V04CXN1 • yttrium hydrochloride • Various | Other diagnostic agents
Yttrium hydrochloride is a chemical compound containing yttrium, a rare earth element from the lanthanide group. It is primarily used in industrial and medical applications, such as the production of phosphorescent materials, lasers, and in cancer treatments. In medicine, yttrium isotopes, such as yttrium-90, are used in radioembolization therapies for treating liver cancer and other tumors.
Yttrium hydrochloride is used as a precursor in the synthesis of other yttrium compounds and in advanced materials research. In medical applications, the compound is handled with care to minimize radiation exposure and ensure the safety of patients and medical personnel.
Side effects associated with yttrium use in medicine depend on the specific form and application. In the case of radioembolization, adverse reactions may include fatigue, nausea, abdominal pain, and, in rare cases, liver function impairment.
Handling yttrium hydrochloride requires strict adherence to safety protocols, especially in medical applications involving radiation. This compound plays a significant role in various fields, from technology to medicine, contributing to the development of innovative solutions for treating severe diseases.
Substance: yttrium hydrochloride
Date of last drug list: 01-07-2013
Commercial code: W42386001
Concentration: 1.850 GBq / ml
Pharmaceutical form: solution
Quantity: 1
Product type: original
Prescription restrictions: S - Medicines prescription reserved for use in certain specialized fields.
Manufacturer: CIS BIO - FRANTA
Holder:
Number: EU/1/03/250/001
YTRACIS radiopharmaceutical precursor, solution.
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.
Radiopharmaceutical precursor, solution.
Clear, colourless solution, free of particulate matter.
To be used only for the radiolabelling of carrier molecules which have been specifically developedand authorised for radiolabelling with this radionuclide.
Radiopharmaceutical precursor - Not intended for direct application to patients.
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)-labelledmedicinal product that is subsequently administered will depend on the medicinal productradiolabelled and its intended use. Refer to the Summary of Product Characteristics/package leaflet ofthe particular medicinal product to be radiolabelled.
YTRACIS is intended for in vitro radiolabelling of medicinal products, which are subsequentlyadministered by approved route.
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 preparedby radiolabelling with YTRACIS, refer to the Summary of Product Characteristics/package leaflet ofthe particular medicinal product to be radiolabelled.
The content of the vial of YTRACIS is not to be administered directly to the patient but must be usedfor the radiolabelling of carrier molecules, such as monoclonal antibodies, peptides or othersubstrates.
Radioactive medicinal products should be received, used and administered only by authorised personsin designated clinical settings and receipt, storage, use, transfer and disposal are subject to theregulations and appropriate licences of the competent authorities.
Radioactive medicinal products should be prepared by the user in a manner which satisfies bothradiation safety and pharmaceutical quality requirements.
For information concerning special warnings and precautions for use of Yttrium (90Y)-labelledmedicinal products refer to the Summary of Product Characteristics/package leaflet of the medicinalproduct to be radiolabelled.
Particular care should be taken when administering radioactive medicinal products to children andadolescents.
No interaction studies have been performed.
For information concerning interactions associated with the use of Yttrium (90Y)-labelled medicinalproducts refer to the Summary of Product Characteristics/package leaflet of the medicinal product tobe radiolabelled.
YTRACIS is contraindicated during established or suspected pregnancy or when pregnancy has notbeen 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 shouldbe assumed to be pregnant until proven otherwise. Alternative techniques which do not involveionising 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 medicinalproducts is dependent on the specific medicinal product being radiolabelled and is to be specified inthe 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, considerationshould be given to whether the administration could be reasonably delayed until the mother hasceased breastfeeding. If the administration cannot be delayed, a lactating mother should be advised tostop breastfeeding.
For information concerning the use of Yttrium (90Y)-labelled medicinal products in pregnancy andlactation refer to the Summary of Product Characteristics/package leaflet of the medicinal product tobe radiolabelled.
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 medicinalproducts will be specified in the Summary of Product Characteristics/package leaflet of the particularmedicinal product to be radiolabelled.
Possible side effects following the intravenous administration of Yttrium (90Y)-labelled medicinalproducts prepared by radiolabelling with YTRACIS, will be dependent on the specific medicinalproduct 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 activityadministered must be such that the resulting radiation dose is as low as reasonably achievable bearingin mind the need to obtain the intended therapeutic result.
The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer andmutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from thedisease itself.
Exposure to ionising radiation is linked with cancer induction and a potential for development ofhereditary defects.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
The presence of free Yttrium (90Y) chloride in the body after an inadvertent administration of Ytraciswill lead to increase bone marrow toxicity and haematopoetic stem cell damage. Therefore, in case ofan inadvertent administration of Ytracis, the radiotoxicity for the patient must be reduced byimmediate (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 forradiolabelling 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 theyttrium 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 over3-4 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 radionuclideis circulating in or available to tissue fluids and plasma. However, a post-exposure interval >1 hourdoes 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 actionsimmediately 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 bodyduring therapy could be reduced by post-administration of chelating agents.
Pharmacotherapeutic group: Not applicable
ATC code: Not applicable
Yttrium (90Y) chloride is produced by decay of its radioactive precursor Strontium (90Sr). It decays byemission 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 byradiolabelling with YTRACIS, prior to administration, will be dependent on the nature of themedicinal product to be radiolabelled. Refer to the Summary of Product Characteristics/packageleaflet of the particular medicinal product to be radiolabelled.
