January 31st, 2011
SUMMARY OF PRODUCT CHARACTERISTICS
for
Sodium Chromate (51Cr) Solution, GE Healthcare, radiopharmaceutical precursor
1.
NAME OF THE MEDICINAL PRODUCT
Sodium Chromate [51Cr] Solution, GE Healthcare
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Sodium [51Cr] chromate:
37-185MBq/vial
at the activity reference date
The formulation contains 3.1 to 31µg/ml sodium chromate.
Chromium-51 has a physical half-life of approximately 28 days and decays by electron
capture emitting gamma radiation with an energy of 0.32 MeV.
This medicinal product contains: sodium 3.55 mg/ml.
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Radiopharmaceutical precursor.
Solution for injection
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
This medicinal product is for diagnostic use only.
Sodium chromate [51Cr] is used for in vitro/ex vivo red blood cell labelling and is intended
only for diagnostic use.
The radio labelling of erythrocytes facilitates the determination of red cell volume, for
example, in the diagnosis of polycythaemias, anaemias associated with splenomegaly, and
“pseudoanaemia” secondary to an expanded plasma volume. Similarly red cell survival
studies can be performed in patients with haemoglobinopathies, haemolytic anaemias and
in whom there is a need to assess transfusion requirements after blood incompatibility
reactions. Cr-51 cell tagging may also be used to establish sites of cell sequestration
116100029
Page 1 of 7
(liver, spleen) particularly when considering splenectomy in patients with chromic
haemolysis or idiopathic thrombocytopenic purpura.
Cr-51 tagged erythrocytes may be used to quantify chronic gastrointestinal blood loss.
4.2
Posology and method of administration
Sodium Chromate (51Cr) Solution is intended only for in vitro labelling of red blood cells
which are subsequently re-injected into the patient.
For red cell volume and survival, 10-15 ml of blood is removed by venesection and
centrifuged and the red cells incubated with the radioactive solution. To minimise damage
to red cells blood pH should be maintained using appropriate additives. Excess unbound
isotope may be removed by washing the cells in isotonic saline or plasma. The cells are
then re-suspended in saline before re-injection.
Serial blood samples may then be subsequently removed for counting and radiokinetic
calculations. Sequestration sites in the body are identified by external counting. In chronic
gastrointestinal bleeding the activity in venous blood is compared to that in the faeces.
The following activities for red cell labelling are those recommended by the International
Committee for Standardisation in Haematology for administration to patients.
Estimation of red cell volume (RCV):
Estimation of red cell survival (RCS):
individual
Red cell survival and sequestration:
Detection of gastrointestinal bleed:
3.7 - 7.4 kBq/kg body weight
i.e.:
260 - 520 kBq/70 kg individual
 18.5 kBq/kg body weight
i.e.:
740 - 1300 kBq/70 kg
 50 kBq/kg body weight
i.e.:
 4 MBq/70 kg body weight
0.74 - 4 MBq/70 kg individual
Paediatric administration:
Detailed biodistribution data in children are not available. However, in keeping with
normal practice, the activities administered to children should be derived fractions of those
advised in adults. These are calculated according to body weight or surface area. The
activities proposed below are based upon averaged data and offered only as guidance.
Advised paediatric regimens expressed as a proportion of recommended adult
activities
Factor
Newborn 1 year
5 year
10 year
15 year
18 year
based on
body:
weight
x 0.06
x 0.30
x 0.30
x 0.51
x 0.94
x 1.0
surface
x 0.14
x 0.33
x 0.43
x 0.59
x 0.91
x 1.0
area
General correction factors have been advised as below
3 kg
10 kg
20 kg
30 kg
40-50 kg
68 kg
Approx.
Newborn 1 year
5 years
10 years
15 years
17 years+
age
adult dose x 0.1
x 0.27
x 0.46
x 0.62
x 0.76 x 0.99
0.88
116100029
Page 2 of 7
The instructions for preparation of radiopharmaceuticals are given in section 12.
4.3
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4
Special warnings and precautions for use
This product is not to be administered directly to the patient. The contents of the vial are
intended only for the in vitro labelling of red blood cells for subsequent intravenous
administration.
