MIBI Radiopharmacy Laboratory 500 micrograms radiopharmaceutical preparation kit EFG

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: Information for the Patient

MIBI Radiopharmacy Laboratory 500 micrograms,

Radiopharmaceutical kit for radiopharmaceutical preparation EFG

Tetrakis(1-isocyanido-2-methoxy-2-methylpropyl)copper(I) tetrafluoroborate

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

Read all of this leaflet before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your nuclear medicine physician, who is responsible for supervising the procedure.
• If you notice any adverse reaction, inform your nuclear medicine physician. This includes any adverse reaction not mentioned in this leaflet. See section 4.

Contents of this leaflet:

1. What MIBI Radiopharmacy Laboratory 500 micrograms is and what it is used for
2. What you need to know before using MIBI Radiopharmacy Laboratory 500 micrograms
3. How to use MIBI Radiopharmacy Laboratory 500 micrograms
4. Possible adverse reactions
5. How to store MIBI Radiopharmacy Laboratory 500 micrograms
6. Contents of the pack and other information

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

This medicine is a radiopharmaceutical for diagnostic use only.

MIBI Radiopharmacy Laboratory 500 micrograms contains a substance called [tetrakis(1-isocyanido-2-methoxy-2-methylpropyl)copper(I)] tetrafluoroborate, which is used to study heart function and blood flow (myocardial perfusion) by performing a cardiac image (scintigraphy), for example, to detect heart attacks (myocardial infarctions) or when a disease causes reduced blood supply to the entire heart muscle or to a part of it (ischemia). MIBI Radiopharmacy Laboratory 500 micrograms is also used for diagnosing cardiac abnormalities, together with other detection methods, when results are inconclusive. MIBI Radiopharmacy Laboratory 500 micrograms may also be used to locate hyperactive parathyroid glands (glands that secrete the hormone regulating calcium levels in the blood).

Once MIBI Radiopharmacy Laboratory 500 micrograms is 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 physician will then take an image (scintigraphy) of the organ in question, providing valuable information about the organ's structure and function, or the location of a tumor, for example.

The use of MIBI Radiopharmacy Laboratory 500 micrograms involves exposure to small amounts of radioactivity. Your physician and the nuclear medicine physician have determined that the clinical benefit you may obtain from this radiopharmaceutical procedure outweighs the risk associated with radiation exposure.

2. What you should know before using MIBI Radiopharmacy Laboratory 500 micrograms

MIBI Radiopharmacy Laboratory 500 micrograms must not be used

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

Warnings and precautions

Take special care with MIBI Radiopharmacy Laboratory 500 micrograms:

• if you are pregnant, or think you might be pregnant,
• if you are breastfeeding,
• if you have kidney or liver disease.

You must inform your nuclear medicine physician in any of the above cases. Your nuclear medicine physician will let you know whether you need to take any special precautions after receiving this medicine. Please consult your nuclear medicine physician about any questions you may have.

Before administration of MIBI Radiopharmacy Laboratory 500 micrograms:

• remain fasting 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, so that you can urinate frequently during the first few hours after the study.

Children and adolescents

Please consult your nuclear medicine physician if you are under 18 years of age.

Use of other medicines and MIBI Radiopharmacy Laboratory 500 micrograms

There are several drugs, foods, and beverages that may adversely affect the outcome of the planned test. Therefore, it is recommended that you consult your referring physician about which medications should be discontinued before the test, and which ones should be resumed afterward. Also inform your nuclear medicine physician about any medication you are currently taking, have recently taken, or might have taken, as these may interfere with the interpretation of the images.

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

Please consult your nuclear medicine physician before taking any medication.

Pregnancy and breastfeeding

You must inform your nuclear medicine physician before administration of MIBI Radiopharmacy Laboratory 500 micrograms if there is any possibility you may be pregnant, if you have missed a period, or if you are breastfeeding. If in doubt, it is important to consult the nuclear medicine physician in charge of supervising the procedure.

