Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: A.C.O.M. - ADVANCED CENTER ONCOLOGY MACERATA S.R.L., Località Cavallino 39 A/B, 62010 Montecosaro (MC), Italy Tel.: 0039.0733.229739, Fax: 0039.0733.560352, E-mail: amministrazione@acompet.it
Cuprymina is a radiopharmaceutical precursor. It is not intended for direct use in patients. This medicinal product must be used only for the radiolabelling of carrier molecules, which have been specifically developed and authorised for radiolabelling with this radionuclide.
Cuprymina is only to be used by specialists experienced with in vitro radiolabelling
The quantity of Cuprymina required for radiolabelling and the quantity of Copper-64-labelled medicinal product that is subsequently administered will depend on the medicinal product radiolabelled and its intended use.
Refer to the Summary of Product Characteristics/package leaflet of the particular medicinal product to be radiolabelled.
Copper-64-labelled medicinal products should not be used in children and adolescents up to 18 years. For more information concerning paediatric use of Copper-64-labelled medicinal products refer to the Summary of Product Characteristics/package leaflet of the radiolabelled medicinal product.
Cuprymina is intended for in vitro radiolabelling of medicinal products, which are subsequently administered by the approved route.
Cuprymina should not be administered directly to the patient.
For instruction on preparation of the medicinal product, see section 12.
The radiation dose received by the various organs following intravenous administration of a Copper-64-labelled medicinal product is dependent on the specific molecule being radiolabelled. Information on radiation dosimetry of each different medicinal product following administration of the radiolabelled preparation is available in the Summary of Product Characteristics/package leaflet of the particular medicinal product to be radiolabelled. The dosimetry table below is presented in order to evaluate the contribution of non-conjugated Copper64 to the radiation dose following the administration of Copper-64-labelled medicinal product or resulting from an accidental intravenous injection of Cuprymina.
The dosimetry estimates were based on a mouse distribution study and the calculations were effected using OLINDA (Organ Level INternal Dose Assessment Code) (see Table 2). Time points for measurements were 2 minutes, 30 minutes, 1 hour, 4 hours, 6 hours, 12 hours, 24 hours, 2 days, 4 days, 6 days.
| Absorbed dose per unit activity administered (mGy/MBq) | |||||||
|---|---|---|---|---|---|---|---|
| Organ | Adult male (70 κιλά) | Adult female (60 κιλά) | 15 years | 10 years | 5 years | 1 year | Newborn |
| Adrenals | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Brain | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Breasts | 0.000596 | 0.000730 | 0.000732 | 0.00133 | 0.00204 | 0.00384 | 0.00776 |
| Gallbladder wall | 0.00192 | 0.00230 | 0.00219 | 0.00278 | 0.00453 | 0.00917 | 0.0158 |
| LLI wall | 0.0149 | 0.0160 | 0.0195 | 0.0340 | 0.0569 | 0.112 | 0.291 |
| Small intestine | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Stomach wall | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| ULI wall | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Heart wall | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Kidneys | 0.00885 | 0.00969 | 0.0107 | 0.0151 | 0.0224 | 0.0401 | 0.106 |
| Liver | 0.0211 | 0.0282 | 0.0283 | 0.0436 | 0.0649 | 0.126 | 0.294 |
| Lungs | 0.00178 | 0.00233 | 0.00245 | 0.00351 | 0.00526 | 0.00999 | 0.0240 |
| Muscle | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Ovaries | 0.00 | 0.00314 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Pancreas | 0.00267 | 0.00310 | 0.00365 | 0.00716 | 0.00955 | 0.0199 | 0.0637 |
| Red marrow | 0.00581 | 0.00565 | 0.00670 | 0.0118 | 0.0242 | 0.0586 | 0.198 |
| Osteogenic cells | 0.00202 | 0.00269 | 0.00263 | 0.00426 | 0.00718 | 0.0172 | 0.0549 |
| Skin | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Spleen | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Testes | 0.0463 | 0.00 | 0.114 | 0.907 | 1.05 | 1.41 | 2.02 |
| Thymus | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Thyroid | 0.000129 | 0.000156 | 0.000189 | 0.000292 | 0.000593 | 0.00113 | 0.00178 |
| Urinary bladder wall | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Uterus | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Effective dose (Sv/1 GBq administered) | |||||||
| Adult male | Adult female | 15 years | 10 years | 5 years | 1 year | Newborn | |
| 0.0962 | 0.0712 | 0.168 | 0.854 | 1.05 | 1.56 | 2.73 | |
For this medicinal product, the effective dose resulting from an intravenously injected activity of 925 MBq is 65.86 mSv for a 60-kg female adult and 88.99 mSv for a 70-kg male adult.
The presence of free copper (64Cu) chloride in the body after an inadvertent administration of Cuprymina will lead to increased hepatotoxicity.
Therefore, in case of an inadvertent administration of Cuprymina, the radiotoxicity for the patient must be reduced by immediate (i. e. within 1 hour) intravenous administration of preparations containing chelators like Ca-DTPA or Ca-EDTA in order to increase the elimination of the radionuclide from the body.
The following preparations must be available in medical institutions, which use Cuprymina for labelling of carrier molecules:
These chelating agents help elimination of copper radiotoxicity by an exchange between the calcium ion and the copper due to their capacity of forming water soluble complexes with the chelating ligands (DTPA, EDTA).
These complexes are rapidly eliminated by the kidneys.
1 g of the chelating agents should be administered by slow intravenous injection over 3–4 minutes or by infusion (1 g in 100-250 mL of glucose, or sodium chloride 9 mg/mL (0.9%) solution for injection). The chelating efficacy is greatest immediately or within one hour of exposure when the radionuclide is circulating in or available to tissue fluids and plasma. However, a post-exposure interval >1 hour does not preclude the administration and effective action of chelator, even if with reduced efficiency. Intravenous administration should not be protracted over more than 2 hours.
In any case the blood parameters of the patient have to be monitored and the appropriate actions immediately taken if there is evidence of damages.
The toxicity of the free Copper-64 due to in vivo release from the labelled biomolecule in the body during therapy could be reduced by post-administration of chelating agents.
48 hours from date and time of End of Synthesis (EOS).
Store in the original package that provides protection from radiation.
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
The radiopharmaceutical precursor solution is packaged in a colourless, type I glass 10 mL vial, closed with bromobutyl rubber stopper and aluminium overseal.
The volume of one vial ranges from 1 to 3 mL solution (corresponding to 925 to 2,770 MBq at calibration time).
The vials are packed into a tungsten or lead container for protective shielding.
Each pack contains 1 vial in a tungsten or lead container.
Cuprymina is not intended for direct use in patients.
Cuprymina is a sterile solution.
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 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.
For instruction on preparation of the medicinal product, see section 12.
If at any time in the preparation of this medicinal product the integrity of this container 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 surface dose rates and the accumulated dose depend on many factors. Measurements on the location and during work are critical and should be practiced for more precise and instructive determination of overall radiation dose to the staff. Healthcare personnel are advised to limit the time of close contact with patients injected with Copper-64-radiopharmaceuticals. The use of television monitor systems to monitor the patients is recommended. Given the long half-life of Copper-64 it is specially recommended to avoid internal contamination. For this reason it is mandatory to use protective high quality (latex/nitrile) gloves in any direct contact with the radiopharmaceutical (vial/syringe) and with the patient. For minimising radiation exposure with repeated exposition there is no recommendation except the strict observance of the above ones.
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.
Any unused medicinal product or waste material must be disposed of in accordance with local requirements.
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