Summary of Product Characteristics (SmPC) - Kryptoscan Generator
1 NAME OF THE MEDICINAL PRODUCT
KryptoScanTM generator
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Rubidium (81Rb) bound as ion to a cation exchange resin which is in equilibrium with the daughter-product Krypton (81m Kr )and serves as a generator for Krypton (81mKr) gas.
The generator is available with activities ranging between 75-740 MBq
Physical characteristics
Rubidium (81Rb) decays with a physical half-life of 4.58 hours to its metastable daughter-product Krypton (81mKr) thus generating this short-lived radionuclide with a half-life of 13 seconds. Krypton (81mKr) decays by isometric transition to Krypton (81Kr), emitting pure gamma radiation of 0.190 MeV which is internally converted. 81Kr decays to stable 81Br with a halflife of T½ = 2.1 x 105 years.
3 PHARMACEUTICAL FORM
Radionuclide generator.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
- Investigation of pulmonary ventilation, according to the low radiation dose, this product can be especially recommended for paediatric examination.
- Combined with a pulmonary perfusion scintigraphy for diagnosis of pulmonary embolism.
- Pulmonary ventilation (81mKr) / perfusion (99Tc-macroaggregation) studies are possible because of the different spectrometric windows of 81mKr and 99mTc.
4.2 Posology and method of administration
Krypton images are acquired during the continuous inhalation of the short lived and otherwise inert radioactive gas, Krypton (81mKr). This is eluted with humidified air from a rubidium generator and administered to the patient through a face mask or airway.
In general adequate imaging is achieved when 200.000-350.000 counts are accumulated per gamma camera image. This corresponds to approx. 18 MBq/kg body weight. Most investigation requires a number of views = 4 to 6.
The activities for children may be calculated according to the following equation:
Activity-child (MBq) = Activity-adult (MBq) x body weight (kg)
70 (kg)
Continuous inhalation is stopped upon acquisition of approx. 300.000 counts per gamma camera image.
4.3 Contraindications
None known.
4.4 Special warnings and precautions for use
Radiopharmaceuticals may be used and administered only by authorised persons.
4.5 Interaction with other medicinal products and other forms of interaction
Diazepam in sedative doses and general anaesthetic agents may affect the distribution of radioactive gases in the lung by slightly shifting the activity to the lung apex and reducing basal accumulation.
4.6 Fertility, Pregnancy and lactation
When it is necessary to administer radioactive medicinal product 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. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation should be considered.
Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only imperative investigations should be carried out during pregnancy, when the likely benefit exceeds the risk incurred by mother and foetus.
Before administering a radioactive medicinal product to a mother who is breast-feeding consideration should be given as to whether the investigation could reasonably delayed until the mother has ceased breast-feeding and as to whether the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretory activity in breast milk. If administration of Krypton (81mKr) gas is considered necessary, however, breast-feeding need not be specifically interrupted
4.7 Effects on ability to drive and use machines
Effects on the ability to drive or to operate machines have not been described.
4.8 Undesirable effects
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 diagnostic or therapeutic result.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. For diagnostic nuclear medicine investigations the current evidence suggests that these adverse effects will occur with negligible frequency because of the low radiation dose incurred.
For most diagnostic investigations using a nuclear medicine procedure the radiation dose delivered (EDE) is less than 20 mSv. Higher doses may be justified in some clinical circumstances.
No adverse/undesirable effects have been reported for this agent.
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: Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Also, in the unusual event of radiation overdose caused by an unrequired but prolonged period of krypton gas inhalation, due to the rapid washout from the lungs during normal ventilation, patients need only be removed from the source of radiation to a fresh and uncontaminated atmosphere.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC-Code: V09E X (Other respiratory system diagnostic radiopharmaceuticals)
Krypton is an inert gas which is not metabolized and in the concentrations applied Krypton (81mKr) shows no pharmacodynamic effects.
5.2 Pharmacokinetic properties
Krypton (81mKr) is an inert gas with a short biological half-life. Due to its rapid decay the effective half-time of lung elimination is equal to the physical half-life of 13 seconds. Peripheral Krypton (81mKr)-activity is exhaled after the first passage.
5.3 Preclinical safety data
No data available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
PTFE (polytetrafluoroethylene) membrane with immobilized poly(styrenedivinylbenzene) cation exchange resin with sulphonic acid functional groups.
6.2 Incompatibilities
None known.
6.3 Shelf life
The shelf life of the product is 20 hours after activity reference date. The expiry date is stated on the generator label.
6.4 Special precautions for storage
Do not store the generator at temperatures above 25°C. Use a lead shielding. Storage should be in accordance with the national regulations for radioactive materials.
