MIBI RADIOPHARMACY LABORATORY 500 micrograms PHARMACEUTICAL PREPARATION KIT

Introduction

PATIENT INFORMATION LEAFLET

MIBI Radiopharmacy Laboratory 500 micrograms,

Radioactive equipment for radiopharmaceutical preparation EFG

Tetrafluoroborate of [Tetrakis(1-isocyanide-2-methoxy-2-methylpropyl)copper(I)]

This medicinal product is subject to additional monitoring, which will allow for the rapid identification of new safety information. You can help by reporting any side effects you may experience. See the section on how to report side effects at the end of section 4.

Read all of this leaflet carefully before you start using this medicine, as 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 is responsible for supervising the procedure.
• If you experience any side effects, inform your nuclear medicine doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What MIBI Radiopharmacy Laboratory 500 microgramsis and what it is used for
2. What you need to know before you use MIBI Radiopharmacy Laboratory 500 micrograms
3. How to use MIBI Radiopharmacy Laboratory 500 micrograms
4. Possible side effects
5. Storage of MIBI Radiopharmacy Laboratory 500 micrograms
6. Contents of the pack and further information

1. What MIBI Radiopharmacy Laboratory 500 micrograms is and what it is used for

This medicinal product is a radiopharmaceutical for diagnostic use only.

MIBI Radiopharmacy Laboratory 500 microgramscontains a substance called tetrafluoroborate of [tetrakis(1-isocyanide-2-methoxy-2-methylpropyl)copper(I)], which is used to study heart function and blood flow (myocardial perfusion) by performing a heart image (scintigraphy), for example to detect heart attacks (myocardial infarction) or when a disease causes a reduction in blood supply to the entire heart muscle or to a part of it (ischemia). MIBI Radiopharmacy Laboratory 500 microgramsis also used for the diagnosis of cardiac abnormalities, along with other detection methods, when the results are unclear. MIBI Radiopharmacy Laboratory 500 microgramsmay also be used to locate overactive parathyroid glands (glands that secrete the hormone that controls calcium levels in the blood).

Once MIBI Radiopharmacy Laboratory 500 microgramsis injected, it temporarily accumulates in certain parts of the body. This radiopharmaceutical contains a small amount of radioactivity, which can be detected from outside the body using special cameras. Your nuclear medicine doctor will then take an image (scintigraphy) of the organ in question, which can provide valuable information about the structure and function of that organ, or the location of a tumor, for example.

The use of MIBI Radiopharmacy Laboratory 500 microgramsinvolves exposure to small amounts of radioactivity. Your doctor and nuclear medicine doctor have considered that the clinical benefit you may obtain from the procedure using this radiopharmaceutical outweighs the risk due to radiation.

2. What you need to know before you use MIBI Radiopharmacy Laboratory 500 micrograms

MIBI Radiopharmacy Laboratory 500 micrograms must not be used

• if you are allergic to tetrafluoroborate of tetrakis [(1-isocyanide-2-methoxy-2-methylpropyl)copper(I)] or to any of the other components of this medicinal product (listed in section 6).

Warnings and precautions

Be particularly careful with MIBI Radiopharmacy Laboratory 500 micrograms:

• if you are pregnant or think you may be pregnant,
• if you are breast-feeding,
• if you have kidney or liver disease.

You should inform your nuclear medicine doctor in any of the above cases. Your nuclear medicine doctor will tell you if you need to take any special precautions after using this medicinal product. Consult your nuclear medicine doctor if you have any doubts.

Before administration of MIBI Radiopharmacy Laboratory 500 micrograms:

• fast for at least 4 hours when the product is to be used for cardiac imaging,
• drink plenty of water before the start of the examination, in order to urinate frequently during the first hours after the study.

Children and adolescents

Consult your nuclear medicine doctor if you are under 18 years old.

