MYOVIEW 230 micrograms kit for radiopharmaceutical preparation

This medicinal product is for diagnostic use only.

After reconstitution with Sodium Pertechnetate (^99mTc) Injection the product is indicated in adults for:

Myocardial Imaging

Myoview is a myocardial perfusion agent indicated as an adjunct in the diagnosis and localization of myocardial ischaemia and/or infarction.

In patients undergoing myocardial perfusion scintigraphy, ECG-gated SPECT can be used for assessment of left ventricular function (left ventricular ejection fraction and wall motion).

Breast Tumour Imaging

Myoview is indicated as an adjunct to the initial assessments (e.g. palpation, mammography, or alternative imaging modalities and/or cytology) in the characterisation of malignancy of suspected breast lesions where all these other recommended tests were inconclusive.

Posology

Paediatric population

Myoview is not recommended for use in children or adolescents as data are not available for these age groups.

Adults

Myocardial Imaging

Patients should be requested to fast overnight or to have only a light breakfast on the morning of the procedure.

For diagnosis and localization of myocardial ischaemia (using planar or SPECT techniques) and assessment of left ventricular function using ECG-gated SPECT, the usual procedure involves two intravenous injections of tetrofosmin (⁹⁹mTc), one given at peak stress and one given at rest. The order of the two administrations can be either rest first and stress second or stress first and rest second.

When rest and stress injections are administered on the same day, the activity administered for the second dose should result in a myocardial count rate at least three times greater than that of the residual activity from the first dose. The recommended activity range for the first dose is 250-400 MBq; the recommended activity range for the second dose given at least 1 hour later, is 600-800 MBq. For studies employing ECG-gated SPECT, use of activities at the higher end of these ranges is warranted.

When rest and stress injections are administered on different days, the recommended activity range for each dose of tetrofosmin (⁹⁹mTc) is 400-600 MBq. For studies on larger individuals (e.g. those with abdominal obesity or women with large breasts) and for those employing ECG-gated SPECT, use of activities at the higher end of this range is warranted.

The total activity administered for stress and rest myocardial imaging studies, whether performed on one or two days, should be restricted to 1200 MBq.

Based upon clinical trial data a minimum activity of 550 MBq has been shown to be adequate for ECG-gated SPECT. The activity administered for ECG-gated SPECT myocardial imaging should adhere to the guidelines specified in the previous paragraphs.

As an adjunct in the diagnosis and localization of myocardial infarction, one injection of tetrofosmin (⁹⁹mTc) (250-400 MBq) at rest is sufficient.

Planar or preferably SPECT imaging should begin no earlier than 15 minutes post-injection.

There is no evidence for significant changes in myocardial concentration or redistribution of tetrofosmin (⁹⁹mTc), therefore, images may be acquired up to at least four hours post injection.

For planar imaging the standard views (anterior, LAO 40° -45° , LAO 65° -70° and/or left lateral) should be acquired.

Breast Imaging

For the diagnosis and localization of suspected breast lesions, the recommended procedure involves a single intravenous injection of tetrofosmin (⁹⁹mTc) between 500– 750 MBq. The injection should preferably be given in a foot vein or a site other than the arm on the side of the suspected breast lesion. The patient does not need to fast before the injection.

Breast imaging optimally initiated 5 – 10 minutes post injection with the patient in the prone position with the breast(s) freely pendant. A special imaging couch designed for nuclear medicine breast imaging is recommended. A lateral image of the breast suspected of containing lesions should be obtained with the camera face as close to the breast as is practicable.

The patient should then be repositioned so that a lateral image of the pendant contralateral breast can be obtained. An anterior supine image may then be obtained with the patient's arms behind her head.

Method of administration

This medicinal product should be reconstituted before administration to the patient.

For instructions on reconstitution of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Must not be given during pregnancy (see section 4.6)

Potential for hypersensitivity or anaphylactic reactions

The possibility of hypersensitivity including anaphylactic/anaphylactoid reactions should always be considered. Advanced life support facilities should be readily available.

Paediatric population

Paediatric population, see section 4.2.

Individual benefit/risk justification

For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.

Renal impairment and hepatic impairment

Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.

Patient preparation

The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the examination in order to reduce radiation.

Breast lesions less than 1 cm in diameter may not all be detected with scintimammography as the sensitivity of Myoview for the detection of these lesions is 36% (n=5 of 14, 95% CI 13% to 65%) relative to histological diagnosis. A negative examination does not exclude breast cancer especially in such a small lesion.

Efficacy in the identification of axillary lesions has not been proven; consequently scintimammography is not indicated for staging breast cancer.

In myocardial scintigraphy investigations under stress conditions, the contraindications associated with the induction of stress should be considered.

Precautions with respect to environmental hazard see section 6.6

Specific warnings

This medicinal product contains 15 – 29 mg sodium per reconstituted vial, equivalent to 0.7 – 1.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

No formal studies on the interaction of Myoview with other drugs have been performed. However, no interactions were reported in clinical studies in which Myoview was administered to patients receiving co-medication. Drugs which influence myocardial function and/or blood flow, e.g. beta blockers, calcium antagonists or nitrates, can lead to false negative results in diagnosis of coronary artery disease. The results of imaging studies should always, therefore, be considered in the light of current medication.

Women of childbearing potential

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.

Pregnancy

Myoview is contraindicated in pregnancy (see section 4.3). Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Administration of 250 MBq tetrofosmin (^99mTc) at exercise, followed by 750 MBq at rest results in an absorbed dose to the uterus of 8.1 mGy. A radiation dose above 0.5 mGy (equivalent to the exposure from annual background radiation) would be regarded as a potential risk to the foetus.

Breast feeding

Before administering a radiopharmaceuticals to a mother who is breast feeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breast feeding and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. Tetrofosmin (⁹⁹mTc) is present in human milk in small amounts (<1% of maternal dose), If the administration is considered necessary, breastfeeding should be interrupted for 3 to 6 hours and the expressed feeds discarded.

Fertility

Animal reproductive toxicity studies have not been performed with this product.

No studies on the effects on the ability to drive and use machines have been performed

Summary of the safety profile

The listed frequencies are based on internal clinical documentation comprising approximately 3000 patients.

The frequencies of the undesirable effects are defined as follows:

Very Common (≥ 1/10), Common (≥ 1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100), Rare (≥ 1/10,000 to <1/1,000), Very Rare (<1/10,000) and not known (cannot be determined with the data available).

Adverse drug reactions following administration of tetrofosmin (^99mTc) are very rare (less than 1 in 10,000).

The following undesirable effects are recognised for Myoview:

Immune system disorders

Not known: Hypersensitivity reactions, including anaphylactoid or anaphylactic reactions and anaphylactic or anaphylactoid shock.

Nervous system disorders

Uncommon: Taste metallic

Rare: Disturbances of smell

Not known: Headache, dizziness

Eye disorders

Rare: Abnormal vision

Cardiac disorders

Not known: Tachycardia, chest pain

Vascular disorders

Uncommon: Flushing,

Not known: Hypotension

Respiratory, thoracic and mediastinal disorders

Not known: Dyspnoea, bronchospasm, throat tightness, cough

Gastrointestinal disorders

Uncommon: Vomiting

Rare: Abdominal pain, nausea, burning mouth

Skin and subcutaneous tissue disorder

Rare: Rash

Not known: Urticaria, pruritus, erythema, angioedema

General disorders and administration site conditions

Uncommon: Feeling of warmth

Not known: Local swelling, face oedema, fever

Investigations

Not known: White blood cell count increased.

Some reactions were delayed by several hours following administration of tetrofosmin (^99mTc). Isolated cases of serious reactions have been reported, including anaphylactic reaction (less than 1 in 100,000) and severe allergic reaction (single report).

Since the administered substance quantity is very low, the major risk is caused by the radiation. Exposure to ionising radiation is linked with cancer induction and a potential for developing hereditary defects..

As the effective dose is 8.5 mSv when the maximal recommended activity of 1200 MBq is administered these adverse reactions are expected to occur with a low probability.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the

Yellow Card Scheme, at Website: www.mhra.gov.uk/yellowcard.

In cases of overdosage of radioactivity frequent micturition and defaecation should be encouraged in order to minimize radiation dosage to the patient.

Pharmacotherapeutic group: diagnostic radiopharmaceuticals, cardiovascular system, technetium (^99mTc) tetrofosmin, ATC Code: V09GA02.

Pharmacological effects are not expected following intravenous administration of reconstituted Myoview at the recommended dosage. Studies in animals have shown that myocardial uptake of tetrofosmin (^99mTc) is linearly related to coronary blood flow, confirming the effectiveness of the complex as a myocardial perfusion imaging agent.

Based upon clinical experience with ECG-gated myocardial perfusion scintigraphy, this method can be used to monitor for changes (or stability) in left ventricular function over time. Reliability of such serial assessment is expected to be similar to that of other commonly used measurement techniques (e.g. ECG-gated blood-pool scintigraphy).

Limited data in animals show uptake of tetrofosmin (^99mTc) into breast tumour cells.

Organ uptake

Myocardial Uptake in the myocardium is rapid, reaching a maximum of about 1.2% of injected dose with sufficient retention to allow imaging of the myocardium by planar or SPECT techniques from 15 minutes up to 4 hours post-administration.

Elimination

Tetrofosmin (^99mTc) is rapidly cleared from the blood after intravenous injection; less than 5% of the administered activity remains in whole blood at 10 minutes post-injection. Background tissue clearance is rapid from lung and liver and activity is reduced in these organs following exercise, with enhanced sequestration in skeletal muscle. Approximately 66% of the injected activity is excreted within 48 hours post-injection, with approximately 40% excreted in the urine and 26% in the faeces.

Half-life

Sodium Pertechnetate (^99mTc) Injection Ph.Eur. is produced by a [99Mo/^99mTc] generator. Technetium (^99mTc) disintegrates with the emission of gamma radiation (energy 141 keV) and a half-life of 6.02 hours.

Renal/hepatic impairment

The pharmacokinetics in patients with renal or hepatic impairment has not been characterized

Acute toxicity studies employing Myoview at dosage levels of approximately 1050 times the maximum human single dose failed to reveal mortality or any significant signs of toxicity in rats or rabbits. In repeated dose studies some evidence of toxicity was observed in rabbits, but only at cumulative doses exceeding 10,000 times the maximum human single dose. In rats receiving these doses there was no significant evidence of toxicity. Studies on reproductive toxicity have not been conducted. Tetrofosmin showed no evidence of mutagenic potential in vitro or in vivo mutagenicity studies. Studies to assess the carcinogenic potential of Myoview have not been performed.

Stannous chloride dihydrate

Disodium sulphosalicylate

Sodium D-gluconate

Sodium hydrogen carbonate

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 12.

The shelf-life of the packaged product is 52 weeks.

Chemical and physical in-use stability of the reconstituted solution for injection has been demonstrated for 12 hours at 2° C-25° C.

Store the reconstituted product below 25° C. Do not freeze.

Store in a refrigerator (2° C -8° C). Store in the original package in order to protect from light.

For storage conditions of the reconstituted medicinal product, see section 6.3.

Storage should be in accordance with national regulations for radioactive materials

The product is supplied in a 10 ml clear glass vial sealed with a chlorobutyl rubber closure and flip off overseal.

Pack sizes: 2 or 5 vials.

Not all pack sizes may be marketed.

The reconstituted product is a clear colourless solution.

General warning

Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent official organisation.

Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Contents of the vial are intended only for use in the preparation of technetium (^99mTc) tetrofosmin injection and are not to be administered directly to the patient without first undergoing the preparative procedure.

For instructions on reconstitution of the medicinal product before administration, see section 12

If at any time in the preparation of this product the integrity of this vial is compromised it should not be used.

Administration procedures should be carried out in a way to minimise risk of contamination of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.

The content of the kit before reconstitution is not radioactive. However, after sodium pertechnetate (^99mTc), Ph. Eur. is added, adequate shielding of the final preparation must be maintained.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting etc. Radiation protection precautions in accordance with national regulations must therefore be taken

After use, all materials associated with the preparation and administration of radiopharmaceuticals, including any unused product and its container, should be decontaminated or treated as radioactive waste and disposed of in accordance with the conditions specified by the local competent authority. Contaminated material must be disposed of as radioactive waste via authorised route.