Informations for option: Angiocis, show other option

Select option:

1. Angiocis
2. Angiocis

ANGIOCIS®

Kit for the preparation of stannous pyrophosphate used for the labelling of Red Blood Cells with [^99mTc] Technetium

USER PACKAGE LEAFLET

IDENTIFICATION OF THE MEDICINAL PRODUCT

Name of the medicinal product

ANGIOCIS®

Kit for the preparation of stannous pyrophosphate used for the labelling of Red Blood Cells with [^99mTc] Technetium.

Qualitative and quantitative composition

The kit for the preparation of stannous pyrophosphate used for the labelling of Red Blood Cells with [^99mTc] Technetium consists of five vials containing under nitrogen atmosphere the sterile, pyrogen-free, freeze-dried product with the following composition :

Sodium pyrophosphate decahydrate : 20.12 mg Stannous chloride dihydrate    :    4.05 mg

Concentrated hydrochloric acid : sufficient quantity to make

pH 5.0 - 7.0

The product contains no antimicrobial preservative.

Nature and content of the container

15 ml colourless, European Pharmacopoeia type I, drawn glass vial, closed with a grey rubber stopper and an aluminium capsule.

Pharmaceutical form

Powder for injection.

Pharmaco-therapeutic group Radiopharmaceutical preparation for diagnostic use.

Name and address of the marketing authorization 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

Marketing authorisation n° : PL/11876/0010

Name and adress of the manufacturer

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

- PHARMACODYNAMIC PROPERTIES

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.

PHARMACOKINETIC PROPERTIES

Intravanous 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 %.

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.

- 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.

There are no studies describing possible effects on reproduction or tumor incidence.

- DOSIMETRY

Technetium [^99mTc] decays with the emission of gamma radiation with energy of 140 keV and a half life of 6 hours to technetium [⁹⁹Tc] which can be regarded as quasi stable.

In man whose red blood cells have been labelled by [^99mTc]-pyrophosphate, the radiation doses absorbed are as follows (ICPR 53 - 1988) :

[^99mTc]-LABELLED ERYTHROCYTES Absorbed dose per unit activity administered (mGy/MBq)

Organ	Adult	15 years	10 years	5 years	1 year
Adrenals	8.7E-03	1.1E-02	1.7E-02	2.7E-02	4.9E-02
Bladder wall	9.2E-03	1.2E-02	1.7E-02	2.5E-02	4.6E-02
Bone surfaces	9.2E-03	1.3E-02	2.3E-02	3.9E-02	7.8E-02
Breast	4.3E-03	4.5E-03	7.2E-03	1.1E-02	1.9E-02
GI-tract
Stomach wall	4.8E-03	6.1E-03	9.5E-03	1.4E-02	2.4E-02
Small intestine	4.4E-03	5.3E-03	8.1E-03	1.2E-02	2.2E-02
ULI wall	4.3E-03	5.5E-03	7.9E-03	1.3E-02	2.1E-02
LLI wall	3.9E-03	5.3E-03	8.0E-03	1.1E-02	2.1E-02
Heart	2.3E-02	2.8E-02	4.1E-03	6.2E-02	1.1E-01
Kidneys	1.0E-02	1.2E-02	1.9E-02	3.0E-02	5.5E-02
Liver	7.5E-03	8.8E-03	1.4E-02	2.1E-02	3.8E-02
Lungs	1.4E-02	1.8E-02	2.9E-02	4.5E-02	8.5E-02
Ovaries	4.2E-03	5.4E-03	7.9E-03	1.2E-02	2.1E-02
Pancreas	6.2E-03	7.5E-03	1.1E-02	1.7E-02	2.9E-02
Red marrow	7.3E-03	8.8E-03	1.3E-02	2.0E-02	3.5E-02
Spleen	1.5E-02	1.8E-02	2.8E-02	4.4E-02	8.4E-02
Testes	2.7E-03	3.7E-03	5.4E-03	8.3E-03	1.5E-02
Thyroid	4.9E-03	7.1E-03	1.2E-02	1.9E-02	3.5E-02
Uterus	4.7E-03	5.7E-03	8.5E-03	1.3E-02	2.2E-02
Other tissue	3.7E-03	4.4E-03	6.4E-03	9.8E-03	1.8E-02
Effective dose equivalent (mSv/MBq)	8.5E-03	1.1E-02	1.6E-02	2.5E-02	4.6E-02

For blood pool scintigraphy the effective dose equivalent resulting of an administrated dose of 925 MBq is 7.9 mSv (per 70 kg individual) and the typical radiation dose to the critical organ (heart) is 21 mGy.

DIAGNOSTIC INDICATIONS

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.

- NECESSARY INFORMATION BEFORE TAKING THE MEDICINAL PRODUCT

Contra-indications

None.

