PACKAGE LEAFLET: INFORMATION FOR THE USER
METASTRON 37 MBq/ml solution for injection
(called Metastron in this leaflet)
• Prostate cancer affects the ‘prostate gland’.
The gland is found only in men.
Strontium-89 chloride
The use of Metastron does involve exposure to
amounts of radioactivity. Your doctor and the
nuclear medicine doctor have considered that
the clinical benefit that you will obtain from
the procedure with the radiopharmaceutical
outweighs the risk due to radiation.
Read all of this leaflet carefully before you
are given this medicine because it contains
important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your
nuclear medicine doctor who will supervise the
procedure.
• If you get any side effects, talk to your nuclear
medicine doctor. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet:
1. What Metastron is and what it is used for
2. What you need to know before Metastron is
used
3. How Metastron is used
4. Possible side effects
5. How Metastron is stored
6. Contents of the pack and other information
1. What Metastron is and what it is used for
Metastron is a ‘radiopharmaceutical’ medicine for
therapy only.
• It contains an active ingredient called
‘strontium chloride’.
• It can be used to lower pain in your bones,
which may happen if you have prostate cancer.
Code Reads
L-R
Your doctor will tell you anything else you need to
know about how Metastron works
2. What you need to know before Metastron
is used
Metastron must not be used:
• If you are allergic (hypersensitive) to Metastron
or any of the other ingredients of this medicine
(listed in Section 6.)
• If you have a blood disorder such as low levels
of platelets and white blood cells
Warnings and precautions
Talk to your nuclear medicine doctor before you
are given Metastron if you:
• have kidney problems
• have been given Metastron before (within the
last 12 weeks)
• have a short life expectancy (less than 4 weeks)
Before administration of Metastron you should:
• drink plenty of water before the start of the
examination in order to urinate as often as
possible during the first hours after the study.
Children and adolescents
This medicine is not for use in children.
Other medicines and Metastron
Tell your nuclear medicine doctor or nurse if you
are taking, have recently taken or might take any
other medicines, including medicines obtained
without a prescription. This is because some
medicines can affect the way Metastron works.
Before your treatment tell your doctor or nurse if
you are taking any of the types of medicine below.
This is because they may affect the results of your
treatment.
• Medicines used for calcium therapy, such as
calcium carbonate.
If you are not sure if the above applies to you, talk
to your doctor or nurse before having Metastron.
Driving and using machines
Ask your doctor if you can drive or use machines
after you have been given Metastron.
Tests you may have with Metastron
You may have blood samples taken and your
blood monitored.
3. How Metastron is used
There are strict laws on the use, handling and
disposal of radiopharmaceutical products.
Metastron will only be used in special controlled
areas. This product will only be handled and given
to you by people who are trained and qualified to
use it safely. These persons will take special care
for the safe use of this product and will keep you
informed of their actions.
The nuclear medicine doctor supervising the
procedure will decide on the quantity of Metastron
to be used in your case. It will be the smallest
quantity necessary to get the desired effect.
The quantity to be administered usually
recommended for an adult is 150 MBq
(megabecquerel, the unit used to express
radioactivity).
Administration of Metastron and conduct of
the procedure
Metastron is given as a single injection into your
vein (intravenous injection).
Duration of the procedure
Your nuclear medicine doctor will inform you
about the usual duration of the procedure.
After administration of Metastron, you should:
• Urinate frequently in order to eliminate the
product from your body.
• Take the following actions for the first week
after you have been given Metastron because it
will be in your urine:
• If a ‘normal’ toilet is available you should
always use that instead of a urinal.
• You should flush the toilet twice after using it.
• You should wipe up any spilled urine with a
tissue and flush it away.
• You should always wash your hands after
using the toilet.
• Immediately wash your bedding or clothes
if they become soiled with urine. Wash them
separately from other clothes and rinse
thoroughly.
• If you use any urine collection device ask
your doctor or nurse about any changes on
how to use it.
• Clean up blood if you cut yourself after being
given Metastron. You should wash away any
spilled blood for the first week after being given
Metastron because it will be in your blood.
turn over ➤
The nuclear medicine doctor will inform you if
you need to take any special precautions after
receiving this medicine. Contact your nuclear
medicine doctor if you have any questions.