6.5 Nature and contents of container
The radionuclide generator contains the mother-radionuclide 81Rb immobilized on a membrane. The daughter-radionuclide 81mKr is eluted by passing environmental air over the membrane. The produced gas from the generator contains therefore the radionuclide 81mKr mixed with environmental air.
The generator containing 81mKr is placed in a lexan housing and then in a shielding. The shielding is fixed within a synthetic housing.
6.6 Special precautions for disposal
Waste must be disposed of in accordance with National Regulations for radioactive material.
7 MARKETING AUTHORISATION HOLDER
Curium Netherlands B.V.
Westerduinweg 3
1755 LE Petten
Netherlands
8 MARKETING AUTHORISATION NUMBER(S)
PL 12288/0006
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
07/08/2008
10 DATE OF REVISION OF THE TEXT
30/06/2023
11 DOSIMETRY
Data from ICRP publication 53 (Vol.18; No 1-4, 1987) "radiation dose to patients from radiopharmaceuticals".
Absorbed dose per unit activity administered (mGy/MBq) ICRP 53.
Organ Adult 15 Years 10 Years 5 Years 1 Year
Adrenals 3.4E-06 5.7E-06 8.3E-06 1.3E-05 2.1E-05 Bladder wall 6.8E-08 7.6E-08 2.0E-07 4.7E-07 1.2E-06 Bone surface 1.7E-06 2.2E-06 3.2E-06 4.8E-06 9.3E-06 Breast 4.6E-06 4.6E-06 8.9E-06 1.3E-05 1.8E-05 GI-tract:
Stomach wall 2.5E-06 3.2E-06 4.4E-06 6.7E-06 1.1E-05 Small intestine 2.7E-07 4.7E-07 8.6E-07 1.6E-06 3.4E-06 ULI wall 3.2E-07 5.5E-07 1.2E-06 1.9E-06 3.5E-06 LLI wall 1.4E-07 1.5E-07 3.0E-07 8.0E-07 2.0E-06
Kidneys 1.2E-06 1.9E-06 2.9E-06 4.5E-06 8.4E-06 Liver 3.4E-06 4.8E-06 6.6E-06 9.5E-06 1.6E-05 Lungs 2.1E-04 3.1E-04 4.4E-04 6.8E-04 1.3E-03 Ovaries 1.7E-07 1.7E-07 4.1E-07 8.0E-07 1.9E-06 Pancreas 3.5E-06 4.4E-06 6.4E-06 9.8E-06 1.8E-05
Red marrow 2.1E-06 3.3E-06 4.2E-06 5.3E-06 8.2E-06 Spleen 3.1E-06 4.1E-06 6.0E-06 9.2E-06 1.6E-05 Testes 1.7E-08 2.3E-08 7.4E-08 1.3E-08 5.6E-07 Thyroid 1.2E-06 2.1E-06 3.7E-06 6.0E-06 1.1E-05 Uterus 1.3E-07 1.8E-07 3.5E-07 7.2E-07 1.8E-06
Other tissue 1.8E-06 2.3E-06 3.2E-06 4.7E-06 8.5E-06
Effective dose equivalent (mSv/MBq)
2.7E-05 4.0E-05 5.7E-05 8.8E-05 1.7E-04
For this product the effective doses equivalent resulting from an administered activity of 3000-9000 MBq, (range of actual exposure) expected activities in adults, is 0.08-0.24 mSv.
Due to the difference in half-lives the amount of 81Kr per 37 MBq 81mKr is about 2 nCi (2 µBq/MBq). Thus the contribution of 81Kr to the total radiation burden of the patient is negligible.
12 INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS
Preparation for elution
1 Remove the Krypton (81mKr) generator from the transport packing. 2 Remove the stopper from the bottom and store it in the special cut-away in the transport packing.
3 Place the generator in the ventilation device.
4 Close the cover of the Krypton ventilation device. 5 Take the Krypton supply cable from the ventilation tubing set and connect it to the Krypton ventilation device.
6 Connect the other side of the tubing set to the face mask. 7 Put the plug into a socket.
8 Adjust flow rate to maximum volume.
Administration
1 Position the patient in front of the gamma camera (equipped with a
99mTc collimator).
2 Put the face mask on the face of the patient; make sure there is no leakage.
3 Switch on power manually or by remote control. 4 Start accumulation of counts and continue until the required number is reached.
5 Switch power off.
Handling of the expired generator
1 Replace the stop that was removed earlier.
2 Store the generator in a suitable place for decay until a level of activity acceptable for return transport is reached. 3 Prepare the generator for return transport following the return procedure.
NB: IN CASE OF PROBLEMS OR OTHER ISSUES PLEASE CONSULT
YOUR LOCAL REPRESENTATIVE.
The administration of radiopharmaceuticals 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.