Kit For The Preparation Of Technetium [99m Tc] Colloidal Tin
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Hepatate
Kit for the preparation of Technetium [99mTc] Colloidal Tin Injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Stannous fluoride 125 micrograms /vial
Amerscan Hepatate II Agent is reconstituted with Sodium Pertechnetate (99mTc) Injection (not included in this kit) to prepare Technetium (99mTc) Colloidal Tin Injection.
Technetium-99m disintegrates with the emission of gamma radiation with an energy of 140 keV and a half life of 6 hours to technetium-99m which can be regarded as quasi stable.
The product before reconstitution contains:
• Sodium: 0.55 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.
3 PHARMACEUTICAL FORM
Kit for radiopharmaceutical preparation, powder for solution for injection.
A white or off-white powder.
4 CLINICAL PARTICULARS
Therapeutic indications
4.1
This medicinal product is for diagnostic use only. Reticuloendothelial imaging of liver and spleen
4.2 Posology and method of administration
The solution is administered intravenously.
In adults, the dose is 37 to 185 MBq for static imaging, other doses may be justifiable.
Imaging may commence 10 minutes after injection.
For dynamic imaging the dose in adults is 80 to 185 MBq, other doses may be justifiable.
Imaging may commence immediately after intravenous administration.
The dose to be administered in a child should be a fraction of the adult dose calculated from the body weight according to the following table:
Table: Dose calculation for use of Technetium (99mTc) Colloidal Tin Injection in children.
|
Fraction of adults dose: | ||
|
3 kg = |
22 kg = |
42 kg |
|
0.10 |
0.50 |
= 0.78 |
|
4 kg = |
24 kg = |
44 kg |
|
0.14 |
0.53 |
= 0.80 |
|
6 kg = |
26 kg = |
46 kg |
|
0.19 |
0.56 |
= 0.82 |
|
8 kg = |
28 kg = |
48 kg |
|
0.23 |
0.58 |
= 0.85 |
|
10 kg = |
30 kg = |
50 kg |
|
0.27 |
0.62 |
= 0.88 |
|
12 kg = |
32 kg = |
52-54 kg |
|
0.32 |
0.65 |
= 0.90 |
|
14 kg = |
34 kg = |
56-58 kg |
|
0.36 |
0.68 |
= 0.92 |
|
16 kg = |
36 kg = |
60-62 kg |
|
0.40 |
0.71 |
= 0.96 |
|
18 kg = |
38 kg = |
64-66 kg |
|
0.44 |
0.73 |
= 0.98 |
|
20 kg = |
40 kg = |
68 kg |
|
0.46 |
0.76 |
= 0.99 |
(Paediatric Task Group, European Association of Nuclear Medicine)
In very young children (up to 1 year) a minimum dose of 15 MBq is necessary to obtain images of sufficient quality.
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 specific warnings or precautions for use for this radiopharmaceutical product.
Interaction with other medicinal products and other forms of interaction
4.5
Drugs known to be associated with short-term or long-term hepatotoxicity, such as cancer chemotherapy, contraceptives, tetracyclines and drugs which may affect hepatic blood flow, such as certain anaesthetics, may be expected to affect the biodistribution patterns of radiolabelled colloids.
4.6 Pregnancy and lactation
When it is necessary to administer radioactive medicinal products to a woman 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 the 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 mother and 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 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 the breast feeding should be interrupted for 12 hours and the expressed feeds discarded. Breast feeding can be restarted when the level in milk will not result in a radiation dose to the child greater than 1 mSv.
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
Adverse reactions have occasionally been reported following the intravenous injection of colloids for liver and spleen imaging. The reactions generally involve vasomotor problems with malaise, bradycardia and lowered blood pressure. Angio-oedema, often facial, may occur, as may central chest or back pain with shortness of breath, occasionally complicated by true bronchospasm. Cutaneous reactions are relatively rare. The majority of reactions have been relatively mild but supportive treatment and/or an antihistamine may be required.
