PATIENT INFORMATION: Prospect

MIBI Radiopharmacy Laboratory 500 micrograms,

Radioactive Equipment for Radiochemical Preparation EFG

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

This medication is subject to additional monitoring, which will allow for the rapid identification of new safety information. You may collaborate by reporting any adverse effects you may experience. See the section 4 for information on how to report adverse effects.

Read the entire prospect before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your nuclear physician, who is responsible for supervising the procedure.
• In case you notice any adverse effect, report it to the nuclear physician. This includes any adverse effect not mentioned in this prospect. See section 4.

This medication is a diagnostic radiopharmaceutical, for use only.

MIBI Radiopharmacy Laboratory 500 microgramscontains a substance called tetrafluoroborato de [tetrakis(1-isocianida-2-metoxi-2-metilpropilo)cobre(I)], which is used to study heart function and blood flow (myocardial perfusion) through the performance of a cardiac image (scintigraphy), for example, to detect heart attacks (myocardial infarctions) 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 anomalies, along with other detection methods, when the results are confusing.MIBI Radiopharmacy Laboratory 500 microgramsmay also be used for the localization of hyperactive parathyroid glands (glands that secrete the hormone that controls blood calcium levels).

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

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

MIBI Radiopharmacy Laboratory 500 micrograms should not be used

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

Warnings and precautions

You should be especially careful withMIBI Radiopharmacy Laboratory 500 micrograms:

• if you are pregnant, or think you may be,
• if you are breastfeeding,
• 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 inform you if you need to take any special precautions after using this medication. Consult your nuclear medicine doctor if you have any doubts.

Before administration of MIBI Radiopharmacy Laboratory 500 micrograms:

• stay 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, in order to be able 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 medications and MIBI Radiopharmacy Laboratory 500 micrograms

There are a series of medications, foods, and beverages that may adversely affect the result of the planned test. Therefore, it is recommended that you consult your referring doctor about the medications you should suspend before the test, and which ones you should resume after the test. Also, inform your nuclear medicine doctor about any medication you are taking, have taken recently, or may have taken, as these may interfere with the interpretation of the images.

Please inform your nuclear medicine doctor about any medication you take that may affect heart function and/or blood flow.

Please consult your nuclear medicine doctor before taking any medication.

Pregnancy and lactation

You should inform your nuclear medicine doctor before administeringMIBI Radiopharmacy Laboratory 500 micrograms, if there is any possibility of pregnancy, if you have had a miscarriage, or if you are breastfeeding. In case of doubt, it is essential to consult the nuclear medicine doctor in charge of the procedure.

Your nuclear medicine doctor will only administer this medication during pregnancy if they consider that the benefits outweigh the risks.

If you are breastfeeding,

inform your nuclear medicine doctor, as they may request that you stop breastfeeding until the radioactivity in your body has dissipated, which occurs within 24 hours. The milk obtained during this period should be discarded. Consult them when you can resume breastfeeding.

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

Driving and operating machinery

The influence ofMIBI Radiopharmacy Laboratory 500 microgramson the ability to drive and operate machinery is considered negligible.

MIBI Radiopharmacy Laboratory 500 micrograms contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial, making it essentially 'sodium-free'. However, the administration of this medication 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.

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

The nuclear physician overseeing the procedure will decide on the amount ofMIBI Radiopharmacy Laboratory 500 microgramsto be used in your case. The goal will be to use the minimum amount necessary to obtain the desired information.

Normally, the recommended dose 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

The dose to be administered will be adapted to the child's weight in children and adolescents.

Administration of MIBI Radiopharmacy Laboratory 500 micrograms and procedure

MIBI Radiopharmacy Laboratory 500 microgramsis administered using a vein in the arm or leg (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 physician will inform you of any special precautions you should take after administration of this medication. Contact your nuclear physician if you have any questions.

You will be injected with the prepared solution in the vein 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 one after exercise (for example, during physical exercise or with pharmacological induction). The two injections will be spaced at least two hours apart, and no more than 2000 MBq will be administered in total (one-day protocol). A two-day protocol is also possible.

In isotopic mammography for breast lesions, 750 to 1100 MBq will be administered in the vein of the opposite arm or in the vein of the foot.