If you have been given more Metastron than you
should
An overdose is unlikely because you will only receive
a single dose of Metastron precisely controlled
by the nuclear medicine doctor supervising the
procedure. However, in the case of overdose, you
will receive the appropriate treatment.
Should you have any further questions on the use
of Metastron, please ask the nuclear medicine
doctor who supervises the procedure.
4. Possible side effects
Like all medicines, Metastron can cause side
effects, although not everybody gets them.
The following side effects may happen with this
medicine:
Very common (≥1/10),
• increase in pain within the first few days after
the injection
• tests may show blood (haematological) toxicity.
This can include a decrease in platelets and
white blood cells. Signs of this would be
bleeding or bruising more easily than usual.
• decrease in haemoglobin and red blood cells
Common (≥1/100 to <1/10),
• sudden sensation of feeling hot, usually in the
face and neck
Reporting of side effects
If you get any side effects, or if you notice any side
effects not listed in this leaflet, please tell your
nuclear medicine doctor.
You can also report side effects directly to:
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra
By reporting side effects, you can help provide
more information on the safety of this medicine.
5. How Metastron is stored
You will not have to store this medicine. This
medicine is stored under the responsibility of the
specialist in appropriate premises. Storage of
radiopharmaceuticals will be in accordance with
national regulations on radioactive materials.
The following information is intended for the
specialist only.
Metastron is kept out of the sight and reach of
children.
Metastron must not be used after the expiry date
and time, which are stated on the label after ‘EXP’.
Store below 25oC. Do not refrigerate or freeze.
6. Contents of the pack and other information
What Metastron contains
• The active ingredient is strontium-89 chloride.
Each ml of Metastron contains 37 MBq/ml
(Megabecquerel – the unit in which radioactivity
is measured) of strontium-89 chloride at a fixed
time.
• The other ingredients are strontium chloride
and water for injections.
What Metastron looks like and contents of the
pack
GE Healthcare
Metastron is supplied as a single colourless glass
vial containing a clear, colourless solution for
injection.
INFORMATION FOR THE USER
Marketing Authorisation Holder
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
37 MBq/ml solution
for injection
Strontium-89 chloride
SMS2PIE
Manufacturer
GE Healthcare Limited
The Grove Centre
White Lion Road
Amersham
Buckinghamshire HP7 9LL
United Kingdom
9 9 9 9 9 9 9
P/6261/03
This leaflet was last revised in November 2016.
Marketing Authorisations
Ireland: PA 0240/006/001
Metastron is a trademark of GE Healthcare.
GE and the GE Monogram are trademarks of
General Electric Company.
Code Reads
R-L
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Metastron 37 MBq/ml Solution for Injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Strontium-89 chloride: 37 MBq/ml
A solution of the active ingredient strontium-89 chloride (150 MBq) in
4ml water.
Strontium-89 is a pure beta emitter with an energy of 1.492 MeV and a halflife of 50.5 days.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection.
Clear, colourless solution.
4
CLINICAL PARTICULARS
4.1 Therapeutic indications
Metastron is indicated as an adjunct to and as an alternative to external
beam radiotherapy for the palliation of pain from bone metastases
secondary to prostatic carcinoma at the stage of hormone therapy failure.
4.2 Posology and method of administration
Posology
Adults
Metastron is an aqueous solution for intravenous injection and should
be used without dilution. The recommended dose is 150 MBq (4 mCi) per
injection, based on the average patient weight of 70 kg.
Alternatively, in particularly heavy or light framed patients a dose of 2 MBq
(55 µCi)/kg ‘fat-free’ body weight may be used. This dosage is suitable
for the elderly. Repeat administrations should not be performed within
3 months of the previous Metastron injection. Further administrations
are not indicated in patients who have not responded to a previous
administration of Metastron.
Calcium-like flushing sensation can occur with rapid administration of the
product. Flushing sensation should not occur if the compound is infused
slowly.
Elderly Population
No dose adjustment is recommended based on age.
Renal impairment
Careful consideration of the activity to be administered is required since an
increased radiation exposure is possible in these patients.
Paediatric population
The product is not for administration to children.
Method of administration
Metastron is for single use only. (For repeat use after several weeks see
section 4.4).
The instructions for preparation of radiopharmaceuticals are given in
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.
Metastron should not be used as a primary treatment for cord compression
secondary to spinal metastases where more rapid treatment may be
necessary.
Use of the product in patients with evidence of seriously compromised
bone marrow, particularly low neutrophil and platelet counts, is not
recommended unless the potential benefit of the treatment is considered
to outweigh the risk.
4.4 Special warnings and precautions for use
Bone marrow depression may increase due to administration of Metastron.
Administer with caution to patients suspected of bone marrow depression
as evidenced by low platelet counts and white blood cell counts or a gradual
decrease in these blood cell counts prior to administration. The use of
Metastron is contraindicated in patients with seriously compromised bone
marrow function (see section 4.3).
Individual benefit/risk justification:
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 therapeutic result.
Renal impairment:
Careful consideration of the benefit risk ratio in patients with renal
impairment is required since an increased radiation exposure is possible.
Paediatric population:
For information on the use in 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. Special precautions, such
as urinary catheterisation, should be taken following administration of
Metastron to patients who are significantly incontinent to minimise risks
of radioactive contamination.
International guidelines for disposal of
radioactive waste must be followed.
Specific warnings:
Use of the product in patients with evidence of seriously compromised
bone marrow, particularly low neutrophil and platelet counts, is not
recommended unless the potential benefit of the treatment is considered
to outweigh the risk. The following values can be considered in general:
Leukocytes >3000/µl, platelets >100,000/µl and haemoglobin (Hb) >90 g/l.
It is recommended that the haematology of patients should be monitored. In
considering repeat administration of Metastron the patient’s haematological
response to his initial dose, current platelet levels and any other evidence of
marrow depletion should all be carefully considered.
A cytotoxic agent may be administered to a patient who has previously
received Metastron provided that haematological parameters are stable
and within the normal range. An interval of 12 weeks is recommended
between administrations of the two therapies.
Therapy with Metastron is inappropriate for patients with a life expectancy
less than 4 weeks. Considering the latency in the onset of the palliative
effect, is more beneficial in patients with a relatively long life expectancy.
It should be taken into account in patient management that the expected
time of onset of pain relief is 10 to 20 days following Metastron administration.
It is not recommended that Metastron is administered to patients with very
short life expectancies. Retention of 89Sr in metastatic bone lesions is
probably 90 days or more and thus significantly prolonged compared with
retention in normal bone tissue.
Care should be exercised in the pre-treatment assessment of the
haematological status of patients who, for the same cause, have previously
received extensive bone radiation and/or another injectable bone-seeking
isotope.
It is important that information concerning this treatment and the associated
safety precautions are given to the patient, relatives and hospital staff. Users
should refer to the accompanying Patient Information.
A calcium-like flushing sensation has been observed in patients following
a rapid (less than 30 second injection) administration. See section 4.2.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose,
i.e. essentially sodium-free.
For precautions with respect to environmental hazard see section 6.6.
4.5 Interaction with other medicinal products and other forms of
interaction
Calcium therapy should be discontinued at least two weeks before Metastron
administration.
4.6 Fertility, pregnancy and lactation
Not relevant due to indication.
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)
System Organ Class
Blood and lymphatic
system disorders
Frequency
Very common
Vascular disorders
General disorders and
administration site
conditions
Common
Very common
Adverse reaction
Bone marrow depression,
including serious
thrombocytopenia, serious
leukopenia, reduced
haemoglobin or low red blood
cell count (see section 4.4).
Flushing
Pain exacerbated (transient)
Adverse effects may include an exacerbation of pain within the first
few days of administration. In clinical trials this effect was temporary
and controlled with analgesics. Some degree of haematological toxicity,
including thrombocytopenia and leucopenia, is to be expected following
administration of Metastron. Typically, platelets will be depressed by about
30% (95% confidence limits 10-55%) compared to pre-administration levels.
Because of the natural progress of their disease, more severe depression of
platelet levels may be observed in some patients.
Exposure to ionising radiation is linked with cancer induction and a potential
for development of hereditary defects.
The radiation dose resulting from therapeutic exposure may result in higher
incidence of cancer and mutations.
In all cases it is necessary to ensure that the risks of the radiation are less
than from the disease itself. The effective dose is 465 mSv when the maximal
recommended activity of 150 MBq is administered.
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: HPRA Pharmacovigilance,
Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.
