Angiocis
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
ANGIOCIS 20 mg kit for radiopharmaceutical preparation.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains 20.12 mg of sodium pyrophosphate decahydrate.
The radionuclide is not part of the kit.
Excipients with known effect: sodium.
Each vial contains 4.15 mg of sodium.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Kit for radiopharmaceutical preparation.
White pellet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
After reconstitution with isotonic sodium chloride solution for injection, the stannous pyrophosphate complex, used in combination with (99mTc) pertechnetate, is indicated for in vivo red blood cell labelling for blood pool scintigraphy.
Major indications are:
- Angiocardioscintigraphy for:
• evaluation of ventricular ejection fraction,
• evaluation of global and regional cardiac wall motion,
• myocardial phase imaging.
- Organ perfusion and vascular abnormalities imaging.
- Diagnosis and localisation of occult gastro-intestinal bleeding.
4.2 Posology and method of administration
This medicinal product is intended for use in designated nuclear medicine facilities only, and should only be handled by authorised personnel.
Posology
Blood pool scintigraphy Adults
The optimal amount of nonradioactive stannous tin for preparation of Red Blood Cells in vivo is 0.05 pg to 1.25 pg per mL of the total blood volume of the patient (near 5 000 mL in a man of 70 kg weight).
Sodium (99mTc) pertechnetate should be injected (in vivo) after 30 minutes. The average activity administered by single injection after in vivo labelling is 890 MBq (740-925 MBq).
Paediatric population
The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and to adolescents may be calculated according to the recommendations of the Paediatric Task Group of the EANM (1990). The activity to be administered to a child should be calculated from the body weight according to the following table:
Fraction of adult dose
|
3 |
kg = |
0.1 |
22 |
kg = |
0.50 |
42 |
kg = |
0 |
78 |
|
4 |
kg = |
0.14 |
24 |
kg = |
0.53 |
44 |
kg = |
0 |
80 |
|
6 |
kg = |
0.19 |
26 |
kg = |
0.56 |
46 |
kg = |
0 |
82 |
|
8 |
kg = |
0.23 |
28 |
kg = |
0.58 |
48 |
kg = |
0 |
85 |
|
10 |
kg = |
0.27 |
30 |
kg = |
0.62 |
50 |
kg = |
0 |
88 |
|
12 |
kg = |
0.32 |
32 |
kg = |
0.65 |
52-54 |
kg = |
0 |
90 |
|
14 |
kg = |
0.36 |
34 |
kg = |
0.68 |
56-58 |
kg = |
0 |
92 |
|
16 |
kg = |
0.40 |
36 |
kg = |
0.71 |
60-62 |
kg = |
0 |
96 |
|
18 |
kg = |
0.44 |
38 |
kg = |
0.73 |
64-66 |
kg = |
0 |
98 |
|
20 |
kg = |
0.46 |
40 |
kg = |
0.76 |
68 |
kg = |
0 |
99 |
In very young children (up to 1 year) a minimum dose of 80 MBq is necessary in order to obtain images of sufficient quality.
Method of administration
Multidose use.
This medicinal product should be reconstituted before administration to the patient.
Administration is by intravenous injection.
Red Blood Cell (RBC) labelling method (in vivo method)
Injection of the reconstituted solution of the stannous pyrophosphate complex and consecutive injection (99mTc) pertechnetate 30 minutes later.
For instructions on reconstitution of the medicinal product before administration, see section 12.
For patient preparation, see section 4.4.
Image acquisition
Scanning can be started immediately after injection of the tracer.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the components of the radiopharmaceutical.
4.4 Special warnings and precautions for use
Potential for hypersensitivity or anaphylactic reactions
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.
Individual benefit/risk justification
For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.
Paediatric population
For information on the use in paediatric population, see sections 4.2.
Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).
Patient preparation
The patient should be well hydrated before the start of the examination and urged to void as ofter as possible during the first hours after the examination in order to reduce radiation.
Specific warnings
It is recommended that in vivo (99mTc) RBC labelling be performed prior to administration of iodinated contrast media. Otherwise, labelling efficiency will be adversely affected.
Because of the long lasting fixation of stannous salts on red blood cells, it is recommended not to repeat the procedure before 3 months.
This medicinal product contains less than 1 mmol of sodium (23 mg) per vial, i.e. is essentially ‘sodium- free’.
Precautions with respect to environmental hazard see section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
Reduction in red blood cell labelling yield has been reported with:
- heparin
- tin overload
- aluminium
- prazosin
- methyldopa
- hydralazine
- digitalic related compounds
- quinidine
- P-adrenergic blockers (e.g. propanolol)
- calcium channel blockers (e.g. verapamil, nifedipine)
- nitrates (e.g. nitroglycerin)
- anthracycline antibiotic
- iodinated contrast agents
- Teflon catheter (The Sn++ can react with the catheter).
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.
Pregnancy
Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus. Administration of 925 MBq results in an absorbed dose to the uterus of
3.6 mGy.
Breast-feeding
Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for at least 12 hours and the expressed feeds discarded.
4.7 Effects on ability to drive and use machines
Effects on ability to drive and use machines have not been described.
4.8 Undesirable effects
Adverse reactions after the intravenous administration of both the unlabelled and the technetium-99m complexes have been reported in isolated cases (1-5 per 100.000 uses). The following effects have been described: flush; headache, vasodilatation, nausea, dizziness, swelling of the arm, erythema and itching at the injection site, diaphoresis and tinnitus, urticarial, generalized prutitus, cardiac arrhythmia, facial edema and coma have been reported.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects.
As the effective dose is 6.5 mSv when the maximal recommended activity of 925 MBq is administered these adverse reactions are expected to occur with a low probability.
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 the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard.
4.9 Overdose
In the event of administration of an overdose with stannous pyrophosphate, very little supportive treatment can be undertaken since its elimination is entirely dependant on the normal haemolytic process.
Forced diuresis and frequent bladder voiding are recommended in the case of overdosage with (99mTc) pertechnetate.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Diagnostic Radiopharmaceuticals, ATC code: V09GA06
At doses used for diagnostic procedures, neither stannous pyrophosphate, sodium (99mTc) pertechnetate nor stannous pyrophosphate (99mTc) nor labelled Red Blood Cells appear to exert any pharmacodynamic effects.
5.2 Pharmacokinetic properties
Organ uptake
Intravenous injection of stannous salts induces a "stannous loading" of erythrocytes. Subsequent sodium (99mTc) pertechnetate injection results in an accumulation and a retention of sodium (99mTc) pertechnetate in the choroid plexus and red blood cells. Intravenous administration of 10-20 pg stannous ion/kg body weight (in form of stannous pyrophosphate) followed 30 minutes later by 370-740 MBq pertechnetate injection results in efficient labelling of blood pool. Under normal circumstances intravenously injected pertechnetate freely diffuses into and out from the erythrocytes. However, when the erythrocytes have been preloaded with stannous ion, the sodium (99mTc) pertechnetate is reduced within the cells and becomes bound to the chains of the globin. The mechanisms by which sodium (99mTc) pertechnetate becomes attached to tin primed red blood cells are not clearly understood. However 20 % of injected pertechnetate enters the red cell and binds to a beta chain of globin.
While the remaining 70-80 % of pertechnetate is believed to be located in the cytoplasm or on the red cell membrane. On the other hand reducing the surface charge of the erythrocytes decreases the efficiency of labelling down to 20 %.
Distribution
The most beneficial time for the injection of (99mTc) pertechnetate for the in vivo labelling is 20-30 min after the administration of pyrophosphate.
At 10 and 100 minutes post injection. 77 ± 15 % and 71 ± 14 % respectively of the injected activity is found in the blood. This value remains constant for about 2 hours after injection with only about 6 % decrease in total blood radioactivity during this period.
Up to eight days after the examination, labelling of erythrocytes with (99mTc) pertechnetate may still be observed. There is no appreciable effect with doses of up to 0.02 mg of tin/kg.
5.3 Preclinical safety data
There are no preclinical safety data specific to technetium labelled erythrocytes. The toxicity of pertechnetate ion and stannous salts has been studied and reported in the literature. Systemic toxical effects are only observed at relatively high parenteral doses. giving a safety ratio of at least 150.
Repeated dose toxicity studies in rats with 50-100 times human dose do not cause macroscopic or microscopic alterations.
Stannous salts are reported to have a weak potential for mutagenicity.
Mutagenicity studies and long-term carcinogenicity studies have not been carried out.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Stannous chloride dihydrate Concentrated hydrochloric acid
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.
6.3 Shelf life 1 year.
After reconstitution: store in a refrigerator (2 °C - 8 °C) and use within 6 hours.
6.4 Special precautions for storage
Store the kit in a refrigerator (2 °C - 8 °C).
For storage conditions after reconstitution of the medicinal product, see section 6.3. Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
6.5 Nature and contents of container
15 mL colourless, European Pharmacopoeia type I, drawn glass vial, closed with a grey rubber stopper and an aluminium capsule.
6.6 Special precautions for disposal
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.
Content of the vial is intended only for use in the preparation of stannous pyrophosphate and is not to be administered directly to the patient without first undergoing the preparative procedure.
For instructions on extemporaneous preparation of the medicinal product before administration, see section 12.
If at any time in the preparation of this product the integrity of this vial 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 content of the vial is not radioactive. However, when sodium pertechnetate (99mTc), Ph. Eur.] is injected, adequate shielding must be maintained.
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.
The residues may be put in an ordinary waste bin as long as the activity of vials and syringes does not exceed that of background when measured with a low level radiation detector.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
CIS bio international B.P. 32
91192 Gif-sur-Yvette Cedex FRANCE
Tel. : +33-(0)1.69.85.70.70 Fax : +33-(0)1.69.85.70.71
8 MARKETING AUTHORISATION NUMBER(S)
PL 11876/0010
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 17 October 1997 Date of latest renewal: 23 March 2011
10 DATE OF REVISION OF THE TEXT
26/11/2015
11 DOSIMETRY
Technetium (99mTc) is produced by means of a (99Mo/99mTc) generator and decays with the emission of gamma radiation with a mean energy of 140 keV and a half life of 6.02 hours to technetium (99Tc) which. in view of its long half-life of 2.13 x 105 years can be regarded as quasi stable.
The data listed below are from ICPR 80. 1998 and are calculated according to the following assumptions:
(99mTc)-LABELLED ERYTHROCYTES
|
Organ |
Absorbed dose per unit activity adminis |
tered (mGy/MBq) | |||
|
Adult |
15 year |
10 year |
5 year |
1 year | |
|
Adrenals |
0.0099 |
0.012 |
0.020 |
0.030 |
0.056 |
|
Bladder |
0.0085 |
0.011 |
0.014 |
0.017 |
0.031 |
|
Bone surfaces |
0.0074 |
0.012 |
0.019 |
0.036 |
0.074 |
|
Brain |
0.0036 |
0.0046 |
0.0075 |
0.012 |
0.022 |
|
Breast |
0.0035 |
0.0041 |
0.0070 |
0.011 |
0.019 |
|
Gall bladder |
0.0065 |
0.0081 |
0.013 |
0.020 |
0.030 |
|
Gastrointestinal-tract : Stomach |
0.0046 |
0.0059 |
0.0097 |
0.014 |
0.025 |
|
Small intestine |
0.0039 |
0.0049 |
0.0078 |
0.012 |
0.021 |
|
Colon |
0.0037 |
0.0048 |
0.0075 |
0.012 |
0.020 |
|
(Upper Large Intestine |
0.0040 |
0.0051 |
0.0080 |
0.013 |
0.022) |
|
(Lower Large Intestine |
0.0034 |
0.0044 |
0.0069 |
0.010 |
0.018) |
|
Heart |
0.023 |
0.029 |
0.043 |
0.066 |
0.11 |
|
Kidneys |
0.018 |
0.022 |
0.036 |
0.057 |
0.11 |
|
Liver |
0.013 |
0.017 |
0.026 |
0.040 |
0.072 |
|
Lungs |
0.018 |
0.022 |
0.035 |
0.056 |
0.11 |
|
Muscles |
0.0033 |
0.0040 |
0.0061 |
0.0094 |
0.017 |
|
Oesophagus |
0.0061 |
0.0070 |
0.0098 |
0.015 |
0.023 |
|
Ovaries |
0.0037 |
0.0048 |
0.0070 |
0.011 |
0.019 |
|
Pancreas |
0.0066 |
0.0081 |
0.013 |
0.019 |
0.033 |
|
Red marrow |
0.0061 |
0.0076 |
0.012 |
0.020 |
0.037 |
|
Skin |
0.0020 |
0.0024 |
0.0038 |
0.0062 |
0.012 |
|
Spleen |
0.014 |
0.017 |
0.027 |
0.043 |
0.081 |
|
Testes |
0.0023 |
0.0030 |
0.0044 |
0.0069 |
0.013 |
|
Thymus |
0.0061 |
0.0070 |
0.0098 |
0.015 |
0.023 |
|
Thyroid |
0.0057 |
0.0071 |
0.012 |
0.019 |
0.036 |
|
Uterus |
0.0039 |
0.0049 |
0.0074 |
0.011 |
0.019 |
|
Remaining organs |
0.0035 |
0.0045 |
0.0073 |
0.013 |
0.023 |
|
Effective dose (mSv/MBq) |
0.0070 |
0.0089 |
0.014 |
0.021 |
0.039 |
For blood pool scintigraphy the effective dose resulting from the administration of an activity of 925 MBq for an adult weighing 70 kg is about 6.5 mSv.
For an administered activity of 925 MBq the typical radiation dose to the critical organ (heart) is 21 mGy.
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
Usual precautions regarding sterility and radioprotection should be respected. Withdrawals should be performed under aseptic conditions. The vial must not be opened. After disinfecting the stopper, the solution should be withdrawn via the stopper using a single dose syringe and a disposable sterile needle.
If the integrity of this vial is compromised, the product should not be used.
Method of preparation
The stannous pyrophosphate lyophilisate (non radioactive substance) is reconstituted with isotonic sodium chloride solution for injection.
Take a vial from the kit and using a hypodermic syringe introduce 3 mL of a sterile and apyrogenic solution of 0.9% sodium chloride through the stopper, without using a breather needle as the contents are under nitrogen.
The blood volume of the patient should be calculated using standard tables, based on height and weight. The volume of reconstituted solution to be injected intravenously can be calculated using the following formula:
Blood volume of patient (mL) x 1.5 5400 mL
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Detailed information on this medicinal product is available on the website of the MHRA.