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STABILISED CERETEC 500 MICROGRAMS KIT FOR RADIOPHARMACEUTICAL PREPARATION

Active substance(s): EXAMETAZIME

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1177371 GBR_1177371 GBR 15.11.12 13.59 Side 1

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
Bladder
Bone surfaces
Brain
Breast
Gall bladder
GI tract
Stomach
SI
ULI
LLI

5.3E-03
2.3E-02
5.1E-03
6.8E-03
2.0E-03
1.8E-02

Heart
Kidneys
Liver
Lungs
Muscles
Oesophagus
Ovaries
Pancreas

3.7E-03
3.4E-02
8.6E-03
1.1E-02
2.8E-03
2.6E-03
6.6E-03
5.1E-03

Red marrow
Skin
Spleen
Testes
Thymus
Thyroid
Uterus

3.4E-03
1.6E-03
4.3E-03
2.4E-03
2.6E-03
2.6E-02
6.6E-03

Remaining organs

3.2E-03

Effective dose
(mSv/MBq)

9.3E-03

6.4E-03
1.2E-02
1.8E-02
1.5E-02

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.

Document: 1177371 GBR Version: 0

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 strawcoloured 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 99mTcexametazime 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-hydrolysedtechnetium-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

HEALTHCARE PROFESSIONAL
INFORMATION

Stabilised Ceretec™
500 micrograms kit for
radiopharmaceutical
preparation
Exametazime

1177371

1177371 GBR

1177371 GBR_1177371 GBR 15.11.12 13.59 Side 2

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.

Document: 1177371 GBR Version: 0

5

Pharmacological properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceutical for central
nervous system, technetium (99mTc) exametazine, ATC Code: V09AA01.

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.

6.3 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
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
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 12.

9

UK

Date of First authorisation/Renewal of the authorisation
Date of first authorisation

Date of last renewal

09 November 1999

29 November 2003

10 Date of Revision of the text
11/2012

1177370 GBR_1177370 GBR 15.11.12 13.56 Side 1

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.
6. Further information
What Stabilised Ceretec contains
• The active ingredient is exametazime. Each vial
of Stabilised Ceretec contains 500 micrograms
of exametazime.
• 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.

Document: 1177370 GBR Version: 0

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

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.

GE Healthcare

PATIENT
INFORMATION

Stabilised Ceretec TM
500 micrograms kit for
radiopharmaceutical
preparation
Exametazime

1177370

1177370 GBR

1177370 GBR_1177370 GBR 15.11.12 13.56 Side 2

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.
In this leaflet:
1. What Stabilised Ceretec is and what it is used
for
2. Before you are given Stabilised Ceretec
3. How Stabilised Ceretec is given
4. Possible side effects
5. How to store Stabilised Ceretec
6. 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.

Document: 1177370 GBR Version: 0

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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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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