The pharmacokinetic properties of Yttrium (90Y)-labelled medicinal products prepared byradiolabelling with YTRACIS, prior to administration, will be dependent on the nature of themedicinal product to be radiolabelled.
In the rat, following intravenous administration, Yttrium (90Y) chloride is rapidly cleared from theblood. At 1 and 24 hours, blood radioactivity decreases from 11 % to 0.14 % of the administeredactivity. The two main organs where Yttrium (90Y) chloride distributes are the liver and bones. In theliver, 18 % of the injected activity is taken up 5 min after injection. Liver uptake decreases then to8.4 % 24 hours after injection. In bone, percentage of injected activity increases from 3.1 % at 5 minto 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.
The toxicological properties of Yttrium (90Y)-labelled medicinal products prepared by radiolabellingwith YTRACIS prior to administration, will be dependent on the nature of the medicinal product to beradiolabelled.
There are no data available on the toxicity of Yttrium (90Y) chloride nor on its effects on reproductionin animals or its mutagenic or carcinogenic potential.
Hydrochloric acid 30 %
Water for injections
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 radiolabelledmedicinal product are thoroughly cleaned to ensure freedom from such trace metal impurities. Onlysyringe needles (for example non-metallic) with proven resistance to dilute acid should be used tominimise trace metal impurity levels.
7 days from the date/hour of manufacture.
Store in the original package.
Storage should be in accordance with local regulations for radioactive substances.
Colourless Type I glass 2-ml vial, closed with Teflon-coated bromobutyl rubber stopper andaluminium overseal.
1 vial contains 0.5 to 2 ml (corresponding to 0.925 to 3.700 GBq calibrated three or four days after themanufacturing date) depending on the ordered radioactivity.
The vial is supplied in a lead pot of appropriate thickness.
The administration of radioactive medicinal products creates risks for other persons from externalradiation or contamination from spills of urine, vomiting, etc. Radiation protection precautions inaccordance 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.
CIS bio international
Boîte Postale 32
F-91192 GIF-SUR-YVETTE CEDEX
FRANCE
EU/1/03/250/001
Date of the first authorisation: 24/03/2003
Date of the last renewal: 24/03/2008
The radiation dose received by the various organs following administration of a Yttrium (90Y)-labelled medicinal product will be dependent on the specific pharmaceutical being radiolabelled.
Information on radiation dosimetry of each different medicinal product following administration ofthe radiolabelled preparation will be available in the Summary of Product Characteristics/packageleaflet of the particular medicinal product to be radiolabelled.
The dosimetry table below is presented in order to evaluate the contribution of non-conjugated
Yttrium (90Y) to the radiation dose following the administration of Yttrium (90Y)-labelled medicinalproduct or resulting from an accidental intravenous injection of YTRACIS.
The dosimetry estimates were based on a rat biodistribution study and the calculations were effectedin accordance with MIRD/ICRP 60 recommendations. Timepoints for measurements were5 minutes, 1 hour, 6 hours, 1 day, 4 days and 15 days.
Organ doses (mGy/MBq injected) and effective dose (Sv/GBq injected).
Absorbed dose per unit activity administered(mGy/MBq)
Adult male Adult female
Organ 15 years 10 years 5 years 1 year New Born70 kg 57 kg
Kidneys 5.06 5.50 6.10 8.75 13.0 24.1 66.1
Liver 2.41 3.29 3.29 5.20 7.89 15.8 38.1
Bladder 2.11 2.78 2.78 4.31 6.87 13.5 35.8
Ovaries --- 0.88 0.92 3.1 5.6 13.6 29.6
Uterus --- 0.29 0.3 5.7 8.8 16.3 6.15
Spleen 0.85 1.04 1.27 2.02 3.23 6.12 17.1
Bone 0.30 0.29 0.29 0.53 0.98 1.37 2.41
Heart 0.26 0.33 0.34 0.54 0.87 1.60 3.18
Lungs 0.11 0.14 0.17 0.24 0.37 0.75 2.13
Intestines 0.10 0.11 0.13 0.23 0.39 0.78 2.02
Muscles 0.05 0.08 0.09 0.20 0.68 1.36 1.79
Testes 0.01 --- 0.03 0.23 0.26 0.36 0.51
Effective dose (Sv/1 GBq administered)
Adult male Adult female 15 years 10 years 5 years 1 year New Born0.65 0.70 0.74 1.50 2.50 5.42 12.8
For this product, the effective dose resulting from an intravenously injected activity of 1 GBq is700 mSv for a 57-kg female adult and 650 mSv for a 70-kg male adult.
Before use, packaging and radioactivity should be checked. Activity may be measured using anionisation chamber. Yttrium (90Y) is a beta pure emitter. Activity measurements using an ionisationchamber are very sensitive to geometric factors and therefore should be performed only undergeometric conditions which have been appropriately validated.
Usual precautions regarding sterility and radioactivity should be respected.
The vial should never be opened and must be kept inside its lead shielding. The product should beaseptically withdrawn through the stopper using sterilised single use needle and syringe afterdisinfection of the stopper.
Appropriate aseptic precautions should be taken, complying with the requirements of Good
Pharmaceutical Manufacturing Practice, in order to maintain the sterility of YTRACIS and tomaintain sterility throughout the labelling procedures.
Any unused product or waste material should 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.
