Cuprymina

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Cuprymina 925 MBq/mL radiopharmaceutical precursor, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL of solution contains 925 MBq of copper (64Cu) chloride at calibration time (01h00 a.m. 
Central European Time [CET]), corresponding to at least 0.25 micrograms of Copper-64. The 
calibration time is set between the end of the synthesis time and the expiry time. 
 
Each vial contains an activity ranging from 925 MBq to 2,770 MBq (at calibration time) which 
corresponds to an amount of 0.25 to 0.75 micrograms of Copper-64. The volume varies from 1 to 3 mL. 
 
The minimal specific activity is 3,700 MBq Copper-64/micrograms of Copper at the expiry date and 
time. 
Copper-64 has a half-life of 12.7 hours. 
Copper-64 decays by an emission of β+ (17.6 %) with a maximum energy of 0.66 MeV, an emission of 
β- (38.5 %) with a maximum energy of 0.58 MeV and electronic capture (43.9 %). 
Copper-64 decays in stable Nickel 64Ni (61 %) by an emission of β+ (18 %) or by an electronic capture 
(43 %). Copper-64 decays also in stable Zinc (64Zn) by emission of β- (39 %). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Radiopharmaceutical precursor, solution.  
Clear, colourless solution, free of particulate matter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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. 
 
4.2 Posology and method of administration 
 
Cuprymina is only to be used by specialists experienced with in vitro radiolabelling  
 
Posology 
 
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.  
 
Paediatric population 
 
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. 
 



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Method of administration 
 
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. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Established or suspected pregnancy or when pregnancy has not been excluded (see section 4.6). 
 
For information on contraindications to particular Copper-64-labelled medicinal products prepared by 
radiolabelling with Cuprymina refer to the Summary of Product Characteristics/package leaflet of each 
particular medicinal product to be radiolabelled. 
 
4.4 Special warnings and precautions for use 
 
Individual benefit/risk justification 
 
Cuprymina is not to be administered directly to the patient but must be used for the radiolabelling of 
carrier molecules, such as monoclonal antibodies, peptides or other substrates. 
 
General warnings 
 
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 by the user in a manner which satisfies both radiation safety 
and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken. 
 
For information concerning special warnings and special precautions for use of Copper-64-labelled 
medicinal products refer to the Summary of Product Characteristics/package leaflet of the medicinal 
product to be radiolabelled. It must be considered that the radiolabelled medicinal product emits high 
intensity Auger electrons. 
 
Regarding the dose for a person in close contact with the patient, this is entirely due to the gamma rays 
(Cuprymina emits 2 gamma rays at 511.0 Kev and 1,345.77 Kev), because β+ and β- emissions have no 
role due to their very short range. 
The Copper-64 gamma dose constant is 3.6 x 10-5 mSv x MBq-1 x h at a distance of 1 meter. Assuming 
the worst case that the whole maximum activity (2,770 MBq) is injected to the patient and Copper-64 is 
labelled to a molecule with infinite biological half-life (no disposal by the patient) the person is 
continuously exposed at a distance of 2 meters. With these assumptions the estimated dose for a person 
in close contact with the patient is 0.46 mSv, which is less than one half of the limit of not exposed 
people (1 mSv/year). 
Special precautions for relatives, carers and hospital staff are provided in section 6.6. 
 
Disappearance of radioactivity 
 
Considering that each MBq of Copper-64 causes a dose rate of 9 nSv/h (at a distance of 2 meters) and 
that the maximum injected activity is of 2,770 MBq, the initial dose rate is 24,930 nSv/h. 
Assuming that the environmental background value is of 150 nSv/h, and requiring that the dose rate due 
to Copper-64 is lower than the environmental background the condition of negligible radioactivity in 
the patient is reached, in practice, 4 days after injection (dose rate 132 nSv/h) as shown in table 1. 
 
 



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Table 1 – Condition of negligible radioactivity in the patients 
Days after 
injection 
(2,770 MBq) 

0 1 2 3 4 5 

Dose rate 
(nSv/h) 24,930 6,727 1,815 490 132 37 

 
4.5 Interactions with other medicinal products and other forms of interaction 
 
No interactions studies of Copper-64 chloride with other medicinal products have been performed. 
The possible use of chelating therapies could interfere with the use of Copper-64-labelled medicinal 
products. 
For information concerning interactions associated with the use of Copper-64-labelled medicinal 
products refer to the Summary of Product Characteristics/package leaflet of the radiolabelled medicinal 
product. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
When an administration of radioactive medicinal products 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. 
Before the use of Copper-64-labelled medicinal products, pregnancy should be excluded using an 
adequate/validated test. 
 
