- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 3. PHARMACEUTICAL FORM
- 4. CLINICAL PARTICULARS
- 5. PHARMACOLOGICAL PROPERTIES
- 6. PHARMACEUTICAL PARTICULARS
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBERS
- 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
- 10. DATE OF REVISION OF THE TEXT
1.NAME OF THE MEDICINAL PRODUCT
DaTSCAN 74 MBq/ml solution for injection
2.QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of solution contains ioflupane (123I) 74 MBq at reference time (0.07 to 0.13 μg/ml of ioflupane).
Each 2.5 ml single dose vial contains 185 MBq ioflupane (123I) (specific activity range 2.5 to 4.5 x 1014 Bq/mmol) at reference time.
Each 5 ml single dose vial contains 370 MBq ioflupane (123I) (specific activity range 2.5 to 4.5 x 1014 Bq/mmol) at reference time.
Excipient(s) with known effect
This medicinal product contains 39.5 g/l ethanol.
For the full list of excipients see section 6.1.
Solution for injection.
Clear colourless solution.
This medicinal product is for diagnostic use only.
DaTSCAN is indicated for detecting loss of functional dopaminergic neuron terminals in the striatum:
•In adult patients with clinically uncertain Parkinsonian Syndromes, for example those with early symptoms, in order to help differentiate Essential Tremor from Parkinsonian Syndromes related to idiopathic Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy. DaTSCAN is unable to discriminate between Parkinson's Disease, Multiple System Atrophy and Progressive Supranuclear Palsy.
•In adult patients, to help differentiate probable dementia with Lewy bodies from Alzheimer’s disease.
DaTSCAN is unable to discriminate between dementia with Lewy bodies and Parkinson’s disease dementia.
4.2Posology and method of administration
Prior to administration appropriate resuscitation equipment should be available.
DaTSCAN should only be used in adult patients referred by physicians experienced in the management of movement disorders and/or dementia. DaTSCAN should only be used by qualified personnel with the
appropriate government authorisation for the use and manipulation of radionuclides within a designated clinical setting.
Clinical efficacy has been demonstrated across the range 111 to 185 MBq. Do not exceed 185 MBq and do not use when the activity is below 110 MBq.
Patients must undergo appropriate thyroid blocking treatment prior to injection to minimise thyroid uptake of radioactive iodine, for example by oral administration of approximately 120 mg potassium iodide 1 to 4 hours prior to injection of DaTSCAN.
Renal and hepatic impairment
Formal studies have not been carried out in patients with significant renal or hepatic impairment. No data are available (see section 4.4).
The safety and efficacy of DaTSCAN in children aged 0 to 18 years has not been established. No data are available.
Method of Administration
For intravenous use.
DaTSCAN should be used without dilution. To minimise the potential for pain at the injection site
during administration, a slow intravenous injection (not less than 15 to 20 seconds) via an arm vein is recommended.
SPECT imaging should take place between three and six hours
acquired using a gamma camera fitted with a
159 keV photopeak and a ± 10% energy window. Angular sampling should preferably be not less than 120 views over 360 degrees. For high resolution collimators the radius of rotation should be consistent and set as small as possible (typically
intensity. Abnormal images are either asymmetric or symmetric with unequal intensity and/or loss of crescent.
Hypersensitivity to the active substance or to any of the excipients listed in section 6,1.
Pregnancy (see section 4.6).
Special warnings and precautions for use
If hypersensitivity reactions occur, the administration of the medicinal product must be discontinued immediately and, if necessary, intravenous treatment initiated. Resuscitative medicinal products and equipment (e.g. endotracheal tube and ventilator) have to be readily available.
This radiopharmaceutical may be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and the appropriate licences of the local competent official organisations.
For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting dose is as low as reasonably achievable bearing in
mind the need to obtain the intended diagnostic result.
Formal studies have not been carried out in patients with significant renal or hepatic impairment. In the
absence of data, DaTSCAN is not recommended in cases of moderate to severe renal or hepatic impairment.
This medicinal product contains 39.5 g/l (5% volume) ethanol (alcohol), up to 197 mg per dose, equivalent to 5 ml beer or 2 ml wine. Harmful for those suffering from alcoholism. To be taken into account in
4.5Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed in humans.
Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis. These include amfetamine, benzatropine, buproprion, cocaine, mazindol, methylphenidate, phentermine and sertraline.
Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline. Dopamine
agonists and antagonists acting on the postsynaptic dopamine receptors are not expected to interfere with DaTSCAN imaging and can therefore be continued if desired. Medicinal products shown in animal studies not to interfere with DaTSCAN imaging include pergolide.
4.6Fertility, pregnancy and lactation
Women of childbearing potential
Where 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 pregnant until proven otherwise. Where uncertainty exists, it is important that radiation
exposure should be the minimum consistent with achieving satisfactory imaging. Alternative techniques which do not involve ionising radiation should be considered.