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

If the medication is to be used to acquire cardiac images, you will be asked not to eat anything 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 with fat, if possible, or to drink one or two glasses of milk, in order to reduce the radioactivity in your liver and improve the image.

Duration of the procedure

Your nuclear physician will inform you of 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.

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

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

Overdose is almost impossible since you will receive a controlled dose ofMIBI Radiopharmacy Laboratory 500 microgramsprecisely controlled by the nuclear physician overseeing the procedure. However, in the event of an overdose, you will receive the appropriate treatment. In particular, the nuclear physician in charge of the procedure may recommend that you drink abundantly to eliminateMIBI Radiopharmacy Laboratory 500 microgramsfrom your body.

If you have any questions about the use of this medication, consult your nuclear physician in charge of the procedure supervision.

Like all medications,MIBI Radiopharmacy Laboratory 500 microgramsmay cause side effects, although not everyone will experience them.

Rarely observed allergic reactions include difficulty breathing, extreme fatigue, nausea (usually within a period of 2 hours after administration), inflammation under the skin that may occur in areas such as the face and legs (angioedema) and obstruct airways, or cause a dangerous drop in blood pressure (hypotension) and decreased heart rate (bradycardia). Doctors are aware of this possibility and have emergency treatment available for use in these cases. Also, rare local skin reactions have been detected such as itching, urticaria, rash, inflammation, and redness. In case of experiencing any of the above reactions, contact your nuclear 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 minimum risk of cancer and genetic defects.

Information on side effects

In case of experiencing any side effect, report it to your nuclear doctor. This includes possible side effects not related to this prospectus. You may also report any side effect using the national reporting system included in Annex V. Reporting side effects can help provide more information about the safety of the medication.

Spanish System of Pharmacovigilance for Medicines for Human Use:www.notificaRAM.es

You will not be required to conserve this medication, as this responsibility falls under the specialist's in suitable locations. The conservation of radiopharmaceuticals will be carried out in accordance with national regulations on radioactive materials.

The following information is intended solely for specialists.

This medication should not be used after the expiration date included on the label.

Composition of MIBI Radiopharmacy Laboratory 500 micrograms

• The active principle is tetrafluoroborate of [tetrakis[(1-isocyanato-2-methoxy-2-methylpropyl)copper(I)].
• A vial contains 0.5 mg of tetrafluoroborate of [tetrakis[(1-isocyanato-2-methoxy-2-methylpropyl)copper(I)].
• The remaining ingredients are: Stannous chloride dihydrate, Cysteine hydrochloride monohydrate, Dodecahydrate sodium pyrophosphate, Sodium chloride, Glycine

Appearance of MIBI Radiopharmacy Laboratory 500 micrograms and packaging content

The product consists of a radiopharmaceutical preparation kit.

MIBI Radiopharmacy Laboratory 500 micrograms consists of tetrafluoroborate of [tetrakis[(1-isocyanato-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 sodium pertechnetate ( 99m Tc) is added to the vial, technetium ( 99m Tc) sestamibi is formed. This solution is ready for injection.

Package size:

6 vials

2x6 vials (Clinical packaging)

4x6 vials (Clinical packaging)

Holder of the Marketing Authorization and Manufacturing Authorization

Radiopharmacy Laboratory Ltd.

2040 Budaörs, Gyár u.2.

Hungary

Telephone: +36-23-886-950

Fax: +36-23-886-955

e-mail: [email protected]

Responsible for manufacturing:

Medi-Radiopharma Ltd

2030 Érd, Szamos u. 10-12. Hungary

Other sources of information

This medicinal product is available 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

This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

The contents of the kit are not radioactive before preparation. However, after the addition of sodium pertechnetate ( 99m Tc) injectable, European Pharmacopoeia, the resulting injectable solution must be placed in an appropriate shield.

The administration of radiopharmaceuticals involves a risk to others by external radiation or contamination by spills of urine, vomiting, etc. Appropriate precautions against radiation should be taken according to national regulations.

The prepared product does not contain bacteriostatic preservatives.

Technetium ( 99m Tc) sestamibi must be used within eight (8) hours after reconstitution. The vial is reconstituted with a maximum of 15 GBq of sodium pertechnetate ( 99m Tc) sterile and free of oxidants.