Special warnings and special precautions for use

Special warning

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.

Special precautions for use

Radiopharmaceutical agents should only be used by qualified personnel with appropriate government authorisation for the use and manipulation of radionuclides.

This radiopharmaceutical may be received, used and administered only by authorized persons in hospitals. Its receipt, storage, transfer and disposal are subject to the regulations and the appropriate licenses of the local competent official organisations.

Radiopharmaceutical intended for administration to patients should be prepared by the user in a manner which satisfies both radiological safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken, complying with the requirements of Good Pharmaceutical Manufacturing Practices.

In infants and children, a particularly careful assessment must be made of the diagnostic value, necessity for and risks of the procedure.

Interactions with other medicinal products and other forms of interactions

Reduction in red blood cell labelling yield has been reported with heparin, tin overload, aluminium, prazosin, methyldopa, hydralazin, digitalic related compounds, quinidine,    p-adrenergic    blockers

(e.g. propranolol), calcium channel blockers (e.g. verapamil, nifedipine), nitrates (e.g. nitroglycerin), anthracycline antibiotic, iodinated contrast agents and Teflon catheter (The Sn++ can react with the catheter).

Use during pregnancy and lactation

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 to the mother and the foetus. Administration of 925 MBq results in an absorbed dose to the uterus of 4.3 mGy. Doses above 0.5 mGy should be regarded as a potential risk to 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 the mother has ceased breast feeding and as to whether the most appropriate choice of radiopharmaceutical has been made. If the administration is considered necessary, breast feeding should be interrupted and the expressed feeds discarded. Breast feeding can be restarted about 12 hours post injection or breast feeding can be restarted when the level in milk will not result in a radiation dose greater than 1 mSv to the child.

Effects on ability to drive and use machines

Effects on ability to drive and use machines have not been described.

List of excipients

Stannous chloride dihydrate Concentrated hydrochloric acid Nitrogen

Incompatibilities

None known to date.

- NECESSARY AND USUAL INSTRUCTIONS FOR PROPER USE Posology and method of administration

Administration is by intravenous injection.

Red Blood Cell (RBC) labelling methods

The stannous pyrophosphate lyophilisate (non radioactive substance) is first reconstituted with isotonic sodium chloride solution for injection.

In vivo method :

Injection of the reconstituted solution of the stannous pyrophosphate complex and consecutive injection [^99mTc] pertechnetate 30 minutes later.

Posology

Blood pool scintigraphy

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).

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 :

Error! X 1.5

Scanning can be started immediately after injection of the tracer. Pediatric doses

The activity for children may be calculated from the recommended range of adult activity and adjusted according to body weight or surface area.

However the Paediatric Task Group of EANM recommends to calculate the administered activity from the body weight according to the following table.

Fraction of adult dose

In very young children (up to 1 year) a minimum dose of 80 MBq is necessary in order to obtain images of sufficient quality.

Because of the long lasting fixation of stannous salts on red blood cells, it is recommended not to repeat the procedure before 3 months.

Instructions for use

Method of preparation

Usual precautions regarding sterility and radioprotection should be respected.

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 :

Error! X 1.5

Thirty minutes after the injection, 740 to 925 MBq (20 to 25 mCi) of [^99mTc] sodium pertechnetate solution are administered intravenously.

The examination can then begin immediately.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill or urine, vomiting, etc. Suitable precautions should be taken concerning the radioactivity eliminated by the patients in order to avoid any contamination. Radiation protection precautions in accordance with national regulations must therefore be taken.

The residues may be put in an ordinary waste bin sofar as long as the activity of vials and syringes does not exceed that of background when measured with a low level radiation detector. Waste must be disposed of according to national regulations.

Overdose

In the event of the accidental administration of an overdose of the radiopharmaceutical 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.

- UNDESIRABLE EFFECTS

For each patient, exposure to ionising 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 intented 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 radiation dose delivered (EDE) is less than 20 mSv. Higher doses may be justified in some clinical circumstances.

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, urticaria, generalized prutitus, cardiac arrhythmia, facial edema and coma have been reported.

- EXPIRY DATE

The expiry date for this product is 12 months from the day of manufacture.

The reconstituted product should be used within 6 hours after reconstitution.

Special precautions for storage

The kit should be stored at a temperature ranging between +2 °C and +8 °C.

The reconstituted product should be stored under refrigeration.

- DATE OF REVISION OF TEXT

04/2006

Kit for the preparation of stannous pyrophosphate used for the labelling of Red Blood Cells with ["^mTc] Technetium

PATIENT INFORMATION LEAFLET

1. IDENTIFICATION OF THE MEDICINAL PRODUCT

Name of the Medicinal Product

ANGIOCIS®

Kit for the preparation of stannous pyrophosphate used for the labelling of Red Blood Cells with [^99mTc] Technetium.