If you are pregnant,

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

If you are breastfeeding,

inform your nuclear medicine physician that you are breastfeeding, as they may instruct you to interrupt breastfeeding until radioactivity is no longer present in your body, which occurs within 24 hours. Breast milk collected during this period should be discarded. Consult your physician about when you can resume breastfeeding.

If you are pregnant, breastfeeding, suspect you may be pregnant, or plan to become pregnant, consult your nuclear medicine physician before using this medicine.

Driving and using machines

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

MIBI Radiopharmacy Laboratory 500 micrograms contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore considered essentially 'sodium-free'.

The administration of this medicine 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 physician.

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 micrograms will be used only in specially controlled areas. This product will be handled and administered exclusively by trained and qualified personnel competent in its safe use. Such individuals will take particular care in the safe use of this product and will keep you informed about their actions.

The nuclear medicine physician supervising the procedure will determine the amount of MIBI Radiopharmacy Laboratory 500 micrograms to be used in your case. The smallest possible amount required to obtain the desired information will be used.

Normally, the recommended dose for an adult varies depending on the test being performed and ranges between 200 and 2000 MBq (Megabecquerels, the unit used to express radioactivity).

Use in children and adolescents

In children and adolescents, the administered dose will be adjusted according to the child's body weight.

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

MIBI Radiopharmacy Laboratory 500 micrograms is administered via a vein in the arm or foot (intravenous administration). One or two injections will be sufficient to perform the test required by your doctor.

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

The nuclear medicine physician will inform you about any special precautions you should take after receiving this medication. Contact your nuclear medicine physician if you have any questions.

The solution will be injected intravenously before image acquisition. Imaging will take place 5 to 10 minutes after injection, or even up to 6 hours later, depending on the type of test.

For cardiac studies, two injections may be necessary: one at rest and another after stress (e.g., during physical exercise or pharmacological stimulation). 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.

For breast lesion imaging, an injection of 750 to 1100 MBq will be administered into a vein in the arm opposite to the affected breast or into a vein in the foot.

For localization of hyperactive parathyroid glands, the administered activity will range between 185 and 1100 MBq, depending on the method used.

If the medication is to be used for cardiac imaging, you will be asked not to eat for at least 4 hours before the test. After the injection, but before imaging (scintigraphy), you will be asked to consume a low-fat meal, if possible, or to drink one or two glasses of milk, in order to reduce radioactivity in your liver and improve image quality.

Duration of the procedure

Your nuclear medicine physician will inform you about the expected duration of the procedure.

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

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

The nuclear medicine physician will inform you of any special precautions you should take after receiving this medication. Consult your nuclear medicine physician if you have any questions.

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

Overdose is almost impossible, as you will receive a dose of MIBI Radiopharmacy Laboratory 500 micrograms precisely controlled by the nuclear medicine physician supervising the procedure. However, in the event of an overdose, appropriate treatment will be provided. In particular, the nuclear medicine physician in charge of the procedure may advise you to drink plenty of fluids to help eliminate MIBI Radiopharmacy Laboratory 500 micrograms from your body.

If you have any doubts about the use of this medication, consult the nuclear medicine physician supervising the procedure.

4. Possible adverse effects

Like all medicines, MIBI Radiopharmacy Laboratory 500 micrograms may cause adverse effects, although not everyone experiences them.

Allergic reactions have rarely been observed, such as difficulty breathing, extreme fatigue, nausea (usually within 2 hours after administration), swelling under the skin that may occur in areas such as the face and legs (angioedema) and may obstruct the airways, or lead to a dangerous drop in blood pressure (hypotension) and decreased heart rate (bradycardia). Physicians are aware of this possibility and have emergency treatments available for use in such cases. Rare local skin reactions have also been reported, including itching, urticaria, rash, swelling, and redness. If you experience any of the above reactions, contact your nuclear medicine physician immediately.

Other possible adverse 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 hereditary defects.

Information on adverse reactions

If you experience any adverse reaction, inform your nuclear medicine physician. This includes possible adverse reactions not listed in this leaflet. You may also report any adverse reaction using the national reporting system included in Annex V. By reporting adverse reactions, you can help provide more information on the safety of the medicine.

