Summary of medicine characteristics - YTRACIS RADIOPHARMACEUTICAL PRECURSOR SOLUTION 1850 MBQ/ML
YTRACIS radiopharmaceutical precursor, solution.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of sterile solution contains 1.850 GBq Yttrium (90Y) chloride, at the date of calibration, corresponding to 92 ng of Yttrium.
One vial contains 0.925 to 3.700 GBq (see section 6.5).
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Radiopharmaceutical precursor, solution.
Clear, colourless solution, free of particulate matter.
4.1 Therapeutic indications
To be used only for the radiolabelling of carrier molecules which have been specifically developed and authorised for radiolabelling with this radionuclide.
Radiopharmaceutical precursor – Not intended for direct application to patients.
4.2 Posology and method of administration
YTRACIS is only to be used by specialists with the appropriate experience.
The quantity of YTRACIS required for radiolabelling and the quantity of Yttrium (90Y)-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.
YTRACIS is intended for in vitro radiolabelling of medicinal products, which are subsequently administered by approved route.
4.3 Contraindications
Do not administer YTRACIS directly to the patient.
YTRACIS is contraindicated in the following cases:
– Hypersensitivity to the active substance or to any of the excipients.
– Established or suspected pregnancy or when pregnancy has not been excluded (see section 4.6).
For information on contraindications to particular Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with YTRACIS, refer to the Summary of Product Characteristics/package leaflet of the particular medicinal product to be radiolabelled.
4.4 Special warnings and precautions for use
The content of the vial of YTRACIS 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.
Radioactive medicinal products should be received, used and administered only by authorised persons in designated clinical settings and receipt, storage, use, transfer and disposal are subject to the regulations and appropriate licences of the competent authorities.
Radioactive medicinal products should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements.
For information concerning special warnings and precautions for use of Yttrium (90Y)-labelled medicinal products refer to the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabelled.
Particular care should be taken when administering radioactive medicinal products to children and adolescents.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
For information concerning interactions associated with the use of Yttrium (90Y)-labelled medicinal products refer to the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabelled.
4.6 Fertility, pregnancy and lactation
YTRACIS is contraindicated during established or suspected pregnancy or when pregnancy has not been excluded (see section 4.3 Contraindications).
When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Alternative techniques which do not involve ionising radiation should always be considered.
Radionuclide procedures carried out in pregnant women also involve radiation doses to the foetus.
The absorbed dose to the uterus following administration of Yttrium (90Y)-labelled medicinal products is dependent on the specific medicinal product being radiolabelled and is to be specified in the Summary of Product Characteristics/ package leaflet of the medicinal product to be radiolabelled.
Before administering a radioactive medicinal product to a mother who is breast-feeding, consideration should be given to whether the administration could be reasonably delayed until the mother has ceased breastfeeding. If the administration cannot be delayed, a lactating mother should be advised to stop breastfeeding.
For information concerning the use of Yttrium (90Y)-labelled medicinal products in pregnancy and lactation refer to the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabelled.
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.
Effects on ability to drive or use machines following treatment by Yttrium (90Y)-labelled medicinal products will be specified in the Summary of Product Characteristics/package leaflet of the particular medicinal product to be radiolabelled.
4.8 Undesirable effects
4.8 Undesirable effectsPossible side effects following the intravenous administration of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with YTRACIS, will be dependent on the specific medicinal product being used. Such information will be 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 therapeutic result.
The radiation dose resulting from therapeutic exposure 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.
The presence of free Yttrium (90Y) chloride in the body after an inadvertent administration of Ytracis will lead to increase bone marrow toxicity and haematopoetic stem cell damage. Therefore, in case of an inadvertent administration of Ytracis, the radiotoxicity for the patient must be reduced by immediate (i.e. within 1 hour) 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 Ytracis for radiolabelling of carrier molecules for therapeutic purposes: Ca-DTPA (Trisodium calcium diethylenetriaminepentaacetate) or Ca-EDTA (Calcium disodium ethylenediaminetetraacetate)
These chelating agents suppress yttrium radiotoxicity by an exchange between the calcium ion and the yttrium 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 dextrose, or normal saline).
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 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 damage to the blood marrow.
The toxicity of the free Yttrium (90Y) 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: Not applicable ATC code: Not applicable
Yttrium (90Y) chloride is produced by decay of its radioactive precursor Strontium (90Sr). It decays by emission of beta radiation of 2.281 MeV (99.98 %) of maximal energy to stable Zirconium (90Zr).
90Y-yttrium has a half-life of 2.67 days (64.1 hours).
The pharmacodynamic properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with YTRACIS, 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.
5.2 Pharmacokinetic properties
The pharmacokinetic properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with YTRACIS, prior to administration, will be dependent on the nature of the medicinal product to be radiolabelled.
In the rat, following intravenous administration, Yttrium (90Y) chloride is rapidly cleared from the blood. At 1 and 24 hours, blood radioactivity decreases from 11 % to 0.14 % of the administered activity. The two main organs where Yttrium (90Y) chloride distributes are the liver and bones. In the liver, 18 % of the injected activity is taken up 5 min after injection. Liver uptake decreases then to 8.4 % 24 hours after injection. In bone, percentage of injected activity increases from 3.1 % at 5 min to 18 % at 6 hours and then decreases with time. Faecal and urinary elimination is slow: about 13 % of the administered activity is eliminated in 15 days.
5.3 Preclinical safety data
5.3 Preclinical safety dataThe toxicological properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with YTRACIS prior to administration, will be dependent on the nature of the medicinal product to be radiolabelled.
There are no data available on the toxicity of Yttrium (90Y) chloride nor on its effects on reproduction in animals or its mutagenic or carcinogenic potential.
6.1 List of excipients
Hydrochloric acid 30 % Water for injections
6.2 Incompatibilities
Radiolabelling of carrier molecules, such as monoclonal antibodies, peptides or other substrates, with Yttrium (90Y) 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 medicinal product 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
7 days from the date/hour of manufacture.
6.4 Special precautions for storage
Store in the original package.
Storage should be in accordance with local regulations for radioactive substances.
6.5 Nature and contents of container
Colourless Type I glass 2-ml vial, closed with Teflon-coated bromobutyl rubber stopper and aluminium overseal.
1 vial contains 0.5 to 2 ml (corresponding to 0.925 to 3.700 GBq calibrated three or four days after the manufacturing date) depending on the ordered radioactivity.
The vial is supplied in a lead pot of appropriate thickness.
6.6 Special precautions for disposal
6.6 Special precautions for disposalThe 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 product or waste material should be disposed of in accordance with local requirements.
See section 12, for detailed instructions of product preparation.
7 MARKETING AUTHORISATION HOLDER
CIS bio international
Boîte Postale 32
F-91192 GIF-SUR-YVETTE CEDEX
FRANCE
8 MARKETING AUTHORISATION NUMBER(S)
PLGB 11876/0026