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

Only use the eluate obtained from a molybdenum ( 99 Mo)/technetium ( 99m Tc) generator that has been eluted within the past 24 hours. Only use the eluate from the generator obtained at most 2 hours before reconstitution.

The marking of the kit should be done according to method A or B. Instructions for the preparation of technetium (99mTc) sestamibi A. Boiling procedure:

1. Wear impermeable gloves during the preparation procedure. Remove the stopper from the vial of the MIBI Radiopharmacy Laboratory 500 micrograms kit and pass a cotton swab with alcohol over the top of the vial closure to disinfect the surface.
2. Place the vial in an appropriate shield, correctly labeled with the date, preparation time, volume, and activity.
3. Using a syringe placed in a protective sleeve and sterilized, obtain, in aseptic conditions, a solution of sodium pertechnetate ( 99m Tc) without additives, sterile and apyrogenic, in a maximum amount of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. In aseptic conditions, add the sodium pertechnetate ( 99m Tc) solution to the shielded vial. Without removing the needle, extract an equal volume of air to maintain atmospheric pressure inside the vial.
5. Agitate vigorously, approximately 5 to 10 rapid up-and-down movements.
6. Remove the vial from the lead shield and place it in a water bath in boiling, in such a way that the vial is suspended over 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. Nota: The vial must be kept in a vertical position during boiling. Use a water bath in which the stopper is above the water level.
8. Remove the vial from the water bath shield and let it cool for 15 minutes.
9. Before administration, visually inspect the absence of particles and discoloration.
10. Extract the material in aseptic conditions using a shielded syringe. Use the product within eight (8) hours after preparation.
11. Check the radiochemical purity before administration to the patient, according to the Radio TLC method or the organic solvent extraction method described below.

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

Método “B” - Procedure by dry heat

The preparation of technetium ( 99m Tc) sestamibi from the MIBI Radiopharmacy Laboratory 500 micrograms kit of radiopharmaceutical preparation reagents should be performed according to the following aseptic procedure:

1. During the preparation procedure, impermeable gloves should be worn. Remove the plastic disc 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, preparation time, volume, and activity.
3. Using a sterilized syringe placed in a protective sleeve, obtain, in aseptic conditions, a solution of sodium pertechnetate ( 99m Tc) without additives, sterile and apyrogenic, in a maximum amount of 15 GBq (405 mCi), in approximately 1 to 5 ml.
4. In aseptic conditions, add the sodium pertechnetate ( 99m Tc) solution to the shielded vial. Without removing the needle, extract an equal volume of air to maintain atmospheric pressure inside the vial.
5. Agitate vigorously, approximately 5 to 10 rapid up-and-down movements.
6. Place the vial in the dry heat calibrators. While pressing down gently, ensure that there is a tight seal between the vial and the sample support.
7. Press the start button to begin the heating program. After 10 minutes of heating, place the vials in the vial protector and let them cool to room temperature.
8. Using lead glasses, visually inspect the absence of particles and discoloration before administration.
9. Extract all doses aseptically using a sterile protected syringe. Use within eight hours after preparation.
10. Before administration to the patient, the radiochemical purity should be checked according to the Radio TLC method and the organic solvent extraction method described below.
11. After reconstitution, store MIBI Radiopharmacy Laboratory 500 micrograms marked at less than 25 o C and protected from light.

Nota: 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.

Método de Radio-TLC para la cuantificación del Tecnecio (99mTc) sestamibi

1. Materiales 1.1 Placa de Baker-Flex-óxido de aluminio, n.º 1 B-F, precortada en 2,5 cm x 7,5 cm.
   1. Etanol > 95 %.
   2. Capintec, or equivalent instrument for determining radioactivity in the range of 0.01 MBq to 15 GBq. The resolution value is 0.001 MBq.
   3. 1 ml syringe, with a 22 to 26 gauge needle.
   4. Small revelation container with a lid (a 100 ml precipitate vial covered with Parafilm is sufficient).

1. 2.1 Pour a sufficient amount of ethanol into the revelation container (precipitate vial) to have a depth of 3 to 4 mm of solvent. Cover the container (precipitate vial) with Parafilm and let it equilibrate for approximately 10 minutes.
2. 2.2 Apply a drop of ethanol, with the help of a 1 ml syringe with a 22 to 26 gauge needle, to the TLC aluminum oxide 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. Dry the spot. 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:

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