.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
There are no known special warnings and precautions for use for this product.
4.5 Interaction with other medicinal products and other forms of interaction
No drug interactions have been reported to date.
4.6 Pregnancy and lactation
No data are available on the use of this product in human pregnancy. Animal reproduction studies have not been performed.
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. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation should be considered. Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only imperative investigations should be carried out during pregnancy, when the likely benefit exceeds the risk incurred by the mother and the foetus.
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. Breast feeding can be restarted when the level in the milk will not result in a radiation dose to the child greater than 1mSv.
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
A very few cases of mild hypersensitivity evidenced by the development of an urticarial erythematous rash have been reported following direct intravenous injection of the non-stabilised formulation of technetium-99m exametazime. No additional undesirable effects have been attributable to administration of the cobalt stabilised formulation.
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 low frequency because of the low radiation doses incurred.
For most diagnostic investigations using a nuclear medicine procedure the effective dose is less than 20 mSv. Higher doses may be justified in some clinical circumstances.
4.9 Overdose
In the event of the administration of a radiation overdose frequent micturition and defaecation should be encouraged in order to minimise the absorbed dose to patient.
At the chemical concentrations and activities used for diagnostic procedures technetium-99m exametazime does not appear to exert any pharmacodynamic effects.
5.2 Pharmacokinetic properties
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.
5.3 Preclinical safety data
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.
6 Pharmaceutical particulars 6.1 List of excipients
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
6.3 Shelf life
26 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.
6.4 Special precautions for storage
Store below 25°C. Do not freeze.
Storage should be in accordance with national regulations for radioactive materials.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature and contents of container
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.
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.
7 Marketing Authorisation Holder
GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA United Kingdom
8 Marketing Authorisation Number
UK: PL 00221/0136
9 Date of First authorisation/Renewal of the authorisation
|
Date of first authorisation |
Date of last renewal | |
|
UK |
09 November 1999 |
29 November 2003 |
10 Date of Revision of the text
11/2012
5 Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceutical for central nervous system, technetium (99mTc) exametazine, ATC Code: V09AA01.
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.
Document: 1177371 GBR Version: 0
Document: 1177371 GBR Version: 0
11 DOSIMETRY
The table below shows the dosimetry as calculated according to the Publication ICRP 62 (International Commission on Radiological Protection, Radiological Protection in Biomedical Research, Pergamon Press 1991).
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) Adult |
|
Adrenals |
5.3E-03 |
|
Bladder |
2.3E-02 |
|
Bone surfaces |
5.1E-03 |
|
Brain |
6.8E-03 |
|
Breast |
2.0E-03 |
|
Gall bladder |
1.8E-02 |
|
GI tract | |
|
Stomach |
6.4E-03 |
|
SI |
1.2E-02 |
|
ULI |
1.8E-02 |
|
LLI |
1.5E-02 |
|
Heart |
3.7E-03 |
|
Kidneys |
3.4E-02 |
|
Liver |
8.6E-03 |
|
Lungs |
1.1E-02 |
|
Muscles |
2.8E-03 |
|
Oesophagus |
2.6E-03 |
|
Ovaries |
6.6E-03 |
|
Pancreas |
5.1E-03 |
|
Red marrow |
3.4E-03 |
|
Skin |
1.6E-03 |
|
Spleen |
4.3E-03 |
|
Testes |
2.4E-03 |
|
Thymus |
2.6E-03 |
|
Thyroid |
2.6E-02 |
|
Uterus |
6.6E-03 |
|
Remaining organs |
3.2E-03 |
|
Effective dose | |
|
(mSv/MBq) |
9.3E-03 |
Effective Dose is 4.7 mSv/500 MBq (70 kg individual).
The biodistribution and hence the radiation dosimetry of technetium-99m exametazime is not significantly altered by in vitro cobalt stabilisation.
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
The radiopharmaceutical may 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 licences of the local competent official organisations (see section 6.6).
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.
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.
Procedure for preparation of cobalt stabilised technetium-99m
exametazime for intravenous injection:
Use aseptic technique throughout.
(1) Place the exametazime vial in a shielding container and swab the closure with the sanitising swab provided.