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
No specific therapy is possible in the event of the administration of an overdose.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, hepatic and reticulo endothelial system, technetium (99mTc) tin colloidal, ATC code:
V09DB04
At doses used for diagnostic procedures, technetium-99m colloidal tin does not appear to exert any pharmacodynamic effects
5.2 Pharmacokinetic properties
The process of ingestion of foreign materials including particulate matter by the cells of the reticuloendothelial system is well documented.
The site of phagocytosis depends on a number of factors including the size of the particles - large particles are trapped in the lungs, smaller particles are taken up in the liver and spleen.
Upon intravenous injection, technetium-99m colloidal tin is rapidly cleared from the blood by the reticuloendothelial system with a nominal clearance half-life of approximately one and a half minutes.
Uptake of the radioactive colloid by the components of the reticuloendothelial system is dependent upon relative blood flow rates and the functional capacity of phagocytic cells. In an average patient, 80 to 90% of the injected colloid particles are phagocytosed by the Kupffer cells of the liver, 5 to 10% are taken up by the spleen and by the bone marrow.
If hepatic function is impaired, particles will be phagocytosed in the lung and bone marrow more than in the liver. Increased uptake in the spleen indicates diffuse liver disease.
5.3 Preclinical safety data
A single dose toxicity study of the intravenous administration of a stannous fluoride based agent in rats showed no adverse reactions, changes in body weight or mortalities at a dose equivalent to at least 400 times the maximum human dose.
In rabbits a similar study showed no significant toxicity at 168 times the maximum human dose on a mg/kg basis.
Fourteen day subacute (IV) studies in mice and dogs produced no significant signs of toxicity at levels of 3108 and 490 times the maximum human dose.
There is no information in the literature regarding the teratogenic or carcinogenic effects of stannous chloride or fluoride.
Limited studies on stannous salts demonstrate a weak potential for mutagenicity.
Radiation dosimetry
Absorbed radiation dose estimates following intravenous injection of technetium [99mTc] as colloid are given from ICRP Publication 53. These provide values for three liver conditions:
(i) Normal
(ii) Early to intermediate diffuse parenchymal disease
(iii) Intermediate to advanced diffuse parenchymal disease
Technetium [99mTc] disintegrates with the emission of gamma radiation with an energy of 140keV and a half life of 6 hours to technetium [99mTc] which can be regarded as quasi stable.
(i) Normal liver
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
1.0E-02 |
1.5E-02 |
2.1E-02 |
2.8E-02 |
4.2E-02 |
|
Bladder wall |
1.1E-03 |
1.6E-03 |
2.8E-03 |
5.7E-03 |
9.5E-03 |
|
Bone surfaces |
6.4E-03 |
8.4E-03 |
1.3E-02 |
2.2E-02 |
4.6E-02 |
|
Breast GI-tract |
2.7E-03 |
2.7E-03 |
4.6E-03 |
7.3E-03 |
1.3E-02 |
|
Stomach wall |
6.2E-03 |
8.3E-03 |
1.3E-02 |
2.1E-02 |
3.5E-02 |
|
Small intestine |
4.3E-03 |
5.1E-03 |
9.0E-03 |
1.4E-02 |
2.5E-02 |
|
ULI wall |
5.6E-03 |
6.9E-03 |
1.2E-02 |
2.1E-02 |
3.4E-02 |
|
LLI wall |
1.8E-03 |
2.2E-03 |
3.8E-03 |
6.1E-03 |
1.1E-02 |
|
Kidneys |
9.7E-03 |
1.1E-02 |
1.7E-02 |
2.4E-02 |
3.5E-02 |
|
Liver |
7.4E-02 |
9.2E-02 |
1.4E-01 |
1.9E-01 |
3.4E-01 |
|
Lungs |
5.5E-03 |
7.5E-03 |
1.0E-02 |
1.5E-02 |
2.5E-02 |
|
Ovaries |
2.2E-03 |
2.9E-03 |
4.9E-03 |
7.9E-03 |
1.4E-02 |
|
Pancreas |
1.2E-02 |
1 .7E-02 |
2.5E-02 |
3.7E-02 |
5.9E-02 |
|
Red marrow |
1.1E-02 |
1.5E-02 |
2.3E-02 |
3.8E-02 |
7.2E-02 |
|
Spleen |
7.7E-02 |
1.1E-01 |
1.6E-01 |
2.5E-01 |
4.5E-01 |
|
Testes |
6.2E-04 |
7.6E-04 |
1.3E-03 |
2.2E-03 |
4.5E-03 |
|
Thyroid |
7.9E-04 |
1.2E-03 |
2.0E-03 |
3.5E-03 |
6.5E-03 |
|
Uterus |
1.9E-03 |
2.5E-03 |
4.4E-03 |
7.4E-03 |
1.3E-02 |
|
Other tissue |
2.8E-03 |
3.4E-03 |
4.9E-03 |
7.3E-03 |
1.3E-02 |
|
Effective dose equivalent (mSv/MBq) |
1.4E-02 |
1.8E-02 |
2.8E-02 |
4.1E-02 |
7.3E-02 |
In normal liver function, the effective dose equivalent resulting from an administered activity of 185MBq technetium [99mTc] colloidal tin is 2.6mSv.