Excipients
This medicinal product contains sodium (3.55 mg/ml) less than 1 mmol/ml. i. e. essentially
sodium free.
4.5
Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed and no interactions have been reported to date.
4.6
Pregnancy and lactation
Pregnancy: Only imperative investigations should be carried out during pregnancy, when
the likely benefit exceeds the risk incurred by mother and foetus.
Radionuclide procedures carried out on pregnant woman also involve radiation doses to the
foetus. The expected absorbed dose to the uterus after administering an activity of 4 MBq
sodium (51Cr) chromate has been estimated to be 0.4 mGy although lower activities would
normally be utilised.
In particular, activities delivering doses of 0.5 mGy to the uterus are considered
hazardous.
Teratogenic effects are also reported to have been described after repeated administration
of chromium (III) salts in animal studies. Chromium-51 has a physical half-life of 28 days.
As chromate it is rapidly excreted in the urine but when bound to cells has an effective
half-life similar to its physical half-life. Nevertheless, in view of the likely maximal
chemical concentrations and radioactivities administered in the context of the described
haematological investigations, and the tight intracellular binding of the label in vivo, advice
on the avoidance of pregnancy need only extend until commencement of the next complete
menstrual cycle.
Women of childbearing potential: 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.
Lactation: Where such investigation is considered mandatory the monitoring of breast milk
radioactivity may be indicated. The suckling infant should not receive ingested activities
which would lead to overall exposures in excess of 1 mSv effective dose. 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 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.
116100029
Page 3 of 7
There are no data relating to the excretion of the chromium-51 after cell labelling in breast
milk.
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
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 reasonable achievable bearing in mind the need to obtain the intended diagnostic or
therapeutic 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. However, with this particular diagnostic agent only very low radiation
doses are to be anticipated (ED<1 mSv).
No adverse effects have been described after the administration of chromium labelled
blood cells despite clinical use over several decades.
4.9
Overdose
This agent is intended for use by competent personnel within an appropriate clinical
setting. As such the possibility of overdose is highly unlikely. However, in the event of
inadvertent administration of a significant excess of radioactivity, for example during red
cell labelling, haematological monitoring over several months could be necessary. It is not
possible to promote the excretion of the cell-bound chromate-51. No cases of overdose
have been reported to date.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other cardiovascular system diagnostic radiopharmaceuticals.
ATC: V09G X03
Chromium is a potentially toxic substance. At higher doses, it inhibits glycolysis (>10
g/ml and glutathione reductase (>5µg/ml). At the dose used in cell labelling (<2 g/ml of
packed red cells) sodium chromate [51Cr] solution has no effect on the cell to which it is
bound nor does it appear to exert other significant pharmacodynamic effects in man.
5.2
116100029
Pharmacokinetic properties
The hexavalent form of sodium [51Cr] chromate is normally used to radiolabel
erythrocytes. Reduction to the trivalent form can be effected by washing with agents such
as ascorbic acid thus enabling tight binding to the beta-chain of haemoglobin.Chromate-51
is thus released only on the death of the red cell. Other types of binding are less stable and
about 1% of the radio label may elute from the cells daily after injection into the
Page 4 of 7
bloodstream. Cumulative loss by elution may be as high as 40% over the lifespan of the
erythrocytes.
The chromium released is eliminated predominantly by the kidneys (96%) and is not taken
up by other cells. Any radiolabel carried into the gastrointestinal tract, due to intraluminal
bleeding, is not re-absorbed into the systemic circulation.
5.3
Preclinical safety data
Although the toxic effects of high chemical doses of chromium compounds are described,
the relatively small amounts utilised in cell labelling (not more than 10.8 µg chromate at 4
MBq) and also the tight binding of Chromate-51 to haemoglobin makes for low systemic
exposure during all envisaged diagnostic procedures.
6.
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Sodium chloride
Sodium chromate
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
75 day from the date of release.
The activity reference date is 60 days before expiry.
Once opened store in refrigerator (2ºC-8ºC) and use within 8 hours.
