MEDI-EXAMETAZIME 500 MCG KIT FOR RADIOPHARMACEUTICAL PREPARATION - summary of medicine characteristics

Medi-Exametazime 500 microgram kit for radiopharmaceutical preparation

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 500 micrograms exametazime

The radionuclide is not part of the kit.

Excipients(s) with known effect:

Sodium 0.52 mg/vial

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Kit for radiopharmaceutical preparation White powder

4.1 Therapeutic indications

This medicinal product is for diagnostic use only. This is indicated for adults and elderly. For paediatric population see section 4.2.

After radiolabelling with sodium pertechnetate (99mTc) solution, the solution of technetium (99mTc) exametazime obtained is indicated for:

Neurology

Technetium (99mTc) exametazime is indicated for use with single photon emission tomography (SPECT).

In brain perfusion SPECT, the diagnostic target is detection of abnormalities of regional cerebral blood

flow. The following indications are sufficiently documented:

– Evaluation of patients with cerebrovascular disease (specifically acute stroke, chronic ischemia, and transient ischemic attack)

– Presurgical lateralization and localization of epileptogenic foci.

– Evaluation of patients with suspected dementia (specifically Alzheimer’s disease and frontotemporal dementia)

– Evaluation of patients with migraine

– Adjuvant technique in the diagnosis of brain death

Infectious or inflammatory diseases

In infectious or inflammatory diseases, the diagnostic target is tissue or structures in which labeled leukocytes are retained.

In infectious or inflammatory diseases, the following indications are sufficiently documented:

– Localisation of abnormal foci guiding the aetiologic diagnosis in case of fever of unknown origin

– Diagnosis of infection in case of suspected osteomyelitis (with or without implants) and suspected hip or knee prosthesis infection.

– Detection of the extension of inflammation in case of inflammatory bowel disease.

4.2 Posology and method of administrationPosology

Adults and elderly population

The suggested activity range for intravenous administration to an adult patient of average weight (70 kg) is for:

– Brain perfusion SPECT: 350–500 MBq

– For labelled leukocyte scintigraphy: 200 MBq

Renal/Hepatic impairment

In case of renal or hepatic impairment, exposure to ionising radiation can be increased. This must be taken into account when calculating the activity to be administered.

Paediatric population

The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. Safety and efficacy in paediatric population have not been fully established. Alternative techniques which do not involve ionising radiation should be especially considered.

The activities to be administered to children and adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) paediatric dosage card; the activity administered to children and to adolescents may be calculated by multiplying a baseline activity

(for calculation purposes) by the weight-dependent multiples given in the table below.

A[MBq]Administered = Baseline Activity x Multiple

The baseline activity is 51.8 MBq for brain perfusion SPECT, and the minimum activity is 100 MBq.

For labelled leukocyte scintigraphy, the baseline activity is 35 MBq and the minimum activity is 40 MBq.

Method of administration

– Brain perfusion SPECT: intravenous use. The radiopharmaceutical should be injected no sooner than 10 min but not later than 60 min after radioligand reconstitution.

– For labelled leukocyte scintigraphy: Leukocytes are labelled in vitro and subsequently labelled

leukocytes are for intravenous use.

Because of potential tissue damage extravasal injection of this radioactive product has to be strictly

avoided.

For multidose use.

Precautions to be taken before handling or administration of the medicinal product

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

reconstitution and control of the radiochemical purity of the medicinal product of the medicinal product

before administration, see section 12.

For patient preparation, see section 4.4.

Image acquisition

Brain perfusion SPECT

Imaging should be delayed 30–90 min after injection for best image quality.

Depending on the imagingdevice, typical scan time for triple head cameras is around 20–25 min (e.g. 120 projections, 40 projections per head, 20–25 s/projection); for dual head cameras it is closer to 30 min (e.g. 120 projections, 60 projections per head, 30 s/projection). Imaging should be completed within 4 hours post injection.

Labeled leukocyte scintigraphy

A large-field-of-view gamma camera with a low-energy high-resolution collimator is usually preferred.

Early imaging of the pelvis and abdomen is essential (bowel activity is seen in 20%-30% of children by 1 h and 2%-6% of adults by 3–4 h after injection). Images of the limbs should be acquired for 10 min/view at 4–8 h and at least 15 min/view at 16–24 h (particularly for osteomyelitis).

SPECT images of the chest, abdomen/pelvis,or spine may be helpful.

4.3 Contraindications

Hypersensitivity to the active substance(s), to any of the excipients listed in section 6.1 or to any of the components of the labelled radiopharmace­utical.

4.4 Special warnings and precautions for use

Potential for hypersensitivity or anaphylactic reactions

If hypersensitivity or anaphylactic reactions occurs, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

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 or Hepatic impairment

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

Paediatric population

For information on the use in paediatric population, see sections 4.2.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

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.

Brain perfusion SPECT

Patients should preferably avoid excessive stimulants (such as caffeine, cola, and energy drinks), alcohol, smoking, and any drugs known to affect cerebral blood flow prior to imaging.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Specific warnings

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium- free’.

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol. This should be

taken into account in patient on low sodium diet.

The preparation without reconstitution with sodium 99mTc-pertechnetate must not be administered to patients.

ReinjectedMedi -exametazime labelled leukocytes only

When preparing technetium (99mTc)-labelled leukocytes, it is essential that cells are washed free of sedimentation agents before they are re-injected into the patient as materials used in cell separation may cause hypersensitivity reactions.

Manipulation of human cells (labelling of leucocytes) carries the risk of potential transmission of infections (HBV, HIV, etc).

Precautions with respect to environmental hazard see section 6.6.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed and no drug interactions have been reported to date.

4.6 Fertility, pregnancy and lactationWomen of childbearing potential

When an administration of radiopharmace­uticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus

Breastfeeding

Before administering radiopharmace­uticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmace­uticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded. Breastfeeding can be restarted when the level in the milk will not result in a radiation dose to the child greater than 1mSv.

Close contact with infants should be restricted during this period.

No studies on fertility have been performed.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

The frequencies of 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 estimated from the available data)

Other disorder

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects.

As the effective dose is 4.7 mSv when the maximal recommended activity of 500 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 United Kingdom Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

In the event of administration of a radiation overdose with technetium (99mTc) exametazime, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by frequent micturition and defaecation. It might be helpful to estimate the effective dose that was applied.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: diagnostic radiopharmace­uticals, Technetium (99mTc) compounds, ATC code:

V09AA01 and V09HA02.

Pharmacodynamic effects

At the chemical concentrations used for diagnostic examinations, technetium (99mTc) exametazime solution

does not appear to have any pharmacodynamic activity.

5.2 Pharmacokinetic propertiesBrain perfusion SPECTDistribution

The technetium (99mTc) complex of the active ingredient is uncharged, lipophilic and of sufficiently low molecular weight to cross the blood-brain barrier.

It is rapidly cleared from the blood after intravenous injection.

Uptake in the brain reaches a maximum of 3.5–7.0% of the injected dose within one minute of injection.

Up to 15% of the cerebral activity washes out of the brain 2 minutes post injection after which there is little loss of activity for the following 24 hours except by physical decay of technetium (99mTc).

The activity not associated with the brain is widely distributed throughout the body particularly in muscle and soft tissue.

About 20% of the injected dose is removed by the liver immediately after injection and excreted through the hepatobiliary system.

About 40% of the injected dose is excreted through the kidneys and urine over the 48 hours after injection resulting in a reduction in general muscle and soft tissue background.

Technetium (99mTc) -labelled leukocytes distribute between the marginal pools of the liver (within 5 minutes) and spleen (within about 40 minutes), and the circulating pool, (the latter represents approximately 50% of the leukocyte pool). Approximately 37% of the cell associated technetium (99mTc) is recoverable from the circulating pool 40 minutes after injection. Technetium (99mTc) activity is slowly eluted from the cells and is excreted partly by the kidneys and partly via the liver into the gall bladder.

This results in increasing amounts of activity being seen in the intestines.

5.3 Preclinical safety data

Toxicological studies with mice have demonstrated that with a single IV injection of 2.5 mg/kg no deaths or pathological alteration were observed. Human safety factor 1750.

Toxicological studies with mice have demonstrated that with a single IV injection of 0.15 mg/kg no deaths or pathological alteration were observed. Human safety factor 105.

There is no additional preclinical safety data of relevance for the prescriber in recognising the safety profile of the product used for the authorised indications.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Stannous chloride dihydrate

Tetrasodium Pyrophosphate Decahydrate

Nitrogen

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 12.

6.3 Shelf life

12 months.

After radiolabelling: 60 minutes

Do not store above 25°C after radiolabelling.

Do not refrigerate or freeze

6.4 Special precautions for storage

Store at 2–8°C.

Do not freeze. Keep the vials in the outer carton in order to protect from light.

For storage conditions of the radiolabelled medicinal product, see section 6.3. Storage of radiopharmace­uticals should be in accordance with national regulation on radioactive materials.

6.5 Nature and contents of container

The product is supplied in 8 ml Type I Ph.Eur., clear, colourless, borosilicate glass vial sealed with a chlorobutyl rubber closure and oversealed with an aluminium overseal with a green flip off cap.

1 pack contains 3 multidose vials

1 pack contains 6 multidose vials

Sample package: 1 multidose vial

Bundle pack of 2 packs of 6 multidose vials

Bundle pack of 4 packs of 6 multidose vials

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

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

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) exametazime 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 sections 12.

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

The content of the kit before extemporary preparation is not radioactive. However, after sodium pertechnetate (99mTc) Injection, 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.

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. Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Radiopharmacy Laboratory Ltd

2040 Budaörs, Gyar st. 2 Hungary

(Budaörs Industrial and Technology Park

Gutenberg st. 125)

Phone: +36–23–886–950, 886–951

Fax: +36–23–886–955

e-mail: info@radiophar­macy-laboratory.eu

8 MARKETING AUTHORISATION NUMBER(S)

PL 40129/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/05/2017

10 DATE OF REVISION OF THE TEXT

10/05/2017

11 DOSIMETRY (IF APPLICABLE)