Use of other medicinal products and MIBI Radiopharmacy Laboratory 500 micrograms

There are a number of medicinal products, foods, and drinks that can adversely affect the result of the planned test. Therefore, it is recommended that you consult your doctor about which medicinal products you should stop taking before the test and which ones you should take again after the test. Also, inform your nuclear medicine doctor about any medicinal product you are taking, have recently taken, or may have taken, as they may interfere with the interpretation of the images.

In particular, inform your nuclear medicine doctor about any medicinal product you are taking that may affect heart function and/or blood flow.

Consult your nuclear medicine doctor before taking any medicinal product.

Pregnancy and breast-feeding

You should inform your nuclear medicine doctor before administration of MIBI Radiopharmacy Laboratory 500 microgramsif you are pregnant, think you may be pregnant, or are breast-feeding. In case of doubt, it is important to consult the nuclear medicine doctor in charge of supervising the procedure.

In case of pregnancy,

your nuclear medicine doctor will only administer this medicinal product during pregnancy if they consider that the benefit outweighs the risks.

If you are breast-feeding,

inform your nuclear medicine doctor if you are breast-feeding, as they may ask you to interrupt breast-feeding until there is no longer radioactivity in your body, which occurs after 24 hours. The milk obtained during this period should be discarded. Consult your nuclear medicine doctor about when you can resume breast-feeding.

If you are pregnant, breast-feeding, think you may be pregnant, or plan to become pregnant, consult your nuclear medicine doctor before using this medicinal product.

Driving and using machinery

The influence of MIBI Radiopharmacy Laboratory 500 microgramson the ability to drive and use machinery is considered negligible.

MIBI Radiopharmacy Laboratory 500 micrograms contains sodium

This medicinal product contains less than 1 mmol of sodium (23 mg) per vial, so it is considered essentially 'sodium-free'.

The administration of this medicinal product may contain more than 23 mg of sodium. This should be taken into account if you are on a low-sodium diet. Consult your nuclear medicine doctor.

3. How to use MIBI Radiopharmacy Laboratory 500 micrograms

There is strict legislation regarding the use, handling, and disposal of radiopharmaceuticals. MIBI Radiopharmacy Laboratory 500 microgramswill only be used in specially controlled areas. This product will be handled and administered only by trained and qualified personnel for safe use. These persons will take special care in the safe use of this product and will keep you informed about their actions.

The nuclear medicine doctor supervising the procedure will decide the amount of MIBI Radiopharmacy Laboratory 500 microgramsto be used in your case. It will be the smallest amount possible to obtain the desired information.

Normally, the recommended amount to be administered to an adult varies depending on the test to be performed and ranges from 200 to 2000 MBq (Megabecquerel, the unit used to express radioactivity).

Use in children and adolescents

In children and adolescents, the amount to be administered will be adapted to the child's weight.

Administration of MIBI Radiopharmacy Laboratory 500 micrograms and performance of the procedure

MIBI Radiopharmacy Laboratory 500 microgramsis administered using a vein in the arm or foot (intravenous administration). One or two injections will be sufficient to perform the test your doctor needs.

After the injection, you will be offered a drink and asked to urinate immediately before the test.

Your nuclear medicine doctor will inform you about any special precautions you should take after administration of this medicinal product. Consult your nuclear medicine doctor if you have any doubts.

You will be injected with the prepared solution before image acquisition. The examination will take place 5 or 10 minutes after the injection, or even 6 hours after the injection, depending on the test.

In the case of cardiac tests, two injections may be necessary: one at rest and another after exercise (for example, during physical exercise or with pharmacological induction). The two injections will be spaced at least two hours apart, with no more than 2000 MBq administered in total (one-day protocol). A two-day protocol is also possible.

In scintigraphic tests for breast lesions, an injection of 750 to 1100 MBq will be administered in the vein of the arm opposite the breast in question, or in the foot vein.

For the localization of overactive parathyroid glands, the administered activity will range from 185 to 1100 MBq, depending on the methods used.

If the medicinal product is to be used for cardiac imaging, you will be asked not to ingest any food for at least 4 hours before the test. After the injection, but before acquiring the image (scintigraphy), you will be asked to ingest a light meal in fats, if possible, or to drink one or two glasses of milk, in order to reduce radioactivity in your liver and improve the image.

Duration of the procedure

Your nuclear medicine doctor will inform you about the normal duration of the procedure.

After administration of MIBI Radiopharmacy Laboratory 500 micrograms, you should:

• avoid close contact with children and pregnant women for 24 hours after the injection,
• urinate frequently to eliminate the product from your body.

Your nuclear medicine doctor will inform you about any special precautions you should take after administration of this medicinal product. Consult your nuclear medicine doctor if you have any doubts.

If you have been administered more MIBI Radiopharmacy Laboratory 500 micrograms than you should

Overdose is almost impossible since you will receive a precisely controlled dose of MIBI Radiopharmacy Laboratory 500 microgramsfrom the nuclear medicine doctor supervising the procedure. However, in case of overdose, you will receive the appropriate treatment. In particular, the nuclear medicine doctor in charge of the procedure may recommend that you drink plenty of water to eliminate MIBI Radiopharmacy Laboratory 500 microgramsfrom your body.

If you have any doubts about the use of this medicinal product, consult your nuclear medicine doctor in charge of supervising the procedure.

4. Possible side effects

Like all medicinal products, MIBI Radiopharmacy Laboratory 500 microgramscan cause side effects, although not everybody gets them.

Rarely, allergic reactions such as difficulty breathing, extreme fatigue, nausea (usually during a period of 2 hours after administration), inflammation under the skin that can occur in areas such as the face and legs (angioedema) and obstruct the airways, or cause a dangerous drop in blood pressure (hypotension) and a decrease in heart rate (bradycardia) have been observed. Doctors are aware of this possibility and have emergency treatment available for use in these cases. Local skin reactions such as itching, urticaria, rash, inflammation, and redness have also been rarely detected. If you experience any of the above reactions, contact your nuclear medicine doctor immediately.

Other possible side effects are listed below, in order of frequency:

This radiopharmaceutical will release small amounts of ionizing radiation associated with a minimal risk of cancer and genetic defects.

Information on side effects

If you experience any side effects, inform your nuclear medicine doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects using the national reporting system included in Annex V. By reporting side effects, you can help provide more information on the safety of this medicinal product.

Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es

5. Storage of MIBI Radiopharmacy Laboratory 500 micrograms

You will not need to store this medicinal product, as this is the responsibility of the specialist in suitable locations. The storage of radiopharmaceuticals will be carried out in accordance with national regulations on radioactive materials.

The following information is intended only for specialists.

This medicinal product should not be used after the expiry date stated on the label.

6. Packaging Contents and Other Information

Composition of MIBI Radiopharmacy Laboratory 500 micrograms

• The active ingredient is tetrafluoroborate of [tetrakis[(1-isocyanide-2-methoxy-2-methylpropyl)copper(I)].
• The other ingredients are: Tin(II) chloride dihydrate, Cysteine hydrochloride monohydrate, Sodium pyrophosphate decahydrate, Sodium chloride, Glycine

Appearance of MIBI Radiopharmacy Laboratory 500 micrograms and Packaging Contents

The product consists of a kit for radiopharmaceutical preparation.

MIBI Radiopharmacy Laboratory 500 microgramsconsists of tetrafluoroborate of [tetrakis[(1-isocyanide-2-methoxy-2-methylpropyl)copper(I)], which must be dissolved in a solution and combined with radioactive technetium before use as an injection. Once the radioactive principle pertecnetate sodium (99mTc) is added to the vial, technetium (99mTc) sestamibi is formed. This solution is ready for injection.

Package size:

6 vials

2x6 vials (Clinical packaging)

4x6 vials (Clinical packaging)

Marketing Authorization Holder and Manufacturer

Radiopharmacy Laboratory Ltd.