Spanish System for Pharmacovigilance of Human Medicinal Products: www.notificaRAM.es

5. Storage of MIBI Radiopharmacy Laboratory 500 micrograms

You will not be responsible for storing this medicinal product, as storage is the responsibility of specialists in appropriate locations. Radioactive pharmaceuticals must be stored in accordance with national regulations concerning radioactive materials.

The following information is intended for specialists only.

This medicine must not be used after the expiry date stated on the label.

6. Package contents and other information

Composition of MIBI Radiopharmacy Laboratory 500 micrograms

• The active substance is tetrafluoroborate [tetrakis[(1-isocyanido-2-methoxy-2-methylpropyl)copper(I)].
• One vial contains 0.5 mg of tetrafluoroborate [tetrakis[(1-isocyanido-2-methoxy-2-methylpropyl)copper(I)].
• The other ingredients are: stannous chloride dihydrate, monohydrate cistine hydrochloride, tetrasodium pyrophosphate decahydrate, sodium chloride, glycine.

Appearance of MIBI Radiopharmacy Laboratory 500 micrograms and contents of the container

The product consists of a kit for radiopharmaceutical preparation.

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

Container sizes:

6 vials

2x6 vials (Clinical pack)

4x6 vials (Clinical pack)

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: [email protected]

Manufacturer:

Medi-Radiopharma Ltd

2030 Érd, Szamos u. 10-12. Hungary

Other sources of information

This medicine is marketed in the European Economic Area member states under the following authorized names:

Austria: Medi-MIBI 500 Microgram

Denmark: Medi-MIBI

Italy: Medi-MIBI 500 microgrammi

Spain: MIBI Radiopharmacy Laboratory 500 microgramos

This leaflet was last reviewed in August 2015

The following information is intended for healthcare professionals only:

INSTRUCTIONS FOR THE PREPARATION OF RADIOACTIVE PHARMACEUTICALS

The contents of the kit are non-radioactive prior to preparation. However, after the addition of injectable sodium pertechnetate (99mTc), European Pharmacopoeia, the resulting injectable solution must be placed in appropriate shielding.

Administration of radiopharmaceuticals poses a risk to others due to external radiation or contamination from spills of urine, vomit, etc. Radiation protection precautions must be taken in accordance with national regulations.

The preparation does not contain bacteriostatic preservatives.

Technetium (99mTc) sestamibi must be used within eight (8) hours after reconstitution. The vial is reconstituted with up to 15 GBq of sterile, oxidant-free sodium pertechnetate (99mTc).

As with any medicinal product, it must not be used if, at any point during preparation, the integrity of the vial is compromised.

Use only eluate obtained from a molybdenum (99Mo)/technetium (99mTc) generator eluted within the previous 24 hours. Use only eluate obtained no more than 2 hours before reconstitution.

Labeling of the kit must be performed according to either method A or B. Instructions for preparation of technetium (99mTc) sestamibi

Method A – Boiling procedure:

Preparation of technetium (99mTc) sestamibi from the MIBI Radiopharmacy Laboratory 500 micrograms kit must be carried out according to the following aseptic procedure:

1. Wear impermeable gloves during the preparation procedure. Remove the cap from the vial of the MIBI Radiopharmacy Laboratory 500 micrograms kit and disinfect the surface of the vial closure with an alcohol-impregnated swab.
2. Place the vial in an appropriate shield, correctly labeled with the date, time of preparation, volume, and activity.
3. Using a syringe placed in a syringe shield, aseptically withdraw sterile, pyrogen-free sodium pertechnetate (99mTc) solution without additives, up to a maximum of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. Aseptically add the sodium pertechnetate (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 with approximately 5 to 10 rapid up-and-down movements.
6. Remove the vial from the lead shield and place it vertically in a shielded boiling water bath, ensuring the vial is suspended above the bottom of the bath. Boil for 10 minutes. The bath must be shielded. The 10-minute period starts as soon as the water begins to boil again.
7. Note: The vial must remain in a vertical position during boiling. Use a water bath in which the cap remains above the water level.
8. Remove the shielded vial from the water bath and allow it to cool for fifteen minutes.
9. Before administration, visually inspect for the absence of particles and discoloration.
10. Aseptically withdraw the material using a shielded syringe. Use the product within eight (8) hours after preparation.
11. Radiochemical purity must be checked before administration to the patient, using either the Radio TLC method or the organic solvent extraction method described below.

