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In the event of administration of a radiation overdose with technetium- (99mTc) mertiatide the absorbed dose to the patient should be reduced When an administration of radiopharmaceuticals to a woman of child- bearing potential is intended, it is important to determine whether or not where possible by increasing the elimination of the radionuclide from the IELMAG3 0.2 mg kit for radiopharmaceutical preparation she is pregnant. Any woman who has missed a period should be assu- body by frequent micturition or and frequent bladder voiding. It might be med to be pregnant until proven otherwise. If in doubt about her potential helpful to estimate the effective dose that was applied.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION pregnancy (if the woman has missed a period, if the period is very irre- This medicinal product should be reconstituted before administration to gular, etc.), alternative techniques not using ionising radiation (if there are The kit contains two different vials: (1) and (2).
any) should be offered to the patient.
Vial (1) contains 0.2 mg of the mertiatide (mercaptoacetyltriglycine).
The scintigraphic investigation is usually started immediately after admi- Vial (2) contains 2.5 mL phosphate buffer solution.
Radionuclide procedures carried out on a pregnant woman also involve Pharmacotherapeutic group: radiopharmaceuticals, ATC Code: For a full list of excipients, see section 6.1.
The radionuclide is not part of the kit. The kit contains all non radioactive For instructions on reconstitution and labelling of the medicinal product Only imperative investigations should therefore be carried out during No pharmaco-dynamic effect is known for technetium-(99mTc) mertiatide components required for the reconstitution of technetium-( preg nancy, when the likely benefit far exceeds the risk incurred by the Measuring the counts rate in the kidneys, over time, allows the evaluation of the renal perfusion, function and urinary outflow.
Hypersensitivity to the active substance, to any of the excipients listed Before administering a radioactive medicinal product to a mother who in section 6.1 or or to any of the components of the labelled radiophar- is breastfeeding consideration should be given to the possibility of de- Kit for radiopharmaceutical preparation.
laying the administration of radionuclide until the mother has ceased breast feeding, and to what is the most appropriate choice of radiophar- After intravenous injection technetium-(99mTc) mertiatide is rapidly cleared 4.4 Special warnings and precautions for use maceuticals, bearing in mind the secretion of activity into breast milk. If the administration is considered necessary, breast-feeding should be in- terrupted for 24 hours and the expressed feeds discarded. Technetium-(99mTc) mertiatide binds in a 78-90 % proportion to plasma Moreover, for radioprotection reasons, the mother is recommended to For each patient, the radiation exposure must be justifiable by the likely proteins. In normal renal function 70 % of the administered activity is ex- avoid close contact with the baby during the initial 24 hours following in- creted within 30 min. and more than 95 % within 3 hours. These values This medicinal product is for diagnostic use only. This is indicated for benefit. The activity administered should in every case be as low as rea - are dependent on the pathology of the kidneys and the urogenital sy- adults. For paediatric population see section 4.2.
sonably achievable to obtain the required diagnostic information.
After radiolabelling with sodium pertechnetate(99mTc) solution, the solution of technetium-(99mTc) mertiatide, is used for the evaluation of nephrological and urological disorders in particular for the study of function, morphology Careful consideration of the indication is required since the effective dose The mechanism of excretion is predominantly based on tubular secre- and perfusion of the kidneys and characterisation of urinary outflow. per MBq is higher than in adults (see section 11 “Dosimetry”).
4.7 Effects on ability to drive and use machines tion. Glomerular filtration accounts for 11 % of total clearance.
No studies on the effects on the ability to drive and use machines have 4.2 Posology and method of administration 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 It has been reported that no acute, subacute, subchronic or mutagenic examination in order to reduce radiation.
effects have been observed in preclinical studies. However, no detailed The following table presents how the frequencies are reflected in this information is available for these studies.
40 - 200 MBq, depending on the pathology to be studied and the me- Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, sto- Population aged less than 18 years rage, use, transfer and disposal are subject to the regulations and/or ap- propriate licences of the competent official organisation. Radiopharma- Although IELMAG3 0.2 mg kit for radiopharmaceutical preparation may ceuticals should be prepared by the user in a manner which satisfies be used in paediatric patients, formal studies have not been performed.
both radiation safety and pharmaceuticals quality requirements. Appro- Clinical experience indicates that, for paediatric use, the activity should priate aseptic precautions should be taken.
be reduced. Because of the variable relationship between the size and body weight of patients, it is sometimes more satisfactory to adjust ac- Not known (cannot be estimated from the available data) This medicinal product contains less than 1 mmol sodium (23 mg) per The use in children and adolescents has to be considered carefully, dose, i.e. essentially ‘sodium-free’.