2040 Budaörs, Gyár u.2.

Hungary

Telephone: +36-23-886-950

Fax: +36-23-886-955

e-mail: info@radiopharmacylab.hu

Manufacturer Responsible:

Medi-Radiopharma Ltd

2030 Érd, Szamos u. 10-12. Hungary

Other Sources of Information

This medication is found in the Member States of the European Economic Area with the following authorized names

Austria Medi-MIBI 500 Mikrogramm

Denmark Medi-MIBI

Italy Medi-MIBI 500microgrammi

Spain MIBI Radiopharmacy Laboratory 500 micrograms

This leaflet was last revised in August, 2015

The following information is intended only for healthcare professionals:

INSTRUCTIONS FOR THE PREPARATION OF RADIOPHARMACEUTICALS

The kit contents are not radioactive before preparation. However, after the addition of pertecnetate (99mTc) sodium injectable, European Pharmacopoeia, the obtained injectable solution must be placed in suitable shielding.

The administration of radiopharmaceuticals poses a risk to others due to external radiation or contamination from urine spills, vomiting, etc. Radiation protection precautions must be taken according to national regulations.

The preparation does not contain bacteriostatic preservatives.

Technetium (99mTc) sestamibi must be used within eight (8) hours following reconstitution. The vial is reconstituted with a maximum of 15 GBq of sterile, oxidant-free pertecnetate (99mTc) sodium.

As with any medication, it must not be used if, at any time during preparation, the integrity of the vial is not ensured.

Use only the eluate obtained from a molybdenum (99Mo)/technetium (99mTc) generator that has been eluted in the 24 hours prior. Use only the eluate from the generator obtained within 2 hours before reconstitution.

The kit labeling must be performed according to either method A or B. Instructions for the preparation of technetium (99mTc) sestamibiA. Boiling procedure:

The preparation of technetium (99mTc) sestamibi from the MIBI Radiopharmacy Laboratory 500 micrograms kit must be performed according to the following aseptic procedure:

1. Impermeable gloves must be used during the preparation procedure. Remove the cap from the MIBI Radiopharmacy Laboratory 500 micrograms kit vial and pass a cotton swab with alcohol over the top of the vial closure to disinfect the surface.
2. Place the vial in suitable shielding, labeled correctly with the date, preparation time, volume, and activity.
3. Using a syringe placed in a shield and sterilized, obtain, under aseptic conditions, pertecnetate (99mTc) sodium solution without additives, sterile and apyrogenic, in a maximum amount of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. Under aseptic conditions, add the pertecnetate sodium (99mTc) solution to the shielded vial. Without removing the needle, withdraw an equal volume of air to maintain atmospheric pressure inside the vial.
5. Shake vigorously, approximately 5 to 10 rapid up-and-down movements.
6. Remove the vial from the lead shield and place it in a vertical position in a boiling water bath, so that the vial is suspended above the bottom of the bath, and maintain boiling for 10 minutes. The bath must be shielded. The 10-minute time begins as soon as the water starts boiling again.
7. Note: The vial must be kept in a vertical position during boiling. Use a water bath in which the cap remains above the water level.
8. Remove the vial placed in the water bath shield and let it cool for fifteen minutes.
9. Before administration, visually inspect for the absence of particles and discoloration.
10. Extract all doses aseptically, using a shielded sterile syringe. Use the product within eight (8) hours following preparation.
11. The radiochemical purity must be checked before administration to the patient, according to the Radio-TLC method or the organic solvent extraction method detailed below.

Note: There is a possibility of breakage and significant contamination whenever vials containing radioactive material are heated.