Pregnancy 
 
The use of Copper-64-labelled medicinal products is contraindicated during established or suspected 
pregnancy or when pregnancy has not been excluded (see section 4.3). 
 
Breast-feeding 
 
Before administering 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 the choice of the most appropriate radiopharmaceuticals, bearing in mind the 
secretion of activity in breast milk. If the administration is considered necessary, a breast-feeding 
mother should be advised to stop breast-feeding. 
The duration of stopping will depend on the particular radiolabelled medicinal product. 
Further information concerning the use of Copper-64-labelled medicinal products in pregnancy and 
breast-feeding is specified in the Summary of Product Characteristics of the medicinal product to be 
radiolabelled. 
 
Fertility 
 
According to literature reports, it may be considered that both spermatogenetic and genetic damage in 
male test is are unlikely at the dose of 1,000 MBq. 
Further information concerning the effect on fertility of the use of Copper-64-labelled medicinal 
products is specified in the Summary of Product Characteristics of the medicinal product to be 
radiolabelled. 
 
 
 
 
 



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4.7 Effects on ability to drive and use machines 
 
Effects on ability to drive and to use machines following treatment by Copper-64-labelled medicinal 
products is specified in the Summary of Product Characteristics/package leaflet of the particular 
medicinal product to be radiolabelled. 
 
4.8 Undesirable effects 
 
Adverse reactions following the intravenous administration of Copper-64-labelled medicinal products 
prepared by radiolabelling with Cuprymina, will be dependent on the specific medicinal product being 
used. Such information is supplied in the Summary of Product Characteristics/package leaflet of the 
medicinal product to be radiolabelled.  
For each patient, exposure to ionising radiation must be justifiable on the basis of likely clinical 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 result. 
 
The radiation dose to the patient resulting from exposure after administration may result in higher 
incidence of cancer and mutations. In all cases, it is necessary to ensure that the risks of the radiation 
are less than from the disease itself. 
Exposure to ionising radiation is linked with cancer induction and a potential for development of 
hereditary defects. 
 
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 national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
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: 
- Ca-DTPA (Trisodium calcium diethylenetriaminepentaacetate) or 
- Ca-EDTA (Calcium disodium ethylenediaminetetraacetate) 
 
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. 
 

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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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: various diagnostic radiopharmaceuticals, ATC code: Not yet assigned  
 
The pharmacodynamic properties of Copper-64-labelled medicinal products prepared by radiolabelling 
with Cuprymina, prior to administration, will be dependent on the nature of the medicinal product to be 
radiolabelled. Refer to the Summary of Product Characteristics/package leaflet of the particular 
medicinal product to be radiolabelled.  
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of the studies with 
Cuprymina in all subsets of the paediatric population on grounds of lack of significant therapeutic 
benefit over existing treatments. This waiver does however not extend to any diagnostic or therapeutic 
uses of the medicinal product when linked to a carrier molecule. 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetic properties of Copper-64-labelled medicinal products prepared by radiolabelling 
with Cuprymina, prior to administration, will be dependent on the nature of the medicinal product to be 
radiolabelled. 
Pharmacokinetics of Cuprymina was investigated in mice. Following intravenous administration, at 
the beginning most organs contained an amount of radioactivity which represented their content of 
Copper-64-laden blood. Liver, kidney and the intestinal tract reached their maximal content of 
Copper-64 within the first few hours, and then radioactivity steadily diminished. Part of the decrease 
can be attributed to excretion of Copper-64 into the bile, urine and faeces. 
Blood radioactivity decreased from 60.3 % to 3.4 % after 1 hour, and then it decreased of 1 % after 
6 hours, and increased to 5.6 % and 4.9 % after 12-24 hours. 
Copper chloride (64CuCl2) is distributed mainly in the liver and kidney and the pattern of radioactivity 
in the blood parallels the pattern of radioactivity in the liver. Almost the entire 64CuCl2 rapidly leaves 
the blood and enters the liver and kidney. 
Maximum liver uptake was 4 hours after injection with 57.7 %. Then copper re-emerges in plasma and 
is distributed to other organs. 
 
Pharmacokinetic data on Cuprymina relate to free copper 
 
When the precursor is bound to a carrier molecule the content of radioactive free copper is supposed to 
be less than the stated amounts depending on the carrier used. Relevant data is included in the Summary 
of Product Characteristics of the labelled medicinal products.  
 