Qualitative Composition

Sodium pyrophosphate decahydrate.

Quantitative Composition

Each vial contains 20.12 mg of sodium pyrophosphate decahydrate. Pharmaceutical Form

Powder for injection.

Pharmaco-Therapeutic Group

This product is used in the preparation of a diagnostic radiopharmaceutical. When injected, the radiopharmaceutical temporarily collects on red blood cells. Because the substance contains a small amount of radioactivity, it can be detected from outside the body using special cameras, and pictures, known as scans, can be taken. These scans will show exactly the distribution of the radiopharmaceutical within heart cavity, aorta, large artery and vein pathways and will help to determine he heart function.

CIS bio international B.P. 32

91192 Gif-sur-Yvette Cedex FRANCE

PL/11876/0010

Name and Address of the Manufacturer

CIS bio international B.P. 32

91192 Gif-sur-Yvette Cedex FRANCE

2. DIAGNOSTIC INDICATIONS

ANGIOCIS is used to label red blood cells in order :

-    to perform scans of the heart and to determine your heart function,

-    to detect organ perfusion and vascular abnormalities imaging,

-    to localise occult gastro-intestinal bleeding.

3. WARNINGS

When should this Product not be used ?

Because the ANGIOCIS must not be administered to pregnant women or during lactation, you should tell your physician, if there is any possibility that you are pregnant.

Any possibility of pregnancy must be ruled out before using this product.

IN CASE OF DOUBT IT IS ESSENTIAL TO CONSULT YOUR PHYSICIAN. Special Warnings

The use of ANGIOCIS does involve administration of small amounts of radioactivity. The risk this involves is very small and your physician will not consider carrying out the investigation unless he believes that the risk is outweighed by the potential benefit of the study.

Precautions for Use

ANGIOCIS is administered by intravenous route by people who are trained and qualified in the safe handling of radioactive material.

Your physician will inform you if you need to take any special precaution before or after the administration of the product.

IN CASE OF DOUBT DO NOT HESITATE TO CONSULT YOUR PHYSICIAN.

Interaction with other Medicinal Products and other Forms of Interaction

Some drugs may affect the quality of the images.

IN ORDER TO AVOID POSSIBLE INTERACTIONS WITH OTHER MEDICINAL PRODUCTS, ANY OTHER CURRENT MEDICATION MUST BE NOTIFIED TO YOUR PHYSICIAN.

Pregnancy-Lactation

The preparation may not be administered to pregnant women.

During the lactation, your physician will only use this product if he considers that the benefit outweighs the risk. Breast-feeding should be interrupted before the administration. Your physician will tell you when you could restart it.

Effects on Ability to Drive or to Operate Machinery

Effects on the ability to drive and use machines are not expected.

Sportsmen and Sportswomen

There are no particular precautions for the use of ANGIOCIS by people engaged in active sport.

List of those Excipients, Knowledge of which is important for the Safe Use of the Medicinal Product in certain Patients

There is no excipients, knowledge of which is important for the safe use of the Medicinal Product in certain patients.

4. HOW IS THIS PRODUCT USED ?

Dosage

Your physician will decide on the amount of radioactive ANGIOCIS to be used.

For a 70 kg adult, the average radioactivity administered is between 740 to 925 MBq. Lower doses are used for children.

Method and Route of Administration

The ANGIOCIS is intravenously injected in two injections :

First : injection of the Sn pyrophosphate.

Second : thirty minutes after the first injection, intravenous administration of Sodium [^99mTc] pertechnetate.

Frequency of Administration and Appropriate Time of Administration

Two injections separated by thirty minutes.

The scans may be started immediately after the second injection.

Action to be taken in the case of an Overdose

Since ANGIOCIS is administered by a physician under strictly controlled conditions there is few question of possible radiation overdose.

In any case, elimination of ANGIOCIS is entirely dependants on the normal haemolytic process.

Action to be taken when one or more doses have not been taken

Not applicable in the case of this medicinal product.

Risk of withdrawal effects No such risks occur with this product.

5. UNDESIRABLE EFFECTS

Some cases of allergic type reactions have been reported after administration of both the unlabelled Sn-pyrophosphate and the Tc99m pertechnetate. (1 to 5 per 100.000 uses).

INFORM YOUR PHYSICIAN IF YOU EXPERIENCE ANY ILL-EFFECTS.

6. STORAGE

The product label includes the appropriate storage conditions and the expiry date for the batch of the product. Hospital personnel will ensure that the product is stored correctly and not administered to you after the stated expiry date.

7. DATE OF LAST REVISION OF THE PACKAGE LEAFLET

04/2006

T0709pC

03.04.06

4