Very rare mild anaphylactoid reactions have been reported (< 0.01 %), based upon clinical needs and assessing the risk/benefit ratio in this pa- If hypersensitivity or anaphylactic reactions occur, the administration of characterised by uriticarial rash, swelling of eyelids and coughing. tient group. The activities to be administered to children and to adole- the medicinal product must be discontinued immediately and intrave- Occasionally vasovagal reactions of a mild nature have been reported.
scents may be calculated according to the recommendations of the Eu- nous treatment initiated, if necessary. To enable immediate action in A cerebral convulsion in a sedated fifteen days old child has been re- ropean Association of Nuclear Medicine (EANM) paediatric dosage card; emergencies, the necessary medicinal products and equipment such as ported, but causative relation with the administration of the radiophar- the activity administered to children and to adolescents may be calcula- endotracheal tube and ventilator must be immediately available.
ted by multiplying a baseline activity (for calculation purposes) by the Precautions with respect to environmental hazard see section 6.6.
Exposure to ionisation radiation is linked with cancer induction and a po- weight-dependent multiples given in the table below. tential for development of hereditary defects. For diagnostic nuclear me- 4.5 Interaction with other medicinal products and other forms of dicine investigations current evidence suggests that these adverse ef- Not known. However, in order not to compromise the stability of tech- fects might only occur with low frequency because of the low radiation netium-(99mTc) mertiatide, preparations should not be administered to- Technetium-(99mTc) mertiatide is not known to interfere with agents com- monly prescribed to patients requiring the above mentioned investiga- For most diagnostic nuclear medical procedures, the radiation dose de- tions (e.g. antihypertensives or medicinal agents used to treat or prevent livered (E) is less than 20 mSv. A worst case calculation for the procedure in question gives values of 2 mSv for an adult and 0.76 mSv for a 1 year Under the influence of tubulary secreted hydrochlorothiazide a reduced old child after injection of 200 and 20 MBq respectively.
tubular secretion of the product has to be expected. This can in principle occur with other drugs that are secreted in the proximal tubule (e.g. non- Store the radiolabelled preparation at 2 – 8 °C.
The attending physician should request the patient to communicate each The previous administration of substances such as benzylpenicillin or io- dinated contrast media may also cause lower efficiency of the transport Reporting suspected adverse reactions after authorisation of the medi- Store in the original package in order to protect from light. It is reported that co-administration of metoclopramide reduces renal cinal product is important. It allows continued monitoring of the For storage conditions of the radiolabelled medicinal product, see sec- plasma flow. Therapeutic doses may result in reduced clearance values.
benefit/risk balance of the medicinal product. Healthcare professionals Dehydration and acidosis can also cause a prolonged elimination of the are asked to report any suspected adverse reactions via the national re- Storage of radiopharmaceuticals should be in accordance with national porting system listed in Appendix V. regulations on radioactive material.
case, that the renal transit time is increased to 20 minutes, and that As with any pharmaceutical product, if at any time in the preparation of a fraction of 0.04 is taken up in the liver. this product the integrity of this vial is compromised it should not be used.
Glass vial (10 mL) closed with a butyl rubber stopper and sealed with an aluminium crimpcap. IELMAG3 0.2 mg kit for radiopharmaceutical pre- • As an example of acute unilateral renal blockage, it is assumed that paration is supplied in packages containing five vials with powder (active a fraction of 0.5 of the administered radiopharmaceutical is taken up The radiopharmaceutical is prepared according to the following labelling substance: mertiatide) and five vials with 2.5 mL sterile phosphate buffer 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 assu- The radiolabelling procedure has to be carried out under aseptic condi- 6.6 Special precautions for disposal and other handling Place vial (1) into an adequate lead shielding. Swab the rubber septum with an appropriate disinfectant and let it dry. The content of the kit before reconstitution is not radioactive. However, Absorbed doses: Technetium (99mTc) mertiatide Remaining organs 0.00170 0.00210 0.00280 0.00340 0.00600 Inject 2 mL of sodium pertechnetate (99mTc) solution into vial (1) using a after [e.g. sodium pertechnetate (99mTc) Injection, Ph. Eur.] is added, ade- syringe. Then withdraw the same volume of nitrogen from the vial with quate shielding of the final preparation must be maintained.
Dose absorbed per activity administered [mGy/MBq] the same syringe for pressure compensation. The administration of radiopharmaceuticals creates risks for other per- Adults 15 year old 10 year old 5 year old 1 year old Shake the vial carefully in order to moisten. The complete content of the sons from external radiation or contamination from spill of urine, vomiting vial is for complete dissolution of any powder. etc. Radiation protection precautions in accordance with national regu- After 15 minutes reaction time transfer a volume of 2 mL buffer solution Absorbed doses: Technetium (99mTc) mertiatide from vial (2) into vial (1) using a new syringe. Then withdraw the same Radiopharmaceuticals should be received, used and administered only volume of nitrogen from the vial with the same syringe for pressure com- by authorised persons in designated clinical settings. Their receipt, sto- Dose absorbed per activity administered [mGy/MBq] rage, use, transfer and disposal are subject to the regulations and/or ap- Adults 15 year old 10 year old 5 year old 1 year old Shake carefully for good mixing. Determine the total radioactivity and propriate licences of the competent official organisation.
calculate the volume to be injected.