Since the product does not contain an antimicrobial preservative and is marketed for
multidose use, all doses from a single vial should be taken within a single working day and
the product stored at (2ºC-8ºC) after removal of the first aliquot.
6.4
Special precautions for storage
Store below 25o C. Do not freeze.
Store in original container and under appropriate shielding at room temperature.
Storage procedures should be in accordance with national regulations for radioactive
substances.
6.5
Nature and contents of container
10ml type I Ph.Eur., clear,colourless, borosilicate glass vial sealed with a PTFE-faced
butyl rubber closure and oversealed with an aluminium overseal with central aperture.
Each vial is packed within a radiation shielding container of lead metal and placed within a
sealed metal tin.
Pack sizes: 37MBq, 74 MBq, 185 MBq.
116100029
Page 5 of 7
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.
Any unused product or waste material should be disposed of in accordance with local
requirements for radioactive material.
7.
MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
Representative
GE Healthcare A/S
Park Allé 295
2605 Brøndby
8.
MARKETING AUTHORISATION NUMBER
DK R 1143
9.
DATE OF FIRST AUTHORISATION
31. januar 1995
10.
DATE OF REVISION OF THE TEXT
January 31st, 2011
11.
DOSIMETRY
The table below shows the shows the dosimetry as calculated according to the Publication 53
of the ICRP (International Commission of Radiological Protection, Radiation Dose to Patients
from Radiopharmaceuticals, Pergamon Press, 1987).
For this product the effective dose equivalent resulting from an administered activity of 4
MBq is typically 1 mSv (per 70 kg individual) (ICRP 80, 1998).
116100029
Page 6 of 7
Dosimetry of [51Cr] -labelled erythrocytes
Absorbed dose
per unit activity administered (mGy/MBq)
Organ
Adult
2.2E-01
7.5E-02
1.1E-01
9.9E-02
15 year
2.7E-01
9.7E-02
2.5E-01
1.0E-01
10 year
4.2E-01
1.4E-01
4.0E-01
1.7E-01
5 year
6.5E-01
2.2E-01
6.2E-01
2.6E-01
1 year
1.2E+00
3.7E-01
1.3E+00
4.6E-01
1.4E-01
9.5E-02
9.4E-02
8.1E-02
5.1E-01
1.6E-01
1.2E-01
1.2E-01
1.0E-01
6.1E-01
2.4E-01
1.8E-01
1.7E-01
1.6E-01
9.1E-01
3.5E-01
2.8E-01
2.8E-01
2.3E-01
1.4E+00
6.0E-01
5.0E-01
4.9E-01
4.2E-01
2.4E+00
Kidneys
Liver
Lungs
Ovaries
Pancreas
2.2E-01
2.4E-01
3.2E-01
8.2E-02
1.9E-01
2.6E-01
2.9E-01
4.1E-01
1.1E-01
2.2E-01
4.1E-01
4.6E-01
6.5E-01
1.6E-01
3.4E-01
6.4E-01
6.9E-01
1.0E+00
2.5E-01
5.0E-01
1.2E+00
1.3E+00
2.0E+00
4.5E-01
8.5E-01
Red marrow
Spleen
Testes
Thyroid
Uterus
1.4E-01
1.6E+00
6.3E-02
1.2E-01
8.5E-02
1.7E-01
2.1E+00
7.7E-02
1.6E-01
1.1E-01
2.6E-01
3.3E+00
1.1E-01
2.6E-01
1.6E-01
4.1E-01
5.1E+00
1.7E-01
4.2E-01
2.5E-01
7.6E-01
9.3E+00
3.3E-01
7.9E-01
4.5E-01
Other tissue
8.5E-02
Effective
dose equivalent
(mSv/MBq)
2.6E-01
Adrenals
Bladder wall
Bone surfaces
Breast
GI tract
Stomach wall
Small intestine
ULI wall
LLI wall
Heart
12.
1.0E-01
3.3E-01
1.5E-01
5.2E-01
2.3E-01
8.0E-01
4.2E-01
1.5E+00
INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
This 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.
116100029
Page 7 of 7