4.2. Posology and method of administration
The radioactivity available at time of calibration is comprised between 0.1 GBq and 8.0 GBq per vial. In oncology, the radioactivity usually recommended for adults is 4 MBq/kg of body mass administered by direct slow intravenous injection over approximately one minute. One half of this activity may be administered for neurological indications not requiring whole body images. Only few clinical data are available for patients aged under 18 years concerning safety and diagnostic effi cacy of the product, except for the detection of insulinoma in infants and children. Therefore, the use in oncologic paediatrics has to be carefully weighted. In infants, the same ponderal activity (4 MBq/kg of body mass) has been proposed as in adults.
IASOdopa must be diluted with sterile sodium bicarbonate solution 84 mg/mL prior to injection. For instructions for preparation, see section 12.
Image acquisition Neurology
- dynamic acquisition of PET images of the brain during 90 to 120 minutes right after injection
- or one static PET acquisition starting 90 minutes after the injection. Oncology To detect foci in the liver, pancreas or brain area, early ìstaticî images can be acquired starting 5 minutes after injection, or a ìdynamicî acquisition starting right after the injection during 10 minutes.
- brain tumours: ìstaticî acquisition 10 to 30 minutes after injection.
- Whole-body: images are usually acquired 60 minutes after injection
- Hypersensitivity to the active substance or to any of the excipients
4.4. Special warnings and precautions
for use For all patients, the radiation exposure must be justifi able by the expected diagnostic achieved with the lowest possible radiation dose. It should be taken into consideration that the effective dose per MBq is higher in children than in adults. 6-fl uoro-(18F)-L-dopa PET is unable to discriminate between Parkinsonës disease, multiple system atrophy and progressive supranuclear palsy.
Preparation of the patient IASOdopa should be given to subjects fasting for a minimum of 4 hours without limiting water intake.In neurological indications, it is recommended to suspend any antiparkinsonian treatment at least 12 hours before the exam. In order to obtain good quality images and avoid irradiation of the bladder, patients should be asked to drink fl uids and empty their bladder before image acquisition and frequently after the exam.The administration of 100 to 200 mg of carbidopa one to one and a half hours before the injection of 6-fl uoro-(18F)-L-dopa is recognized for neurological indications but less frequent for oncological indications. The injection must be slow and strictly intravenous in order to avoid irradiation as a result of local extravasation.
General precautions It is recommended to avoid any close contact between the patient and young children during the initial 12 hours following the injection. Radiopharmaceutical products should only be received, handled and administered by staff authorised by the competent authorities. The reception, storage, handling, transfer and disposal of these products are subject to appropriate authorisations and regulations issued by the competent authorities. Radiopharmaceuticals must be prepared in such a way as to meet standards governing both radioprotection and pharmaceutical quality. Appropriate asepsis procedures must be followed in order to meet the requirements set out in pharmaceutical Good Manufacturing Practice. The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting and saliva. Radiation protection precautions in accordance with national regulations must therefore be taken.
4.5. Interaction with other medicinal products and other forms of interaction Carbidopa:
prior to 6-fl uoro-(18F)-L-dopa administration, use of carbidopa may increase 6-fl uoro-(18F)-L-dopa bioavailability to the brain by inhibiting peripheral decarboxylase activity and restricting peripheral 6-fl uoro-(18F)-L-dopa metabolism with 3-O-methyl-6-fl uoro-(18F)-L-dopa formation. Haloperidol: increased intracerebral dopamine turnover caused by haloperidol may result in increased accumulation of 6-fl uoro-(18F)-L-dopa. Monoamine oxidase (MAO) inhibitors: concurrent use with MAO inhibitors may result in increased accumulation of 6-fl uoro- (18F)-L-dopa in the brain. Reserpine: reserpine-induced depletion of the contents of intraneuronal vesicles may prevent retention of 6-fl uoro-(18F)- L-dopa in the brain.
4.6. Pregnancy and lactation
IASOdopa is contraindicated in pregnancy. 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. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the required clinical information. Alternative methods not involving ionising radiation should be considered. No data are available concerning the use of this product during pregnancy. No studies of reproductive function have been performed in animals. Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Administration of IASOdopa at an activity of 280 MBq results in an absorbed dose to the uterus of 7,8 mGy.
Lactation When administration during lactation is unavoidable, breast milk may be drawn off before injection and stored for subsequent use. Breast feeding should be suspended for at least 12 hours and any milk produced during this period should be discarded. Moreover, for radioprotection reasons, it is recommended to avoid any close contact between the mother and young children during the initial 12 hours following injection.
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.
4.8. Undesirable effects
No serious adverse effects have been observed to date. Pain at injection has been reported in rare cases which resolved
within minutes without corrective measures. Given the small quantity of substance injected the risk lies mainly in exposure to radiations. Exposure to ionising radiation can lead to cancer or development of hereditary defects. Experience has shown that the frequency of such adverse events associated with diagnostic procedures involving nuclear medicine is very low as a result of the low levels of radioactivity employed. After administration of the maximum recommended activity of 6-fl uoro- (18F)-L-dopa for a 70 kg adult, the effi cient dose is approximately 7 mSv.
If an overdose of 6-fl uoro-(18F)-L-dopa is administered, the dose delivered to the patient must be reduced by increasing elimination of the radiopharmaceutical as far as possible through forced diuresis with frequent voiding.