CUPRYMINA Radiopharmaceutical precursor, solution Ref.[11035] Active ingredients: Copper ⁶⁴Cu chloride

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 × 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.

Table 1. Condition of negligible radioactivity in the patients:

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.

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.

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.

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.

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.