Website: www.hpra.ie; E-mail: [email protected].
4.9 Overdose
Not applicable.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: therapeutic radiopharmaceuticals, pain
palliation (bone seeking agents) strontium (89Sr) chloride
ATC code: V10BX01
The chemical properties of strontium enable it to imitate calcium in vivo,
rapidly localising in proliferating bone. Strontium-89 is a beta emitter
(100%), with a physical half-life of 50.5 days. The range of ß-particles
in tissue is 0.8 cm.
5.2 Pharmacokinetic properties
Distribution
The extent of uptake and retention of strontium-89 will depend on the
metastatic involvement of the skeleton.
Organ uptake
The longer retention of strontium-89 in metastatic lesions enables the
isotope to deliver a larger radiation dose to metastases whilst delivering
a relatively small dose to bone marrow.
Elimination
Strontium which is not localised in the skeleton is excreted mainly via the
urine with a small amount via the faeces.
Half-life
Strontium is retained in lesions with a long biological half-life compared to
the physical half-life of strontium-89, whilst strontium taken up into normal
bone exhibits a half-life of about 14 days.
Renal/hepatic impairment
The pharmacokinetics in patients with renal or hepatic impairment has not
been characterised.
5.3 Preclinical safety data
The chemical toxicity of non-radioactive strontium chloride is well
documented and of little consequence, particularly in terms of the
risk/benefit to the patient for whom this product is intended.
8 MARKETING AUTHORISATION NUMBERS
PA 0240/006/001
6
Date of first authorisation:
Date of last renewal:
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Strontium chloride
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be
mixed with other medicinal products.
6.3 Shelf life
The shelf life of the product is 28 days post the radioactivity reference date.
6.4 Special precautions for storage
Store below 25°C. Do not refrigerate or freeze.
Storage of radiopharmaceuticals should be in accordance with national
regulations on radioactive materials.
6.5 Nature and contents of container
The product is supplied in a neutral glass vial as an aqueous solution.
The vial is sealed with a PTFE coated rubber closure and metal overseal
and is individually packed. Each vial is packed within a radiation shielding
container of lead metal.
Pack size: A single 150 MBq vial.
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. Their 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.
If at any time in the preparation of this product the integrity of the container
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 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.
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20 August 1991
20 August 2006
10 DATE OF REVISION OF THE TEXT
November 2016
11 DOSIMETRY
The estimated radiation doses that would be received by normal healthy
adults from the intravenous administration of 1 MBq of strontium-89 are
given in the table below. Data are taken from Publication 53 of the ICRP
(International Commission on Radiological Protection, Radiation Dose to
Patients from Radiopharmaceuticals, Pergamon Press 1987).
Radiation doses to normal adults from the intravenous injection of
strontium-89
Organ
Absorbed radiation dose (mGy/MBq)
Bone surfaces
17.0
Red bone marrow
11.0
Lower large intestine wall
4.7
Bladder wall
1.3
Testes
0.78
When osseous metastases are present significantly enhanced localisation of
the radiopharmaceutical will occur with correspondingly higher doses to the
metastases relative to other organs.
The absorbed dose to vertebral metastases has been measured in a group
of 10 patients with widely varying extends of disease*. The minimum,
maximum and mean doses in this group are listed below.
Radiation dose to vertebral metastases from intravenous injection of
strontium-89
Absorbed radiation dose (mGy/MBq)
Minimum
60
Maximum
610
Mean
230
*Blake, G M et al Strontium-89 therapy: Measurement of absorbed dose to
skeletal metastases. J Nucl Med 1988; 29(4), 549-557.
The Effective Dose for strontium-89 is 465 mSv per 150 MBq (ICRP 80, 1998).
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
Metastron is an aqueous solution for intravenous injection and should be
used without dilution. See section 4.2.
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.
13 OTHER INFORMATION
Manufacturer
GE Healthcare Limited
The Grove Centre
White Lion Road
Amersham
Buckinghamshire HP7 9LL
United Kingdom
GE Healthcare
HEALTHCARE PROFESSIONAL
INFORMATION
Metastron is a trademark of GE Healthcare.
GE and the GE Monogram are trademarks of General Electric Company.
37 MBq/ml solution
for injection
Strontium-89 chloride
SMS2PIE
9999999
L/6208/04