Consumer medicine information

CARDIOLITE

Technetium (99mTc) sestamibi

BRAND INFORMATION

Brand name

Cardiolite Powder for solution for injection

Active ingredient

Technetium (99mTc) sestamibi

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using CARDIOLITE.

What is in this leaflet

This leaflet answers some of the common questions about Cardiolite. It does not contain all of the available information about Cardiolite. It does not replace talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you or your child receiving Cardiolite against the benefits he or she expects it will have.

If you have any concerns about having this medicine, ask your doctor.

Keep this leaflet.

You may need to read it again.

What is Cardiolite

Cardiolite contains the active ingredient called Technetium Tc-99m Sestamibi and belongs to a group of medicines called radiopharmaceutical agents, which are all radioactive.

Cardiolite comes in a kit, containing ingredients that are mixed with a radioactive solution before being given to you as an injection.

What Cardiolite is used for

Cardiolite is used to show the blood flow inside your heart during exercise and rest.

Cardiolite can be used to show the presence and size of any breast cancer.

Your doctor may have prescribed Cardiolite for another purpose. Ask your doctor if you have any questions about why Cardiolite has been prescribed for you. If you have any concerns, you should discuss these with your doctor.

This medicine is only available with a doctor’s prescription.

Before you are given Cardiolite

Before you are given Cardiolite your doctor will explain to you the procedure you are about to undergo, and the radioactive medicine you will be given. You must discuss any concerns you have with your doctor.

Cardiolite is not recommended for patients less than 18 years of age. If your doctor believes it is necessary to give Cardiolite to a patient under 18, he or she will discuss the benefits and risks with you.

You must tell your doctor if you have allergies to:

  • any other medicines
  • any other substances such as foods, preservatives or dyes

Tell your doctor if you are or plan to become pregnant.

Like most medicines Cardiolite is not recommended for use during pregnancy. If there is a need to consider Cardiolite during your pregnancy, your doctor will discuss the benefits and risks of giving it to you.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Like most medicines Cardiolite is not recommended while you are breastfeeding. However if you are breastfeeding, formula feedings should be substituted for breastfeeding for 24 hours following the administration of Cardiolite. Breast milk produced within that time should be discarded.

Tell your doctor if you have any other medical conditions,

especially if you suffer from heart disease.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from pharmacy, supermarket or health food shop.

How Cardiolite is given

How much is given

Your doctor will decide how much you will be given. This depends on your condition and other factors, such as weight.

If you are being given Cardiolite for heart imaging you may be given two injections, one at rest and one with exercise. You may be asked to fast for 4 hours before the procedure, and may be given a light meal after the injection.

If you are being given Cardiolite for breast imaging you will be given one injection.

How it is given

Cardiolite is given as an injection into a vein. Cardiolite should only be given by a doctor or a nurse.

When you are given Cardiolite

Things you must do

You must drink about 2 litres of fluid and void urine frequently immediately after the procedure.

This will remove as much radioactivity as possible from your bladder.

Things you must not do

Do not take any other medicines until advised by your doctor.

Things to be careful of

Do not drive or operate machinery until you know how Cardiolite affects you.

Cardiolite may cause dizziness some people. Make sure you know how you react to Cardiolite before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy.

Side effects

Tell your doctor as soon as possible if you do not feel well after being given Cardiolite.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some side effects.

Tell your doctor if you experience any of the following and they worry you:

  • headache
  • nausea
  • things taste different
  • sleep disorders (such as nightmares, sleep terror or sleepwalking)
  • breast pain (women having breast imaging)
  • transient arthritis
  • flushing
  • oedema
  • injection site inflammation
  • dry mouth
  • fatigue

These side effects are usually mild.

Tell your doctor or a nurse immediately if you notice any of the following:

  • chest pain or a feeling of tightness, pressure or heaviness in the chest
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • changes in your heart rate
  • feeling faint
  • vomiting
  • abdominal pain
  • rash, itching or hives (itchy swellings on the skin)
  • allergic reaction - shortness of breath or difficulty breathing, slow heart rate, dizziness or light-headedness, feeling unusually tired or weak
  • fever

These are serious side effects for which you may need urgent medical treatment.

Do not be alarmed by this list of side effects.

You may not experience any of them.

Product description

What it looks like

Cardiolite is supplied in vials. An injection is prepared from the vial immediately before it is injected.

Ingredients

Active ingredient:
Technetium Tc-99m Sestamibi.

Ingredients before reconstitution:

  • tetrakis (2-methylisobutylisonitrile) copper (1) tetrafluoroborate,
  • stannous chloride,
  • sodium citrate,
  • cysteine hydrochloride, and
  • mannitol.

Sodium pertechnetate Tc-99 in water for injections.

Sponsor

Lantheus MI Australia Pty Ltd
Unit 8/24-26 Carrick Drive
Tullamarine
Victoria 3043

Registration Number

AUST R 49688

Date of Preparation

Updated: April 2012

Cardiolite(cmi)3.doc

BRAND INFORMATION

Brand name

Cardiolite Powder for solution for injection

Active ingredient

Technetium (99mTc) sestamibi

Schedule

Unscheduled

 

Name of the medicine

Technetium [99mTc] sestamibi.
Per vial: tetrakis (2-methoxy isobutyl isonitrile) copper (I) tetrafluoroborate 1.0 mg, tin (II) chloride 0.075 mg, sodium citrate 2.6 mg, cysteine hydrochloride 1.0 mg, mannitol 20 mg.

Description

The precise structure of the technetium complex is 99mTc[MIBI]6+ where MIBI is 2-methoxy isobutyl isonitrile. Prior to lyophilization the pH is 5.3 to 5.9. The contents of the vial are lyophilized and stored under nitrogen. This drug is administered by intravenous injection for diagnostic use after reconstitution with sterile, nonpyrogenic, oxidant free Sodium Pertechnetate 99mTc Injection. The product contains no preservatives.

Physical characteristics.

Technetium 99mTc decays by isomeric transition with a physical half-life of 6 hours. Photons associated with this transition which are useful for detection and imaging studies are listed below. (See Table 1.)

External radiation.

The specific gamma ray constant for 99mTc is 0.19 mGy per MBq-h at 1 cm. The first half value thickness of lead (Pb) for 99mTc is 0.2 mm. Attenuation by lead is given in Table 3.

Pharmacology

Clinical pharmacology.

99mTc sestamibi is a cationic 99mTc complex which has been found to accumulate in myocardial tissue in proportion to regional bloodflow, analogous to thallous [201Tl] chloride. However, unlike thallous [201Tl] chloride (which redistributes rapidly after the initial myocardial uptake), 99mTc sestamibi does not undergo appreciable redistribution after the initial myocardial uptake. Therefore, separate stress and resting studies are required to differentiate between transiently and persistently reduced myocardial uptake. Animal crossover experiments using thallous [201Tl] chloride and 99mTc sestamibi have confirmed that the myocardial distribution of 99mTc sestamibi correlates well with regional myocardial perfusion.
Scintigraphic images obtained in animals and man after the intravenous administration of 99mTc sestamibi have been comparable to those obtained with thallous [201Tl] chloride in patients with coronary insufficiency.
Studies using subcellular fractionation and electron micrographic analysis of heart cell aggregates have shown that 99mTc sestamibi cellular retention occurs specifically within the mitochondria as a result of electrostatic interactions. Secondary to increased metabolic requirements, cancer cells maintain more negative mitochondrial membrane potentials than normal cells. 99mTc sestamibi uptake in cancer cells is thus a multifunctional process dependent on delivery to the tumor and retention by electrostatic interaction.
The major pathway for clearance of 99mTc sestamibi is the hepatobiliary system. Twenty seven percent of the injected dose is excreted in the urine, and approximately thirty three percent of the injected dose is cleared through the feces in 48 hours.
Blood clearance studies indicate that the fast clearing component clears with a t1/2 of 3.0 minutes at rest,and 2.0 minutes under exercise conditions. At five minutes postrest injection, 9.1% of the injected dose remains in circulation; at 5 minutes post stress injection 6.5%. The myocardial t1/2 is 9.8 hours (95% CI: 6.3 - 13.3 hours) after rest injection and 9.7 hours (95% CI: 3.8-15.7 hours) after a stress injection. The t1/2 for the liver is 33.1 minutes (95% CI: 20.2-45.9 minutes) after a rest injection and 47.0 minutes (95% CI: 20.6-73.5 minutes) after a stress injection. The ideal imaging time (See Dosage and Administration) reflects the best compromise between heart count rate and surrounding organ uptake.
Myocardial uptake is 1.5% (95% CI: 1.2-1.8%) of the injected dose at exercise and 1.2% (95% CI: 0.8-1.6%) at rest. Animal studies have shown that uptake is coronary flow dependent and not blocked when the sodium pump mechanism is inhibited. However, hypoxia reduces the level of myocardial extraction.

Clinical Trials

Breast imaging.

Two multicenter trials enrolled 563 evaluable female subjects who were scheduled for excisional biopsy. In one trial the subjects had palpable breast abnormalities and in the other trial the subjects had mammographically detected, non-palpable breast abnormalities. The mean age of the populations was 49.4 ± 13.2 years and 54.3 ± 11.7 years, respectively. In both trials about 70% of the population was Caucasian and approximately 15% each African American and Hispanic.
Diagnostic evaluation included breast physical examination, mammography, scintigraphy and histopathology. For scintigraphy, lateral (10 minute) and anterior (10 minute) planar images were obtained beginning at 10 minutes after injection of 20-30 mCi of technetium [99mTc] sestamibi. Each scintigraphic image was read by the institutional physician who could have access to the patient's medical history and records of physical and mammographic findings and by three blinded readers who did not.
The diagnostic statistics for scintigraphic imaging and mammography when compared to core laboratory histopathology are displayed below for subjects with palpable abnormalities. (See Table 4.)
The diagnostic statistics for scintigraphic imaging when compared to core laboratory histopathology are displayed below for subjects with mammographically detected, non-palpable breast abnormalities. (See Table 5.)
Across the two trials, diagnostic accuracy was similar for patients of differing likelihood of malignancy as assessed by a mammographer and for differing breast densities.

Indications

Technetium [99mTc] sestamibi is indicated for use in conjunction with stress testing as an adjunct in the diagnosis of ischemic heart disease. In these patients additional information about ventricular function may be derived by using the first pass technique.
Technetium [99mTc] sestamibi is indicated as a second line diagnostic aid to assist in the evaluation of patients for whom mammography is inconclusive.

Contraindications

None known.

Warnings

Patients in whom cardiac disease is known or suspected should be studied under medical supervision. Care should be taken to assure continuous monitoring and treatment in accordance with safe, accepted clinical procedure. Infrequently, death has occurred 4 to 24 hours after 99mTc sestamibi use and is usually associated with exercise stress testing.

Precautions

General.

The contents of the vial are intended only for use in the preparation of technetium [99mTc] sestamibi and are not to be administered directly to the patient without first undergoing the preparative procedure.
The components of the kit are sterile and nonpyrogenic. It is essential to follow directions carefully and to adhere to strict aseptic procedures during preparation.
The technetium-99m labeling reactions depend on maintaining the stannous ion in the reduced state. Hence, Sodium Pertechnetate [99mTc] Injection containing oxidants should not be used.
Contents of the kit before preparation are not radioactive. However, after the Sodium Pertechnetate [99mTc] Injection is added, adequate shielding of the final preparation must be maintained.
Technetium [99mTc] sestamibi, as well as other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Also, care should be taken to minimize radiation exposure to the patient consistent with proper patient management.
The suitability of 99mTc-Pertechnetate derived from nonchromatographic generators has not been established for this product.
The product contains no antimicrobial preservative. It should be reconstituted aseptically and used within 6 hours of reconstitution.
To minimize the radiation dose to the bladder and other organs the patient should increase fluid intake (unless medically contraindicated) and void as frequently as possible after the injection for up to six hours.
Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides. The NH&MRC Code of Practice for the Disposal of Radioactive Wastes by the User (1985) should be observed.

Carcinogenesis, mutagenesis, impairment of fertility.

No long-term animal studies have been performed to evaluate carcinogenic potential or whether technetium [99mTc] sestamibi affects fertility in males or females. Several mutagenicity studies indicate that [Cu(MIBI)4]BF4 is not likely to induce mutagenic changes. However, in an in vitro study on human lymphocytes, [Cu(MIBI)4]BF4 resulted in chromosomal aberrations.

Use in pregnancy.

Animal reproduction and teratogenicity studies have not been conducted with technetium [99mTc] sestamibi. It is also not known whether technetium [99mTc] sestamibi can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. There have been no studies in pregnant women. Technetium [99mTc] sestamibi should not be given to a pregnant woman unless in the judgement of the treating clinician, its use is essential for the patient's welfare and the expected benefits outweigh the potential hazards.

Use in lactation.

99mTc-Pertechnetate is excreted in human milk during lactation. It is not known whether technetium [99mTc] sestamibi is excreted in human milk. Therefore, formula feedings should be substituted for breast feedings for at least 24 hours.

Paediatric use.

Safety and effectiveness in subjects below the age of 18 have not been established.

Adverse Effects

Adverse events were evaluated in 3741 adults who were evaluated in clinical studies. Of these patients, 3068 (77% men, 22% women, and 0.7% of the patients' genders were not recorded) were in cardiac clinical trials and 673 (100% women) in breast imaging trials. Cases of angina, chest pain, and death have occurred in cardiac imaging studies. Adverse events reported at a rate of 0.5% or greater after technetium [99mTc] sestamibi administration are shown in Table 6.
In the clinical studies for breast imaging, breast pain was reported in 12 (1.7%) of the patients. In 11 of these patients the pain appears to be associated with biopsy/ surgical procedures.
The following adverse reactions have been reported in ≤ 0.5% of patients: signs and symptoms consistent with seizure occurring shortly after administration of the agent; transient arthritis, angioedema, arrythmia, dizziness, syncope, vomiting, abdominal pain, pruritis, rash, urticaria, and severe hypersensitivity characterized by dyspnoea, hypotension, bradycardia, asthenia, and vomiting within two hours after a second injection of technetium [99mTc] sestamibi. A few cases of flushing, oedema, injection site inflammation, dry mouth, fever, and fatigue have also been attributed to administration of the agent.

Dosage and Administration

Cardiac imaging.

The suggested dose range for I.V. administration to be employed in the average patient (70 kg) is: 370-1110 MBq.
For diagnosis of ischemic heart disease, two injections (exercise and rest) are required in order to differentiate transiently from persistently reduced myocardial uptake. After the injection, exercise if used should be encouraged for an additional one to two minutes.
The patient dose should be measured by a suitable radioactivity calibration system immediately prior to patient administration. Radiochemical purity should be checked prior to patient administration.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration whenever solution and container permit. Adequate radiation shielding should be used for the inspection.
The product should be stored below 25°C and protected from light, before and after reconstitution.

Image acquisition.

If possible, the patient should fast for at least four hours prior to the study and should have a light meal after injection to assist upper intestinal clearance of the tracer.
The heart to background ratio will increase with time but the ideal imaging time, reflecting the best compromise between heart count rate and contrast, is approximately 1-2 hours after a rest injection and 0.25-2 hours after a stress injection. There is no evidence for significant changes in myocardial tracer concentration, or redistribution, therefore imaging up to six hours post injection is possible.
Planar or tomographic imaging (both of which can be performed with ECG gating) can be used for diagnosis of ischemic heart disease. For planar imaging, the standard three view (anterior, 45° LAO; 70° LAO, or LL) planar projections should be used. Static imaging time should be sufficient to acquire at least 1 million counts per view (approximately 5 minutes/view). For gated acquisition, imaging time should be 8-10 minutes/view.
For tomographic imaging, acquisition time/projection should be approximately 30 seconds.

Breast imaging.

The suggested dose range for I.V. administration to be employed in the average patient (70 kg) is 740-1110 MBq (20 - 30 mCi). The injection should be followed with a 10 mL saline flush.

Image acquisition.

It is generally suggested that images are obtained with a table overlay to separate breast tissue from the myocardium and liver, and to exclude potential activity that may be present in the opposite breast. For lateral images, position the patient prone with the isolateral arm comfortably above the head, shoulders flat against the table, head turned to the side and relaxed, with the breast imaged pendent through an overlay cutout. The breast should not be compressed on the overlay. For anterior images, position the patient supine with both arms behind the head. For either lateral or anterior images, shield the chest and abdominal organs, or remove them from the field of view.
For complete study, sets of images should be obtained five to ten minutes after the injection, and in the following sequence.
Beginning five to ten minutes after the injection of technetium [99mTc] sestamibi: ten minute lateral image of breast with abnormality; ten minute lateral image of contralateral breast; ten minute anterior image of both breasts.

Instructions for preparation of Technetium [99mTc] Sestamibi for Injection.

Preparation of the technetium [99mTc] sestamibi from the Kit for the Preparation of Technetium [99mTc] Sestamibi for Injection is done by the following aseptic procedure.
a. Prior to adding the Sodium Pertechnetate [99mTc] Injection to the vial, tear off a radiation symbol and attach it to the neck of the vial.
b. Waterproof gloves should be worn during the preparation procedure. Remove the plastic disc from the vial and swab the top of the vial closure with alcohol to sanitize the surface.
c. Place the vial in a suitable radiation shield with a fitted radiation cap.
d. With a sterile shielded syringe, aseptically obtain additive free, sterile, nonpyrogenic Sodium Pertechnetate [99mTc] Injection [925-5550 MBq] in approximately 1 to 3 mL.
e. Aseptically add the Sodium Pertechnetate [99mTc] Injection to the vial in the lead shield. Without withdrawing the needle, remove an equal volume of headspace to maintain atmospheric pressure within the vial.
f. Shake vigorously, about 5 to 10 upward-downward motions.
g. Remove the vial from the lead shield and place upright in an appropriately shielded and contained boiling water bath, such that the vial is suspended above the bottom of the bath, and boil for 10 minutes. Timing for 10 minutes is begun as soon as the water begins to boil again. Do not allow the boiling water to come in contact with the aluminum crimp.

Note.

The potential for cracking and significant contamination exists whenever vials containing radioactive material are heated.
h. Remove the vial from the water bath, place in the lead shield and allow to cool for fifteen minutes.
i. Using proper shielding, the vial contents should be visually inspected. Use only if the solution is clear and free of particulate matter and discoloration.
j. Assay the reaction vial using a suitable radioactivity calibration system. Record the technetium 99m concentration, total volume, assay time and date, expiration time and lot number on the vial shield label and affix the label to the shield.
k. Store the reaction vial containing the technetium [99mTc] sestamibi below 25°C until use; at such time the product should be aseptically withdrawn. Technetium [99mTc] sestamibi should be used within six hours of preparation. The vial contains no preservative.

Note.

It is important to adhere to the above product reconstitution instructions.
Product should be used within 6 hours after preparation.
The potential for cracking and significant contamination exists whenever vials containing radioactive material are heated.
Final product with radiochemical purity of at least 90% was used in the clinical trials that established safety and effectiveness. The radiochemical purity was determined by the following method.

Determination of radiochemical purity in technetium [99mTc] sestamibi.

1. Obtain a Baker-Flex aluminum oxide coated, plastic TLC plate, #1 B-F, precut to 2.5cm x 7.5cm.
2. Dry the plate or plates at 100°C for 1 hour and store in a desiccator. Remove predried plate from the desiccator just prior to use.
3. Apply 1 drop of 95% ethanol, 5% water using a 1mL syringe with a 22-26 gauge needle, 1.5 cm from the bottom of the plate. The spot should not be allowed to dry.
4. Add 2 drops of technetium [99mTc] sestamibi solution, side by side on top of the ethanol spot. Return the plate to a desiccator and allow the sample spot to dry (typically 15 minutes).
5. Develop the plate in the covered TLC tank in ethanol for a distance of 5 cm from the point of application.
6. Cut the TLC plate 4 cm from the bottom and measure the 99mTc activity in each piece by appropriate radiation detector.
7. Calculate the % 99mTc sestamibi as:
8. Do not use if the 99mTc sestamibi content is less than 90%.
Apply 2 adjacent drops of sample.

Radiation dosimetry.

The radiation doses to organs and tissues of an average patient (70 kg) per MBq of technetium [99mTc] sestamibi injected intravenously are shown in the Tables 7 and 8. The effective dose resulting from an administered amount of 925 MBq in the adult is 7.9 mSv at rest and 6.9 mSv at stress.

Overdosage

In the event of administration of a radiation overdose with technetium [99mTc] sestamibi the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by frequent micturation and defaecation.

Presentation

Kit for the preparation of technetium [99mTc] sestamibi for injection (sterile, nonpyrogenic, preservative free): 5's (kit contains 5 vials, 1 package insert, 6 vial shield labels, 6 radiation warning labels; AUST R 49688).

Storage

The product should be stored below 25°C and protected from light, before and after reconstitution.

Poison Schedule

Unscheduled.