Animal reproductive toxicity studies have not been performed with this product. Radionuclide
procedures carried out on pregnant women also involve radiation doses to the foetus. Administration of 185 MBq of ioflupane (123I) results in an absorbed dose to the uterus of 3.0 mGy. DaTSCAN is
contraindicated in pregnancy (see section 4.3).
It is not known whether ioflupane (123I) is excreted in human milk. Before administering a radioactive medicinal product to a
the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretion of radioactivity in breast milk. If administration is considered necessary,
No fertility studies have been performed. No data are available.
4.7Effects on ability to drive and use machines
DaTSCAN has no known influence on the ability to drive and use machines.
Summary of the safety profile
No serious adverse reactions related to DaTSCAN administration have been reported.
Tabulated summary of adverse reactions
The frequencies of adverse reactions are defined as follows:
Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥
1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Immune system disorders
Not known: Hypersensitivity
Metabolism and nutrition disorders
Uncommon: Appetite increased
Nervous system disorders
Uncommon: Dizziness, formication (paraesthesia), dysgeusia
Ear and labyrinth disorders
Uncommon: Nausea, dry mouth
General disorders and administration site conditions
Uncommon: Injection site pain (intense pain following administration into small veins)
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 4.35 mSv when the maximal recommended activity of
185 MBq is administered these adverse events are expected to occur with a low probability.
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.
In cases of overdose of radioactivity, frequent micturition and defaecation should be encouraged in order to minimise radiation dose to the patient. Care should be taken to avoid contamination from the radioactivity eliminated by the patient using such methods.
Pharmacotherapeutic group: Diagnostic radiopharmaceutical central nervous system, ATC code: V09AB03.
Due to the low quantities of ioflupane injected, pharmacological effects are not expected following intravenous administration of DaTSCAN at the recommended dosage.
Mechanism of action
Ioflupane is a cocaine analogue. Studies in animals have shown that ioflupane binds with high affinity to
the presynaptic dopamine transporter and so radiolabelled ioflupane (123I) can be used as a surrogate marker to examine the integrity of the dopaminergic nigrostriatal neurons. Ioflupane also binds to the
serotonin transporter on
There is no experience in types of tremor other than essential tremor.
Clinical studies in patients with dementia with Lewy bodies
In a pivotal clinical trial including evaluation of 288 subjects with dementia with Lewy bodies (DLB) (144 subjects), Alzheimer’s disease (124 subjects), vascular dementia (9 subjects) or other (11 subjects), the results of an independent, blinded visual assessment of the DaTSCAN images were compared to the
clinical diagnosis as determined by physicians experienced in the management and diagnosis of dementias. Clinical categorisation into the respective dementia group was based on a standardised and
comprehensive clinical and neuropsychiatric evaluation. The values for the sensitivity of DaTSCAN in determining probable DLB from
from 86.1% to 88.7%. Analyses in which both possible and probable DLB patients were compared with
to 80.2% and specificity from 81.3% to 83.9% when the possible DLB patients were included as
Ioflupane (123I) is cleared rapidly from the blood after intravenous injection; only 5% of the administered activity remains in whole blood at 5 minutes
Uptake in the brain is rapid, reaching about 7% of injected activity at 10 minutes
At 48 hours
5.3Preclinical safety data
Studies on reproductive toxicity and to assess the carcinogenic potential of ioflupane have not been performed.
6.1List of excipients
Water for injections
2.5 ml vial: 7 hours from the activity reference time stated on the label. 5 ml vial: 20 hours from the activity reference time stated on the label.
6.4Special precautions for storage
Do not store above 25oC. Do not freeze.
6.5Nature and contents of container
2.5 or 5 ml solution in a single colourless 10 ml glass vial sealed with a rubber closure and metal overseal.
Pack size of 1.
Not all pack sizes may be marketed.
6.6Special precautions for disposal and other handling
Normal safety precautions for handling radioactive materials should be observed.
After use, all materials associated with the preparation and administration of radiopharmaceuticals, including any unused product and its container, should be decontaminated or treated as radioactive waste and disposed of in accordance with the conditions specified by the local competent authority. Contaminated material must be disposed of as radioactive waste via an authorised route.
7.MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Bucks HP7 9NA
8.MARKETING AUTHORISATION NUMBERS
EU/1/00/135/001 (2.5 ml)
EU/1/00/135/002 (5 ml)
9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 27 July 2000
Date of latest renewal: 28 July 2010
10.DATE OF REVISION OF THE TEXT
The estimated absorbed radiation doses to an average adult patient (70 kg) from intravenous injection of ioflupane (123I) are listed below. The values are calculated assuming urinary bladder emptying at
Absorbed radiation dose
Lower large intestine wall
Upper large intestine wall
Urinary bladder wall
The effective dose (E) resulting from administration of 185 MBq of DaTSCAN injection is 4.35 mSv (per 70 kg individual). The above data are valid in normal pharmacokinetic behaviour. When renal or
hepatic function is impaired, the effective dose and the radiation dose delivered to organs might be increased.
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
Any unused medicinal product or waste material should be disposed of in accordance with local requirements. See also section 6.6.
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu