RENOSCAN MAG3 1 MG KIT FOR RADIOPHARMACEUTICAL PREPARATION - summary of medicine characteristics

Renoscan MAG3 1 mg kit for radiopharmaceutical preparation

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains Betiatide, 1 mg

It has to be reconstituted with sodium (99mTc) pertechnetate solution (not included in this kit) for the preparation of the diagnostic radiopharmace­utical: Technetium (99mTc) tiatide solution.

Excipient with known effect:

Each vial contains 4 mg sodium ions.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Kit for radiopharmaceutical preparation

The vial contains a sterile, white lyophilized powder.

4.1 Therapeutic indications

This medicinal product is for diagnostic use only.

After reconstitution and labelling with sodium (99mTc) pertechnetate solution, the diagnostic agent technetium (99mTc) tiatide may be used intravenously for the evaluation of nephrological and urological disorders in particular for the study of morphology, perfusion, and function of the kidney and characterisation of urinary outflow.

Posology

Adults and the elderly

37–185 MBq, depending on the pathology to be studied and the method to be used. Studies of renal blood flow or transport through the ureters generally require a larger dose than studies of intra-renal transport, whereas renography requires smaller activities than sequential scintigraphy.

Pediatric population

Although Renoscan MAG3 may be used in paediatric patients, formal studies have not been performed. Clinical experience indicates that for pediatric use the activity should be reduced. Because of the variable relationship between the size and body weight of patients it is sometimes more satisfactory to adjust activities to body surface area.

The activity to be administered in children and adolescents is determined according to the EANM dosage card (2016) using the following formula: The activity to be administered A[MBq] = Baseline activity (of 11.9 MBq ) x Multiple

The activities to be applied are listed in the following table:

In very young children, a minimum dose of 15 MBq is necessary in order to obtain images of sufficient quality.

The administration of a diuretic or an ACE inhibitor during the diagnostic procedure is sometimes used for differential diagnosis of nephrological and urological disorders. The scintigraphic investigation is usually performed immediately after administration

Method of administration

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

For intravenous use.

For multidose use.

The scintigraphic investigation is usually performed immediately after administration.

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

For patient preparation, see section 4.4.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Potential for hypersensitivity or anaphylactic reaction

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, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic information.

Pediatric population

The use in children has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group.

For information on the use in the pediatric population, see section 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.

Specific warnings

The agent is not suited for exact monitoring of effective renal plasma flow respectively blood flow in patients with seriously impaired renal function.

Small amounts of 99mTc-labelled impurities may be present and/or are formed during the labelling process. As some of these impurities are distributed to the liver and excreted via the gall bladder they may influence the late phase (after 30 minutes) of a dynamic renal study due to the overlap of kidney and liver in the region of interest.

Inadvertent or accidental subcutaneous administration of technetium (99mTc) tiatide should be avoided as perivascular inflammation has been described.

Excipients

This medicinal product contains less than 1 mmol sodium (23mg) per vial, that is to say essentially ‘sodium free’.

Depending on the time when you administer the injection, the content of the 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.

4.5 Interaction with other medicinal products and other forms of interaction Technetium (99mTc) tiatide has not been described to interfere with agents commonly prescribed to or given to patients requiring investigations with Technetium (99mTc) tiatide (e.g. antihypertensives and medicinal products used to treat or prevent organ transplant rejection).

However, the single administration of a diuretic or ACE inhibitor is sometimes used in the differential diagnosis of nephrological and urological disorders.

Administered contrast media may impair tubular renal excretion and thereby influence the technetium (99mTc) tiatide clearance.

4.6 Fertility, pregnancy and lactation

Women 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 doses 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 the foetus.

Breast-feeding

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 radiopharmace­utical, bearing in mind the secretion of activity in breast milk.

If the administration is considered necessary, breastfeeding should be interrupted for 4 hours and the expressed feeds discarded.

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)

1 Seen in a 15 days old child. Causal relationship not established.

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. For diagnostic nuclear medicine investigations the current evidence suggests that these adverse effects will occur with low frequency because of the low radiation doses incurred.

For most diagnostic investigations using nuclear medicine procedures the radiation dose delivered (Effective Dose Equivalent, EDE) is less than 20 mSv. Higher doses might be justified in some clinical circumstances

Reporting 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: www.mhra.gov.uk/yellowcard

4.9 Overdose

The risk of an excessive technetium (99mTc) tiatide dose is largely theoretical and most likely to be due to excessive radiation exposure. In such circumstances the radiation to the body (kidney, bladder and gall bladder) can be reduced by forced diuresis and frequent bladder voiding.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Diagnostic radiopharmace­uticals, renal system, technetium (99mTc) compounds.

ATC Code: V 09 CA 03

At the chemical doses envisaged technetium (99mTc) tiatide Injection has no known pharmacodynamic action.

Measuring the activity over the kidneys allows renal blood flow, intrarenal tubular transit times and excretion via the outflow tracts to be recorded separately for both kidneys.

5.2 Pharmacokinetic properties

Distribution

After intravenous injection technetium (99mTc) tiatide is rapidly cleared from the blood by the kidneys.

Organ uptake

Technetium (99mTc) tiatide has a relatively high binding to plasma proteins. In normal renal function 70 % of the administered dose has been excreted after 30 minutes and more than 95 % after 3 hours. These latter percentages are dependent on the pathology of the kidneys and the urogenital system.

Elimination

The mechanism of excretion is predominantly based on tubular secretion. Glomerular filtration accounts for 11 % of total clearance.

5.3 Preclinical safety data

Acute, subacute (8 days) and chronic (13 weeks) toxicity studies as well as mutagenicity studies were performed. At the studied dose levels, up to 1000 times the maximal human dose, no toxicological effects were observed. Similarly, mutagenic effects have not been observed.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium tartrate dihydrate

Stannous (II) chloride dihydrate

Hydrochloric acid for pH adjustment

6.2 Incompatibilities

Major incompatibilities are not known. However, in order not to compromise the stability of 99mTc-tiatide, preparations should not be administered together with other drugs.

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

6.3 Shelf life

18 months.

The expiry date is stated on the label of the immediate packaging vial and on the carton.

After radiolabelling: 8 hours. Store below 25 °C.

6.4 Special precautions for storage

Store in a refrigerator (2–8 °C).

Store in the outer carton in order to protect from light.

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

Storage should be in accordance with national regulations for radioactive materials.

6.5 Nature and contents of container

10 ml Type 1 Ph.Eur glass vial closed with a chlorobutyl rubber stopper Ph.Eur and sealed with an aluminium flip-cap.

Renoscan MAG3 is supplied as six or two vials in a carton.

Pack sizes

1 pack contains 6 vials.

Sample package: 2 vials.

6.6 Special precautions for disposal

General warning

This radiopharmaceutical 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 local competent official organisations.

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

The contents of the vial are to be labelled with Sodium Pertechnetate (99mTc) Injection. After reconstitution with the sodium (99mTc) pertechnetate solution, the diagnostic agent technetium (99mTc) tiatide is obtained upon boiling.

The administration of radiopharmace­uticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting etc. Radiation protection precautions in accordance with national regulations must therefore be taken. Any unused product or waste material should be disposed of in accordance with local requirements.

Only eluates obtained from a 99mTc-generator, which has been eluted within the preceding 24 hours, should be used. Dilution of the preparation should be done with saline.

After reconstitution and labelling the solution may be used for one or more administrations.

The vial does not contain a preservative agent.

Properties of the medicinal product after labelling:

Clear to slightly opalescent, colourless, aqueous solution.

pH 5.0–7.5

Osmolality: slightly hypertonic.

7 MARKETING AUTHORISATION HOLDER

Medi-Radiopharma Ltd.

2030 Érd, Szamos st. 10–12

Hungary

8 MARKETING AUTHORISATION NUMBER(S)

PL 27151/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

24/10/2017

10 DATE OF REVISION OF THE TEXT

01/07/2018

11 DOSIMETRY

The following radiation dosimetry is calculated according to the MIRD system. The data are given in ICRP publication 80 in 1998.

The following assumptions have been made in this model:

– In the normal case following intravenous administration of MAG3, the substance is rapidly distributed in the extracellular fluid and excreted entirely by the renal system according to the kidney-bladder model. Total body retention is described by a three-exponential function. The renal transit time is assumed to be 4 minutes as for Hippuran.

– When renal function is bilaterally impaired, it is assumed that the clearance rate of the substance is one tenth of that of the normal case, that the renal transit time is increased to 20 minutes, and that a fraction of 0.04 is taken up in the liver.

– As an example of acute unilateral renal blockage, it is assumed that a fraction of 0.5 of the administered radiopharmaceutical is taken up by one kidney and slowly released to the blood with a half-time of 5 days and subsequently excreted by the other kidney, which is assumed to function normally.

Normal renal function:

Absorbed doses 99mTc MAG3, 99mTc 6.02 h

Absorbed dose per unit activity administered (mGy/MBq)

For an administered activity of 185 MBq (Maximal dose) the effective dose is 1.3 mSv.

The absorbed dose in the target organ (kidney) is 0.63 mGy and the typical radiation dose to the critical organ (bladder wall) is 20 mGy.

Abnormal renal function:

Absorbed doses 99mTc MAG3,99mTc 6.02 h

Absorbed dose per unit activity administered (mGy/MBq)

For an administered activity of 185 MBq (Maximal dose) the effective dose is 1.1 mSv.

The absorbed dose in the target organ (kidney) is 2.6 mGy and the typical radiation dose to the critic organ (bladder wall) is 15 mGy.

Acute unilateral renal function:

Absorbed doses 99mTc MAG3,99mTc 6.02 h

Absorbed dose per unit activity administered (mGy/MBq)

GI-tract

For an administered activity of 185 MBq (Maximal dose) the effective dose is 1.85 mSv.

The absorbed dose in the target organ (kidney) is 37 mGy and the typical radiation dose to the critical organ (bladder wall) is 10 mGy.