Summary of medicine characteristics - Yttriga
1. NAME OF THE MEDICINAL PRODUCT
Yttriga radiopharmaceutical precursor, solution.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml sterile solution contains 0.1–300 GBq Yttrium (90Y) on the reference date and time (corresponding to 0.005–15 micrograms of Yttrium [90Y]) (as Yttrium [90Y] chloride).
Each 3ml vial contains 0.1–300 GBq, corresponding to 0.005–15 micrograms of Yttrium (90Y), at reference date and time. The volume is 0.02–3 ml.
Each 10ml vial contains 0.1–300 GBq, corresponding to 0.005–15 micrograms of Yttrium (90Y), at reference date and time. The volume is 0.02–5 ml.
The theoretical specific activity is 20 GBq/microgram of Yttrium (90Y) (see section 6.5).
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).
Yttrium (90Y) has a half-life of 2.67 days (64.1 hours).
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Radiopharmaceutical precursor, solution.
Clear colourless solution, free of particulate matter.
4. CLINICAL PARTICULARS4.1 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 use in patients.
4.2 Posology and method of administration
Yttriga is only to be used by specialists experienced with in vitro radiolabelling.
Posology
The quantity of Yttriga 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.
Method of administration
Yttriga is intended for in vitro labelling of medicinal products which are subsequently administered by the approved route.
Further information on the preparation of the product is given in section 12.
4.3 Contraindications
Do not administer Yttriga directly to the patient.
Yttriga is contraindicated in the following cases:
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– Hypersensitivity to Yttrium (90Y) chloride or to any of the excipients
Yttrium (90Y)-labelled medicinal products are contraindicated in the following case:
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– 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 Yttriga refer the Summary of Product Characteristics/package leaflet of the particular medicinal product to be radiolabelled.
4.4 Special warnings and precautions for use
The contents of the vial of Yttriga 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.
Radiopharmaceuticals 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.
Radiopharmaceuticals should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements.
For information concerning special warnings and special 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 (from 2 to 16 years old).
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies of Yttrium (90Y) chloride with other medicinal products have been performed, because Yttriga is a precursor solution for radiolabelling medicinal products.
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
Women of childbearing potential
Women of childbearing potential have to use effective contraception during and after treatment.
Pregnancy
Yttrium (90Y)-labelled medicinal products are contraindicated in established or suspected pregnancy or when pregnancy has not been excluded (see section 4.3).
Breast-feeding
Before administering a radioactive medicinal product to a mother who is breast-feeding, consideration should be given to whether the investigation could be reasonably delayed until the mother has ceased breast-feeding. If the administration cannot be delayed, a lactating mother should be advised to stop breast-feeding.
Further information concerning the use of a Yttrium (90Y)-labelled medicinal products in pregnancy and breast-feeding is specified in the Summary of Product Characteristics of the medicinal product to be radiolabelled.
Fertility
Further information concerning the use of a Yttrium (90Y)-labelled medicinal concerning fertility is specified in the Summary of Product Characteristics of the medicinal product to be radiolabelled.
4.7 Effects on ability to drive and use machines
Effects on ability to drive and to use machines following treatment by Yttrium (90Y)-labelled medicinal products will be specified in the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabelled.
4.8 Undesirable effects
Possible adverse reactions following the intravenous administration of a Yttrium (90Y)-labelled medicinal product prepared by radiolabelling with Yttriga, 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.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects.
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.
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
4.9 Overdose
The presence of free Yttrium (90Y) chloride in the body after an inadvertent administration of Yttriga will lead to increased bone marrow toxicity and haematopoietic stern cell damage.
Therefore, in case of an inadvertent administration of Yttriga, 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 Yttriga for labelling of carrier molecules for therapeutic purposes:
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– Ca-DTPA (Trisodium calcium diethylenetriaminepentaacetate) or
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– 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 PROPERTIES5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other therapeutic radiopharmaceuticals, ATC code: V10X.
The pharmacodynamic properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with Yttriga, 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 Yttriga, 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 11.0 % 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 31 % of the administered activity is eliminated in 15 days.
5.3 Preclinical safety data
The toxicological properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabelling with Yttriga 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. PHARMACEUTICAL PARTICULARS6.1 List of excipients
Hydrochloric acid (0.04 M)
6.2 Incompatibilities
Radiolabelling of medicinal products, 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
Up to 12 days from the date of manufacture.
6.4 Special precautions for storage
Storage should be in accordance with national regulation on radioactive material.
6.5 Nature and contents of container
Colourless type I glass vial of 3 ml with a V-shapped bottom or a colourless type I glass vial of 10 ml with a flat bottom with a silicon stopper, closed with an aluminium seal.
Pack size: 1 vial
Not all presentations may be marketed.
6.6 Special precautions for disposal
The vial may contain high pressure due to radiolysis (see section 12).
7. MARKETING AUTHORISATION HOLDER
Eckert & Ziegler Radiopharma GmbH
Robert-Rossle-Str. 10
D-13125 Berlin
Germany
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/05/322/001 (3 ml V-shaped vial)
EU/1/05/322/002 (10 ml flat bottom vial)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 19/01/2006
Date of renewal: 06/01/2011