5.3 Preclinical safety data  
 
The toxicological properties of Copper-64-labelled medicinal products prepared by radiolabelling with 
Cuprymina prior to administration will be dependent on the nature of the medicinal product to be 
radiolabelled. 
No animal toxicity studies were conducted with Cuprymina. 
Toxicity of copper compounds has been extensively investigated both in human and in animals. Liver, 
gastrointestinal tract and kidney are the target organs for copper toxicity after single and repeated doses 
administration. Many international bodies assessed copper genotoxicity and carcinogenicity concluding 
that there is no conclusive evidence that copper may be mutagenic or carcinogenic The Scientific 
Committee on Food of the European Commission (2003) recommend a Dietary Allowances of 0.9 mg 



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copper/day in adult males and females and established a Tolerable Upper Uptake level of 5 mg/day, 
allowing a huge safety margin in comparison to copper amount administered by Cuprymina. 
Non-clinical data reveal no special hazard for humans based on available published data. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hydrochloric acid (0.1 N). 
Water for injections. 
 
6.2 Incompatibilities 
 
Radiolabelling of carrier molecules, such as peptides, monoclonal antibodies, or other substrates, with 
Copper (64Cu) chloride is very sensitive to the presence of trace metal impurities. 
It is important that all glassware, syringe needles etc, used for the preparation of the radiolabelled 
compound are thoroughly cleaned to ensure freedom from such trace metal impurities. Only syringe 
needles (for example, non-metallic) with proven resistance to dilute acid should be used to minimise 
trace metal impurity levels. 
 
6.3 Shelf life 
 
48 hours from date and time of End of Synthesis (EOS). 
 
6.4 Special precautions for storage 
 
Store in the original package that provides protection from radiation. 
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive 
materials. 
 
6.5 Nature and contents of container 
 
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. 
 
6.6 Special precautions for disposal and other handling 
 
Cuprymina is not intended for direct use in patients. 
 
Cuprymina is a sterile solution. 
 
General warning  
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.  
 



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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. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
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 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/12/784/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 august 2012 
Date of latest renewal: 19 july 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
11. DOSIMETRY 
 
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 Copper-
64 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. 



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Table 2: Absorbed dose per unit activity administered  

 
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. 
 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Before use, packaging and radioactivity must be checked. Activity may be measured using an ionisation 
chamber. Copper-64 is a beta emitter. Activity measurements using an ionisation chamber are very 
sensitive to geometric factors and, therefore, should be performed only under geometric conditions 
which have been appropriately validated. 
Usual precautions regarding sterility and radioactivity must be respected. 
The vial should never be opened and must be kept inside its shielded container. The medicinal product 
must be aseptically withdrawn through the stopper using sterilised single-use needle and syringe after 
disinfecting the stopper. 
Appropriate aseptic precautions must be taken, in order to maintain the sterility of Cuprymina and to 
maintain sterility throughout the labelling procedures. 
 

absorbed dose per unit activity administered 
(mGy/MBq) 

organ adult male (70 kg) 
adult female 
(60 kg) 15 years 10 years 5 years 1 years 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 years newborn 
  0.0962 0.0712 0.168 0.854 1.05 1.56 2.73 



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The administration of radioactive medicinal products 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 medicinal product or waste material must be disposed of in accordance with local 
requirements. 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

http://www.ema.europa.eu/


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ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
ACOM S.r.l. (Advanced Center Oncology Macerata) 
Località Cavallino 
IT-62010 MONTECOSARO (MC) 
Italy 
 
SPARKLE S.r.l 
Contrada Calò, snc  
IT-73042 Casarano (LE) 
Italy 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set out 
in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
TUNGSTEN OR LEAD CONTAINER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cuprymina 925 MBq/mL radiopharmaceutical precursor, solution. 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Copper (64Cu) chloride, 925 MBq/mL at calibration time (01h00 a.m. CET), corresponding to 
0.25 micrograms (64Cu). The calibration time is set between the EOS time and the Expiry time. 
Specific activity ≥ 3,700 MBq Cu-64/micrograms of copper. 
 
 
3. LIST OF EXCIPIENTS 
 
Hydrochloric acid (0.1 N). 
Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Volume: {Z} mL 
Activity: (Y) MBq  Calibration time: {DD/MM/YYYY} 01h00 a.m. CET 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Not intended for direct administration to patients. 
For in vitro radiolabelling. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children.  
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

 
 
 
8. EXPIRY DATE 
 
Shelf-life: 48 hours from date/time of EOS. 