Note: There is a risk of vial breakage and significant contamination when heating vials containing radioactive material.

Method B – Dry heat procedure

Preparation of technetium (99mTc) sestamibi from the MIBI Radiopharmacy Laboratory 500 micrograms kit for radiopharmaceutical labeling must be carried out according to the following aseptic procedure:

1. Impermeable gloves must be worn during the preparation. Remove the plastic disk from the vial of the MIBI Radiopharmacy Laboratory 500 micrograms kit and wipe the top of the vial closure with a cleaning cloth to disinfect the surface.
2. Place the vial in an appropriate shield, correctly labeled with the date, time of preparation, volume, and activity.
3. Using a sterile syringe placed in a syringe shield, aseptically withdraw sterile, pyrogen-free sodium pertechnetate (99mTc) solution without additives, up to a maximum of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. Aseptically add the sodium pertechnetate (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 with 5–10 rapid up-and-down movements.
6. Place the vial into the dry heaters. While gently pressing down, ensure a tight seal between the vial and the sample holder.
7. Press the start button to initiate the heating program. After 10 minutes of boiling, place the vials into the vial shield and allow them to cool to room temperature.
8. Using leaded glasses, visually inspect before administration for the absence of particles and discoloration.
9. Aseptically withdraw all doses using a sterile shielded syringe. Use within eight hours after preparation.
10. Before administration to the patient, radiochemical purity must be checked using the Radio TLC method and the organic solvent extraction method described below.
11. After reconstitution, store labeled MIBI Radiopharmacy Laboratory 500 micrograms at less than 25°C and protected from light.

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

After reconstitution, the container and any unused contents must be disposed of in accordance with local requirements for radioactive materials.

Radio-TLC method for 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.
   1.2 Ethanol > 95%.
   1.3 Capintec, or equivalent instrument for measuring radioactivity in the range of 0.01 MBq to 15 GBq. Resolution value: 0.001 MBq.
   1.4 1 ml syringe with 22–26 gauge needle.
   1.5 Small developing tank with lid (a 100 ml beaker covered with Parafilm® is sufficient).

2.1 Pour a sufficient amount of ethanol into the developing tank (beaker) to achieve a solvent depth of 3–4 mm. Cover the tank (beaker) with Parafilm® and allow it to equilibrate for approximately 10 minutes.
2.2 Using a 1 ml syringe with a 22–26 gauge needle, apply a drop of ethanol onto the aluminum oxide TLC plate, 1.5 cm from the bottom. Do not allow the spot to dry.
2.3 Apply a drop of the kit solution onto the ethanol spot. Allow the spot to dry. Do not heat!
2.4 Allow the solvent to migrate a distance of 5.0 cm from the spot.
2.5 Cut the strip 4 cm from the bottom and measure each portion in a dose calibrator.
2.6 Calculate radiochemical purity in % as follows:

% technetium (99mTc) sestamibi = (activity of upper portion / total activity of both portions) × 100

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-shaker
4. Capintec or equivalent instrument for measuring radioactivity in the range 0.01 MBq – 15 GBq. Resolution: 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 on a mixer-shaker for 1 minute, then wait 1–2 minutes for phase separation.

3. Transfer the upper layer (saline) to another vial and separately measure the activities of both phases (saline vial and chloroform vial) using a dose calibrator. The lipophilic (99mTc)-MIBI complex is in the chloroform fraction, while contaminants remain in the saline layer.

4. Calculation

   Calculate the percentage of 99mTc-MIBI Radiopharmacy Laboratory:

   % of lipophilic 99mTc-MIBI Radiopharmacy Laboratory = (activity of chloroform fraction / total activity of both fractions) × 100

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