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) |
|
Adrenals |
9.9E-03 |
|
Bladder wall |
1.4E-03 |
|
Bone surfaces |
8.2E-03 |
|
Breast |
2.6E-03 |
|
GI-tract | |
|
Stomach wall |
8.1E-03 |
|
Small intestine |
4.4E-03 |
|
ULI wall |
5.3E-03 |
|
LLI wall |
2.4E-03 |
|
Kidneys |
1.1E-02 |
|
Liver |
4.0E-02 |
|
Lungs |
5.2E-03 |
|
Ovaries |
2.7E-03 |
|
Pancreas |
1.5E-02 |
|
Red marrow |
1.5E-02 |
|
Spleen |
1.0E-01 |
|
Testes |
8.6E-04 |
|
Thyroid |
1.0E-03 |
|
Uterus |
2.4E-03 |
|
Other tissues |
3 .0E-03 |
|
Effective | |
|
dose equivalent |
1.4E-02 |
|
(mSv/MBq) |
In early to intermediate diffuse parenchymal disease, the effective dose equivalent resulting from an administered activity of 185MBq technetium [99mTc] colloidal tin is 2. 6mSv.
(iii) Intermediate to advanced diffuse parenchymal disease
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) |
|
Adrenals |
9.8E-03 |
|
Bladder wall |
1.6E-03 |
|
Bone surfaces |
1.2E-02 |
|
Breast |
2.4E-03 |
|
GI-tract | |
|
Stomach wall |
9.8E-03 |
|
Small intestine |
4.6E-03 |
|
ULI wall |
4.9E-03 |
|
LLI wall |
3.1E-03 |
|
Kidneys |
1.1E-02 |
|
Liver |
4.2E-02 |
|
Lungs |
4.8E-03 |
|
Ovaries |
3.3E-03 |
|
Pancreas |
1.8E-02 |
|
Red marrow |
2.3E-02 |
|
Spleen |
1.4E-01 |
|
Testes |
9.5E-04 |
|
Thyroid |
1.1E-03 |
|
Uterus |
2.8E-03 |
|
Other tissues |
3.1E-03 |
|
Effective | |
|
Dose equivalent (mSv/MBq) |
1.7E-02 |
In intermediate to advanced diffuse parenchymal disease, the effective dose equivalent resulting from an administered activity of 185MBq technetium [99mTc] colloidal tin is 3.1mSv.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium fluoride Poloxamer 188
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.
The technetium-99m labelling reaction involved in preparing technetium-99m colloidal tin depends on the maintenance of some tin in the divalent state. This is why the presence of oxidizing agents in the Sodium Pertechnetate (99mTc) Injection may adversely affect the quality of the prepared agent.
Also the presence of water soluble complexants in certain syringes has been found to impair scan quality by the formation of a kidney localising technetium-99m complex.
The presence of aluminium ion in technetium generator eluates may induce flocculation of colloid with subsequent uptake in lungs.
6.3 Shelf life
78 weeks from the day of manufacture.
The reconstituted product should be stored below 25° C. Do not freeze.
The labelled product must be injected within 6 hours of reconstitution.
6.4 Special precautions for storage
Store below 25°C.
Storage should be in accordance with national regulations for radioactive material.
6.5 Nature and contents of container
10ml Type I Ph. Eur., clear, colourless, borosilicate glass vial sealed with a chlorobutyl rubber closure and oversealed with an aluminium overseal with a blue flip off cap.
Pack size: kit contains 5 multidose vials.
6.6 Special precautions for disposal
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 conditions specified by the local competent authority. Contaminated material must be disposed of as radioactive waste via an authorised route.
MARKETING AUTHORISATION HOLDER
7
MEDIAM
85 rue Nelson Mandela
59120 Loos
France
8 MARKETING AUTHORISATION NUMBER(S)
PL 22879/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 30 July 1997 Date of last renewal: 26 March 2007
10 DATE OF REVISION OF THE TEXT
20/12/2010
11 DOSIMETRY (IF APPLICABLE)
Absorbed radiation dose estimates following intravenous injection of technetium-99m as colloid are given. These provide values for three liver conditions:
(1) Normal
(2) Early to intermediate diffuse parenchymal disease
The table below show the dosimetry as calculated according to the Publication 80 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals, Pergamon Press 1998).
(1) Normal liver
|
Organ |
per |
Absorbed dose unit activity administered (mGy/MBq) | |||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
1.2E-02 |
1.5E-02 |
2.1E-02 |
2.8E-02 |
4.2E-02 |
|
Bladder |
1.1E-03 |
1.6E-03 |
2.7E-03 |
5.7E-03 |
9.4E-03 |
|
Bone surfaces |
8.7E-03 |
1.1E-02 |
1.8E-02 |
3.0E-02 |
6.9E-02 |
|
Brain |
6.7E-04 |
8.8E-04 |
1.3E-03 |
2.1E-03 |
4.1E-03 |
|
Breast |
2.1E-03 |
2.7E-03 |
4.6E-03 |
7.2E-03 |
1.3E-02 |
|
Gall bladder GI-tract |
2.0E-02 |
2.3E-02 |
3.1E-02 |
5.0E-02 |
8.4E-02 |
|
Stomach |
6.4E-03 |
8.2E-03 |
1.3E-02 |
2.1E-02 |
3.5E-02 |
|
SI |
4.0E-03 |
5.1E-03 |
8.9E-03 |
1.4E-02 |
2.4E-02 |
|
Colon |
3.8E-03 |
4.8E-03 |
8.5E-03 |
1.5E-02 |
2.4E-02 |
|
(ULI wall |
5.5E-03 |
6.8E-03 |
1.2E-02 |
2.1E-02 |
3.4E-02) |
|
(LLI wall |
1.6E-03 |
2.2E-03 |
3.8E-03 |
6.1E-03 |
1.1E-02) |
|
Heart |
6.5E-03 |
8.3E-03 |
1.2E-02 |
1.7E-02 |
3.0E-02 |
|
Kidneys |
9.5E-03 |
1.2E-02 |
1.7E-02 |
2.4E-02 |
3.5E-02 |
|
Liver |
7.1E-02 |
9.1E-02 |
1.3E-01 |
1.9E-01 |
3.4E-01 |
|
Lungs |
5.9E-03 |
7.5E-03 |
1.0E-02 |
1.5E-02 |
2.5E-02 |
|
Muscle |
2.7E-03 |
3.4E-03 |
4.9E-03 |
7.2E-03 |
1.3E-02 |
|
Oesophagus |