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EXP {DD/MM/YYYY} hh:mm CET 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package that provides protection from radiation, according to local regulation. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Dispose in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
MAH: 
 
A.C.O.M. -ADVANCED CENTER ONCOLOGY MACERATA -S.R.L. 
Località Cavallino 39 A/B 
62010 Montecosaro 
 
Manufacturer:  
ACOM S.r.l. Italy  
 
SPARKLE S.r.l  Italy 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/784/001 
 
 
13. BATCH NUMBER 
 
Batch 
Ref. N° 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subjects to medical prescription. 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable.  



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18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
TYPE I VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Cuprymina 925 MBq/mL radiopharmaceutical precursor, solution. 
Copper (64Cu) chloride 
 
 
2. METHOD OF ADMINISTRATION 
 
For in vitro radiolabelling. 
Not intended for direct administration to patients. 
 
 
3. EXPIRY DATE 
 
EXP {DD/MM/YYYY} (hh:mm CET) 
 
 
4. BATCH NUMBER 
 
Batch  
Ref. N° 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Volume: {Z} mL 
Activity: {Y}________MBq  Cal.: {DD/MM/YYYY} 01h00 a.m. CET 
 
 
6. OTHER 
 

 
 
Manufacturer: 
 
ACOM S.r.l. 
 
SPARKLE S.r.l  
 

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B. PACKAGE LEAFLET 



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Package leaflet: Information for the patient 
 

Cuprymina 925 MBq/mL radiopharmaceutical precursor, solution 
Copper (64Cu) chloride 

 
Read all of this leaflet carefully before you are given the medicine combined with Cuprymina 
because it contains important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your nuclear medicine doctor who will supervise the 

procedure. 
- If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
 
1. What Cuprymina is and what it is used for  
2. What you need to know before the medicine radiolabelled with Cuprymina is used  
3. How the medicine radiolabelled with Cuprymina is used  
4. Possible side effects  
5. How to store Cuprymina  
6. Contents of the pack and other information 
 
 
1. What Cuprymina is and what it is used for 
 
Cuprymina is not a medicine and it is not intended to be used on its own.  
 
Cuprymina is a type of medicinal product called a radiopharmaceutical precursor. It contains the 
active substance copper (64Cu) chloride. Copper-64 is a radioactive form of the chemical element 
copper, which emits the radiation needed for certain procedures that may be carried out on you. 
 
Cuprymina is used for radiolabelling, a technique in which a substance is tagged (radiolabelled) with a 
radioactive compound. Cuprymina is used to label certain medicines that have been specially 
developed for use with the active substance copper (64Cu) chloride. These medicines act as a carrier to 
take the radioactivity to where it is needed. These may be substances that have been designed to 
recognise a particular type of cell in the body, including tumour cells.  
 
The use of Copper-64-labelled medicines involves exposure to small amounts of radioactivity. Your 
doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain 
from the procedure with the radiopharmaceutical outweighs the risk from radiation. 
 
Please refer to the package leaflet of the medicine that is to be radiolabelled with Cuprymina.  
 
 
2. What you need to know before the medicine radiolabelled with Cuprymina is used 
 
The medicine radiolabelled with Cuprymina must not be used: 
- If you are allergic to copper or any of the other ingredients of this medicine listed in section 6. 
- If you are pregnant or believe you may be pregnant. 
 
Warnings and precautions  
Talk to your nuclear medicine doctor before using the medicine that is radiolabelled with Cuprymina. 
Cuprymina 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 by the user in a manner which satisfies both radiation safety 
and pharmaceutical quality requirements. 



21 
 

It must be considered that the radiolabelled medicinal product emits high intensity Auger electrons. 
The condition of negligible radioactivity in the patient is reached, in practice, 4 days after injection. 
 
Children and adolescents 
Medicines radiolabelled with Cuprymina should not be used in children and adolescents up to 18 years. 
 
Other medicines and medicines radiolabelled with Cuprymina 
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other 
medicines since they may interfere with the interpretation of the images. 
It is not known whether copper (64Cu) chloride may interact with other medicines as specific studies 
have not been carried out. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your nuclear medicine doctor for advice before you are given medicines radiolabelled with 
Cuprymina. 
 
You must inform the nuclear medicine doctor before the administration of medicines radiolabelled 
with Cuprymina if there is a possibility you might be pregnant, if you have missed your period or if 
you are breast-feeding.  
When in doubt, it is important to consult your nuclear medicine doctor who will supervise the 
procedure. 
 
If you are pregnant 
Medicines radiolabelled with Cuprymina must not be administered if you are pregnant. 
 
If you are breast-feeding  
You will be asked to stop breast-feeding if you need to receive a medicine radiolabelled with 
Cuprymina. 
Please ask your nuclear medicine doctor when you can resume breast-feeding. 
 