Radiopharmaceuticals should be prepared in a manner which satisfies If necessary, dilute with sterile isotonic saline up to a final total volume of both radiation safety and pharmaceutical quality requirements. Appro- priate aseptic precautions should be taken.
Contents of the vial are intended only for use in the preparation of tech- Properties of the product after radiolabelling: netium (99mTc) mertiatide and are not to be administered directly to the Appearance: Clear to slightly opalescent, colourless, aqueous solution.
patient without first undergoing the preparative procedure.
If at any time in the preparation of this product the integrity of this vial is Administration procedures should be carried out in a way to minimise risk of contamination of the medicinal product and irradiation of the ope- rators. Adequate shielding is mandatory.
The radiochemical purity of the labelled substance is examined by high For instructions on reconstitution and labelling of the medicinal product performance liquid chromatography (HPLC) using a suitable detector of before administration, see section 12.
radioactivity, on a 25 cm RP18 column, flow rate 1.0 mL/min. Mobile Any unused product or waste material should be disposed of in accor- phase A is a 93:7 mixture of phosphate solution (1.36 g KH PO , adjus - ted with 0.1 M NaOH to pH 6) and ethanol. Mobile phase B is a 1:9 mix- Use a gradient elution program with the following parameters: Chilcompton, Radstock BA3 4HP, United Kingdom Remaining organs 0.00130 0.00160 0.00210 0.00220 0.00360 The technetium-(99mTc) mertiatide peak appears at the end of the pas- The injection volume is 10 μl and the total count rate per channel must Bladder wall contributes up to 80% of the effective dose.
Effective dose if the bladder is emptied 1 or 0.5 hours after administration: Remaining organs 0.00210 0.00260 0.00360 0.00470 0.00800 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHO- Absorbed doses: Technetium (99mTc) mertiatide The effective dose resulting from the administration of a maximal recom- Dose absorbed per activity administered [mGy/MBq] mended activity of 200 MBq for an adult weighing 70 kg is about This method is based on cartridges, which are widely used as sample Adults 15 year old 10 year old 5 year old 1 year old For an administered activity of 200 MBq the typical radiation dose to the pre-treatment of aqueous solutions for chromatography. The cartridge target organ (kidney) is 0.68 mGy and the typical radiation dose to the (e.g. Sep-Pak Plus C 18, Waters) is washed with 10 mL absolute ethanol, critical organ bladder wall is 21.6 mGy.
followed by 10 mL 0.001 M hydrochloric acid. Remaining residues of the solutions are removed by 5 mL of air. 0.05 mL technetium(99mTc) mer- Technetium (99Tc) is produced by means of a (99Mo/99mTc) generator and tiatide solution is applied on the cartridge. Elute with 10 mL of 0.001 M decays with the emission of gamma radiation with a mean energy of 140 12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMA - hydrochloric acid and collect this first eluate (hydrophilic impurities). Elute keV and a half-life of 6.02 hours to technetium (99mTc) which, in view of the cartridge with ethanol/ 9 g/L sodium chloride solution in a ratio of its long half-life of 2.13 x 105 years can be regarded as quasi stable.
Radiolabelling should be done using an eluate with a radioactive con- 1:1. This second eluate contains technetium-(99mTc) mertiatide. The car- The data listed below are from ICRP publication 80 in 1998 and are cal- centration between 40 and 1250 MBq/mL. Only eluates obtained from tridge contains the lipophilic impurities. a generator, which has been eluted once in the preceding 24 hours, Measure the radioactivity of each portion. Sum up the radioactivity of The following assumptions have been made in this model: should be used. Dilution of the preparation should be done with saline.
the eluates and the cartridge as 100 % and calculate the respective per- The content of vial (1) is labelled with sodium pertechnetate (99mTc) solu- • In the normal case following intravenous administration of MAG3, the tion at room temperature. The radiolabelling reaction is stopped after 15 substance is rapidly distributed in the extracellular fluid and excreted Be aware to elute slowly (drop wise).
minutes by adding the buffer solution.
entirely by the renal system according to the kidney-bladder model.
Withdrawals should be performed under aseptic conditions. The vials Total body retention is described by a three-exponential function. The must not be opened before disinfecting the stopper, the solution should renal transit time is assumed to be 4 minutes as for Hippuran.
be withdrawn via the stopper using a single dose syringe fitted with suit - • When renal function is bilaterally impaired, it is assumed that the able protective shielding and a disposable sterile needle or using an au- Detailed information on this product is available on the website of the clear ance rate of the substance is one tenth of that of the normal European Medicines Agency http://www.ema.europa.eu

Source: http://www.rotop-pharmaka.de/fileadmin/user_upload/GFIs/MAG-3/SmPC-MAG3-UK-eng-01.pdf