2.1E-03 |
2.7E-03 |
3.7E-03 |
5.7E-03 |
9.8E-03 |
|
Ovaries |
2.2E-03 |
2.9E-03 |
4.9E-03 |
7.9E-03 |
1.4E-02 |
|
Pancreas |
1.3E-02 |
1.7E-02 |
2.5E-02 |
3.7E-02 |
5.9E-02 |
|
Red marrow |
1.1E-02 |
1.2E-02 |
1.9E-02 |
3.2E-02 |
6.4E-02 |
|
Skin |
1.3E-03 |
1.6E-03 |
2.5E-03 |
4.0E-03 |
7.6E-03 |
|
Spleen |
7.5E-02 |
1.1E-01 |
1.6E-01 |
2.4E-01 |
4.3E-01 |
|
Testes |
5.6E-04 |
7.7E-04 |
1.3E-03 |
2.3E-03 |
4.5E-03 |
|
Thymus |
2.1E-03 |
2.7E-03 |
3.7E-03 |
5.7E-03 |
9.8E-03 |
|
Thyroid |
9.3E-04 |
1.2E-03 |
2.0E-03 |
3.5E-03 |
6.5E-03 |
|
Uterus |
1.9E-03 |
2.5E-03 |
4.4E-03 |
7.3E-03 |
1.4E-02 |
|
Remaining organs |
2.7E-03 |
3.4E-03 |
4.9E-03 |
7.1E-03 |
1.2E-02 |
|
Effective dose (mSv/MBq) |
9.4E-03 |
1.2E-02 |
1.8E-02 |
2.8E-02 |
5.0E-02 |
In normal liver function, the effective dose resulting from an administered activity of 185 MBq technetium-99m colloidal tin is 1.74 mSv.
The tables below show the dosimetry as calculated according to the Publication 53 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals, Pergamon Press 1987).
(2) Early to intermediate diffuse parenchymal liver disease
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) |
|
Adrenals |
9.9E-03 |
|
Bladder wall |
1.4E-03 |
|
Bone surfaces |
8.2E-03 |
|
Breast |
2.6E-03 |
|
GI tract | |
|
Stomach wall |
8.1E-03 |
|
Small intestine |
4.4E-03 |
|
ULI wall |
5.3E-03 |
|
LLI wall |
2.4E-03 |
|
Kidneys |
1.1E-02 |
|
Liver |
4.0E-02 |
|
Lungs |
5.2E-03 |
|
Ovaries |
2.7E-03 |
|
Pancreas |
1.5E-02 |
|
Red marrow |
1.5E-02 |
|
Spleen |
1.0E-01 |
|
Testes |
8.6E-04 |
|
Thyroid |
1.0E-03 |
|
Uterus |
2.4E-03 |
|
Other tissue |
3.0E-03 |
|
Effective | |
|
dose equivalent |
1.4E-02 |
|
(mSv/MBq) |
In early to intermediate diffuse parenchymal disease, the effective dose equivalent resulting from an administered activity of 185 MBq technetium-99m colloidal tin is 2.6 mSv.
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | |
|
Adrenals |
9 |
8E-03 |
|
Bladder wall |
1 |
6E-03 |
|
Bone surfaces |
1 |
2E-02 |
|
Breast |
2 |
4E-03 |
|
GI tract | ||
|
Stomach wall |
9 |
8E-03 |
|
Small intestine |
4 |
6E-03 |
|
ULI wall |
4 |
9E-03 |
|
LLI wall |
3 |
1E-03 |
|
Kidneys |
1 |
1E-02 |
|
Liver |
4 |
2E-02 |
|
Lungs |
4 |
8E-03 |
|
Ovaries |
3 |
3E-03 |
|
Pancreas |
1 |
8E-02 |
|
Red marrow |
2 |
3E-02 |
|
Spleen |
1 |
4E-01 |
|
Testes |
9 |
5E-04 |
|
Thyroid |
1 |
1E-03 |
|
Uterus |
2 |
8E-03 |
|
Other tissue |
3.1E-03 | |
|
Effective dose equivalent (mSv/MBq) |
1.7E-02 | |
In intermediate to advanced diffuse parenchymal disease, the effective dose equivalent resulting from an administered activity of 185 MBq technetium-99m colloidal tin is 3.1mSv.
12 INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)
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.