(2) Using a 10 ml syringe, inject into the shielded vial 5 ml of sterile eluate from a technetium-99m generator (see notes 1 - 6). Before withdrawing the syringe from the vial withdraw 5 ml of gas from the space above the solution to normalise the pressure in the vial. Shake the shielded vial for 10 seconds to ensure complete dissolution of the powder.
(3) Between 1 and 5 minutes after reconstitution, inject 2 ml of cobalt stabiliser solution into the shielded vial using a 3 ml syringe. Before withdrawing the syringe from the vial, withdraw 2 ml of gas from the space above the solution to normalise the pressure in the vial. Shake the shielded vial for 10 seconds to ensure complete mixing.
(4) Assay the total radioactivity and calculate the volume to be injected.
(5) Complete the label provided and attach to the vial.
(6) Use the stabilised product between 30 minutes and 5 hours after preparation. Individual patient doses may be stored aseptically in a capped syringe if required (see note 7).
(7) Discard any unused material.
Note:
(1) For the highest radiochemical purity reconstitute with freshly eluted technetium-99m generator eluate.
(2) The technetium-99m generator eluate must be used within 4 hours of elution from a generator that has already been eluted within the previous 24 hours.
(3) 0.37 - 1.11 GBq technetium-99m may be added to the vial.
(4) Before reconstitution the generator eluate may be adjusted to the correct radioactive concentration (0.37 - 1.11 GBq in 5 ml) by dilution with sodium chloride for injection.
(5) [99mTc]pertechnetate complying with the specifications prescribed by the USP and BP/Ph.Eur. Monographs on Sodium Pertechnetate (99mTc) Injection should be used.
(6) The cobalt stabilised technetium-99m exametazime is a pale straw-coloured solution and the pH is in the range 5.0 - 8.0.
(7) When Stabilised Ceretec preparations are transferred to individual patient syringes, a small volume of the headspace gas must be withdrawn from the vial into the syringe after solution transfer to ensure that no solution remains in contact with the syringe needle prior to administration to the patient.
(8) The shelf life of the reconstituted Ceretec component without the addition of the cobalt stabiliser is only 30 minutes.
Radiochemical purity measurement
Three potential radiochemical impurities may be present in prepared Technetium (99mTc) Exametazime Injection. These are a secondary 99mTc-exametazime complex, free [99mTc]pertechnetate and reduced-hydrolysed-
technetium-99m. A combination of two chromatographic systems is necessary for the determination of the radiochemical purity of the injection. Test samples are applied by needle approximately 2.5 cm from the bottom of two Varian SA strips (2 cm (±2 mm)x 20 cm). The strips are then immediately placed in prepared ascending chromatography development tanks, one containing butan-2-one and the other 0.9% sodium chloride (1 cm depth fresh solvent). After a 14 cm elution the strips are removed, solvent fronts marked, the strips dried and the distribution of activity determined using suitable equipment.
Interpretation of chromatograms
System 1 (Varian SA:butan-2-one(methyl ethyl ketone))
Secondary 99mTc-exametazime complex and reduced-hydrolysed-technetium-99m remain at the origin.
Lipophilic 99mTc-exametazime complex and [99mTc]pertechnetate migrate at Rf 0.8-1.0.
System 2 (Varian SA:0.9% sodium chloride)
Lipophilic 99mTc-exametazime complex, secondary 99mTc-exametazime complex and reduced-hydrolysed-technetium-99m remain at the origin. [99mTc]pertechnetate migrates at Rf 0.8-1.0.
I. Calculate the percentage of activity due to both secondary 99mTc exametazime complex and reduced-hydrolysed-technetium-99m from System 1 (A%). Calculate the percentage of activity due to [99mTc]pertechnetate from System 2 (B%).
II. The radiochemical purity (as percentage lipophilic technetium-99m exametazime complex) is given by:
100-(A%+B%) where:
A% represents the level of secondary technetium-99m exametazime complex plus reduced-hydrolysed technetium-99m.
B% represents the level of [99mTc]pertechnetate.
A radiochemical purity of at least 80% may be expected provided the test samples have been taken and analysed within 5 hours of the preparation of the stabilised product.
13 OTHER INFORMATION
Manufacturer
GE Healthcare AS Nycoveien 1-2
0401 Oslo Norway
Ceretec is a trademark of GE Healthcare.
GE and the GE Monogram are trademarks of General Electric Company.
GE Healthcare
1177371
1177371 GBR
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