Method “B” - Dry heat procedure

The preparation of technetium (99mTc) sestamibi from the MIBI Radiopharmacy Laboratory 500 micrograms kit must be performed according to the following aseptic procedure:

1. During the preparation procedure, impermeable gloves must be used. Remove the plastic disc from the MIBI Radiopharmacy Laboratory 500 micrograms kit vial and rub the top of the vial closure with a cleaning cloth to disinfect the surface.
2. Place the vial in suitable shielding, labeled correctly with the date, preparation time, volume, and activity.
3. Using a sterile syringe placed in a shield, obtain, under aseptic conditions, pertecnetate (99mTc) sodium solution without additives, sterile and apyrogenic, in a maximum amount of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. Under aseptic conditions, add the pertecnetate sodium (99mTc) solution to the shielded vial. Without removing the needle, withdraw an equal volume of air to maintain atmospheric pressure inside the vial.
5. Shake vigorously, using 5-10 rapid up-and-down movements.
6. Place the vial in the dry heaters. While gently pressing down, ensure there is a tight seal between the vial and the sample holder.
7. Press the start button to begin the heating program. After 10 minutes of boiling, place the vials in the vial shield and let them cool to room temperature.
8. Using leaded glasses, before administration, visually inspect for the absence of particles and discoloration.
9. Extract all doses aseptically, using a shielded sterile syringe. Use within eight hours following preparation.
10. Before administration to the patient, the radiochemical purity must be checked according to the Radio-TLC method and the organic solvent extraction method detailed below.
11. After reconstitution, store the MIBI Radiopharmacy Laboratory 500 micrograms labeled product at less than 25°C and protected from light.

Note: Do not use the product if the radiochemical purity is less than 94%.

After reconstitution, the packaging and all unused contents must be disposed of according to local requirements for radioactive materials.

Radio-TLC Method for the Quantification of Technetium (99mTc) Sestamibi

1. Materials 1.1 Baker-Flex-aluminum oxide plate, No. 1 B-F, pre-cut to 2.5 cm x 7.5 cm.
   1. Ethanol > 95%.
   2. Capintec, or equivalent instrument for radioactivity measurement in the range 0.01 MBq - 15 GBq. The resolution is 0.001 MBq.
   3. 1 ml syringe, with a 22 to 26 gauge needle.
   4. Small development tank with lid (a 100 ml Erlenmeyer flask covered with Parafilm is sufficient).

1. 2.1 Pour a sufficient amount of ethanol into the development tank (Erlenmeyer flask) to have a depth of 3 to 4 mm of solvent. Cover the tank (Erlenmeyer flask) with Parafilm and let it equilibrate for approximately 10 minutes.
2. 2.2 Apply a drop of ethanol, using a 1 ml syringe with a 22 to 26 gauge needle, to the aluminum oxide TLC plate, 1.5 cm from the bottom. Do not let the spot dry.
   1. Apply a drop of the kit solution to the ethanol spot. Let it dry. Do not heat!
   2. Let the solvent migrate a distance of 5.0 cm from the spot.
   3. Cut the strip 4 cm from the bottom and measure each part in the dose calibrator.
   4. Calculate the radiochemical purity in % as follows:

activity of the upper portion

% technetium (99mTc) sestamibi = -------------------------------------------------------- x100

activity of both portions

1. The % of technetium (99mTc) sestamibi must be ≥ 94%; otherwise, the preparation must be discarded.

II. Organic Solvent Extraction Method

Materials and Equipment

1. Sodium chloride solution
2. Chloroform
3. Mixer agitator
4. Capintec or equivalent instrument for radioactivity measurement in the range 0.01 MBq – 15 GBq. The resolution is 0.001 MBq.

Procedure

1. Add 0.1 ml of the labeled compound to a vial containing 3 ml of chloroform and 2.9 ml of saline solution.
2. Close the vial, mix in a mixer agitator for 1 min., and then wait until the phases separate (1-2 min).
3. Transfer the upper layer (saline) to another vial and measure the activities of both phases (vial of saline solution and vial of chloroform) separately in a dose calibrator. The (99mTc)-MIBI is lipophilic and is in the chloroform fraction, and the contaminants are in the saline layer.
4. Calculation

Calculate the percentage of 99mTc-MIBI Radiopharmacy Laboratory:

activity of the chloroform fraction

% of 99mTc-MIBI Radiopharmacy Laboratory lipophilic=------------------------------------------x100

total activity of both fractions

The percentage of radiochemical purity must not be less than 94% within eight hours