Driving and using machines 
There could be effects on your ability to drive and to use machines due to the medicine used in 
combination with Cuprymina. Please read the package leaflet of that medicine carefully. 
 
 
3. How the medicine radiolabelled with Cuprymina is used 
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products. Medicines 
radiolabelled with Cuprymina will only be used in special, controlled areas. This medicinal product will 
only be handled and given to you by people who are trained and qualified to use it safely. These persons 
will take special care for the safe use of this medicinal product and will keep you informed of their 
actions. 
 
The nuclear medicine doctor supervising the procedure will decide on the quantity of medicine 
radiolabelled with Cuprymina to be used in your case. It will be the smallest quantity necessary to 
achieve the appropriate outcome, depending on the co-administered medicine and its intended use.  
 
Administration of the medicine radiolabelled with Cuprymina and conduct of the procedure 
Cuprymina must be used only in combination with another medicine which has been specifically 
developed and authorised for being combined with Cuprymina, and will be administered subsequently. 
 
Duration of the procedure 
Your nuclear medicine doctor will inform you about the usual duration of the procedure before the 
administration of the medicine radiolabelled with Cuprymina. 
 
 



22 
 

After administration of the medicine radiolabelled with Cuprymina has been performed 
The nuclear medicine doctor will inform you if you need to take any special precautions after receiving 
the medicine radiolabelled with Cuprymina. Contact your nuclear medicine doctor if you have any 
questions. 
 
If you have been given more medicine radiolabelled with Cuprymina than you should  
Since the medicine radiolabelled with Cuprymina is handled by a nuclear medicine doctor under strictly 
controlled conditions, there is only a very small chance of possible overdose. However, in the case of an 
overdose, you will receive the appropriate treatment. 
 
Should you have any further question on the use of Cuprymina, please ask the nuclear medicine doctor 
who supervises the procedure. 
 
 
4. Possible side effects 
 
Like all medicines, the medicine radiolabelled with Cuprymina can cause side effects, although not 
everybody gets them. 
 
After the medicine radiolabelled with Cuprymina is administered, it will deliver certain amounts of 
ionising radiation (radioactivity) which can induce a certain risk of cancer and development of 
hereditary defects. In all cases, the risks of the radiation should be less than from the disease itself. 
 
For more information, refer to the package leaflet of the particular medicine to be radiolabelled. 
 
If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side 
effects not listed in this leaflet. 
 
Reporting of side effects 
If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system listed 
in Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5.  How to store Cuprymina  
 
Keep this medicine out of the sight and reach of children. 
 
The following information is intended for the specialist only.  
Do not use this medicine after the expiry date and time which are stated on the label after EXP. 
Cuprymina will be stored in the original package that provides protection from radiation. 
 
You will not have to store this medicinal product. Cuprymina is stored under the responsibility of the 
specialist in appropriate premises. Storage of radiopharmaceuticals will be in accordance with national 
regulation on radioactive materials.  
 
 
6. Contents of the pack and other information 
 
What Cuprymina contains 
- The active substance is copper (64Cu) chloride. Each mL of solution contains 925 MBq at 

calibration time (01h00 a.m. CET Central European Time), corresponding to at least 
0.25 micrograms of copper-64. One vial contains from 925 to 2,770 MBq (corresponding to 0.25-
0.75 micrograms of copper-64). (MBq: mega Becquerel, Becquerel is the unit in which 
radioactivity is measured) 

- The other ingredients are hydrochloric acid (0.1 N) and water for injections. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


23 
 

 
What Cuprymina looks like and contents of the pack 
Cuprymina is presented as a clear, and colourless solution filled in a 10 mL glass vial. 
The volume of one vial ranges from 1 to 3 mL solution (corresponding to 925 to 2,770 MBq at 
calibration time).  
This volume depends on the quantity of medicine combined with Cuprymina required for 
administration by the nuclear medicine doctor.  
Each pack contains 1 vial in a tungsten or lead container.  
 
Marketing Authorisation Holder 
 
 
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 
 
 
Manufacturer  
ACOM S.r.l. 
Località Cavallino 
62010 Montecosaro (MC) – Italy 
 
SPARKLE S.r.l 
Contrada Calò, snc  
73042 Casarano (LE) - Italy 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last revised in MM/YYYY 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
----------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for medical or healthcare professionals only: 
 
The complete Summary of Product Characteristics (SmPC) of Cuprymina is provided as a separate 
document in the medicinal product pack, with the objective to provide healthcare professionals with 
other additional scientific and practical information about the use of this medicinal product. 
 
Please refer to the SmPC. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET