ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1

2 1. NAME OF THE MEDICINAL PRODUCT DaTSCAN 74 MBq/ml solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Ioflupane ( 123 I) 74 MBq/ml at reference time ( μg/ml of ioflupane). Each vial contains 185 MBq ioflupane ( 123 I) (specific activity range x Bq/mmol) at reference time. 3. PHARMACEUTICAL FORM Solution for injection. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications This medicinal product is for diagnostic use only. DaTSCAN is indicated for detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain Parkinsonian Syndromes, 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. 4.2 Posology and method of administration DaTSCAN should only be used in patients referred by physicians experienced in the management of movement disorders. Radiopharmaceutical agents should only be used by qualified personnel with the appropriate government authorisation for the use and manipulation of radionuclides within a designated clinical setting. DaTSCAN is a 5% (v/v) ethanolic solution for intravenous injection and should be used without dilution. Clinical efficacy has been demonstrated across the range MBq. Do not exceed 185 MBq and do not use when the activity is below 110 MBq. In the event of overdosage, refer to section 4.9. 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 1-4 hours prior to injection and again hours post-injection of DaTSCAN. SPECT imaging should take place between three and six hours post-injection. Images should be acquired using a gamma camera fitted with a high-resolution collimator and calibrated using the 159keV photopeak and a ± 10% energy window. Angular sampling 2

3 should preferably be not less than 120 views over 360 degrees. For parallel hole collimators the radius of rotation should be consistent and set as small as possible (typically cm). Matrix size and zoom factors should be selected to give a pixel size of 5-7 mm. A minimum of 500k counts should be collected for optimal images. Normal images are characterised by two symmetrical crescent-shaped areas of equal intensity. Abnormal images are either asymmetric or symmetric with unequal intensity and/or loss of crescent. DaTSCAN is not recommended for use in children or adolescents, as data are not available for these populations. 4.3 Contraindications DaTSCAN is contra-indicated in pregnancy and in patients with hypersensitivity to iodide or to any of the excipients. 4.4 Special warnings and special precautions for use 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. 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. 4.5 Interaction with other medicinal products and other forms of interaction No interaction studies have been carried out in humans. Ioflupane binds to the dopamine transporter. Medicines and drugs that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis. These include amphetamine, benztropine, buproprion, cocaine, mazindol, methylphenidate, phentermine and sertraline. Drugs shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, benzhexol, 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. Drugs shown in animal studies not to interfere with DaTSCAN imaging include pergolide. 4.6 Pregnancy and lactation DaTSCAN is contraindicated in pregnancy. 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 ioflupane ( 123 I) at a dose of 185 MBq results in an absorbed dose to the uterus of 3.0 mgy. A radiation dose above 0.5 mgy would be regarded as a potential risk to the foetus. 3

4 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. Before administering a radioactive medicinal product to a mother who is breast feeding, consideration should be given as to whether the investigation could be 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 secretion of activity in breast milk. It is not known whether ioflupane ( 123 I) is secreted in human milk, therefore if administration is considered necessary, formula feeding should be substituted for breast-feeding and the expressed feeds discarded. Breast-feeding can be restarted when the level in the milk will not result in radiation dose to the child greater than 1mSv. 4.7 Effects on ability to drive and use machines None known. 4.8 Undesirable effects No serious adverse effects related to DaTSCAN administration have been reported. Common side effects are headache, vertigo and increased appetite. Formication is an uncommon side effect. 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 radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic 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 events will occur with negligible frequency because of the low radiation dose incurred. 4.9 Overdose In cases of overdosage of radioactivity, frequent micturition and defaecation should be encouraged in order to minimise radiation dosage to the patient. Care should be taken to avoid contamination from the radioactivity eliminated by the patient using such methods. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Diagnostic radiopharmaceutical for central nervous system imaging, ATC code: V09A B 03. Due to the low quantities of ioflupane injected, pharmacological effects are not expected following intravenous administration of DaTSCAN at the recommended dosage. 4

5 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 ( 123 I) can be used as a surrogate marker to examine the integrity of the dopaminergic nigrostriatal neurons. Ioflupane also binds to the serotonin transporter on 5-HT neurons but with lower (approximately 10-fold) binding affinity. There is no experience in types of tremor other than essential tremor. 5.2 Pharmacokinetic properties Ioflupane ( 123 I) is cleared rapidly from the blood after intravenous injection; only 5% of the administered activity remains in whole blood at 5 minutes post-injection. Uptake in the brain is rapid, reaching about 7% of injected activity at 10 minutes post-injection and decreasing to 3% after 5 hours. About 30% of the whole brain activity is attributed to striatal uptake. At 48 hours post-injection, approximately 60% of the injected radioactivity is excreted in the urine, with faecal excretion calculated at approximately 14%. 5.3 Preclinical safety data Acute toxicity studies employing ioflupane at dosage levels of 0.06 mg/kg, in excess of 10,000 times the maximum human (70 kg) single dose on a bodyweight basis, failed to reveal any mortality or signs of systemic toxicity in rats or rabbits. In 14 day repeat dose studies no evidence of toxicity was observed in rats or rabbits following daily doses of 0.6 mg/kg ioflupane, more than 100,000 times the maximum human (70 kg) single dose on a bodyweight basis. Behavioural effects due to pharmacological activity were observed in these studies. Studies on reproductive toxicity have not been conducted. Ioflupane showed no evidence of mutagenic potential in in vitro or in vivo mutagenicity studies. Studies to assess the carcinogenic potential of ioflupane have not been performed. 5.4 Radiation dosimetry data Iodine-123 has a physical half-life of 13.2 hours. It decays emitting gamma radiation with a predominant energy of 159 kev and X-rays of 27 kev. The estimated absorbed radiation doses to an average adult patient (70 kg) from intravenous injection of ioflupane ( 123 I) are listed below. The values are calculated assuming urinary bladder emptying at 4.8-hour intervals and appropriate thyroid blocking (Iodine-123 is a known Auger electron emitter). Frequent bladder emptying should be encouraged after dosing to minimise radiation exposure. 5

6 Target Organ Adrenals Brain Breasts Gallbladder wall Lower large intestine wall Small intestine Stomach Upper large intestine wall Heart wall Kidneys Liver Lungs Muscle Ovaries Pancreas Bone marrow Bone surfaces Skin Spleen Testes Thymus Thyroid Urinary bladder wall Uterus Total body Effective Dose Absorbed radiation dose μgy/mbq μsv/mbq 6

7 The effective dose (E) resulting from administration of a 185 MBq dose 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. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Acetic acid, sodium acetate, ethanol, water for injections. 6.2 Incompatibilities None known. 6.3 Shelf-life 7 hours from the activity reference time stated on the label (31 hours from the end of manufacture). 6.4 Special precautions for storage Do not store above 25 o C. Do not freeze. 6.5 Nature and contents of container The product is supplied in a single colourless 10 ml glass vial sealed with a rubber closure and metal overseal. The vial contains 185 MBq at reference in 2.5 ml of solution. 6.6 Instructions for use and handling, and disposal 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 Nycomed Amersham plc Little Chalfont Bucks HP7 9NA United Kingdom 8. NUMBER(S) IN THE COMMUNITY REGISTER OF MEDICINAL PRODUCTS 7

8 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10. DATE OF REVISION OF THE TEXT 8

9 ANNEX II A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OF THE MARKETING AUTHORISATION 9

10 A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer responsible for batch release Cygne B V, Den Dolech 2, Eindhoven, NL 5612 AZ, The Netherlands Manufacturing Authorisation issued 22 April 1992 by The State Secretary of Welfare, Health and Cultural Affairs, The Netherlands. B. CONDITIONS OF THE MARKETING AUTHORISATION CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product Characteristics, Section 4.2). 10

11 ANNEX III LABELLING AND PACKAGE LEAFLET 11

12 A. LABELLING 12

13 OUTER PACKAGING DaTSCAN 74 MBq/ml solution for injection Ioflupane ( 123 I) 74 MBq/ml at activity reference time. Ioflupane ( μg/ml). 5% ethanol, acetic acid, sodium acetate, water for injections. 2.5 ml Solution for injection Intravenous use. Store out of reach of children. Exp.: 7 h post-ref. Ref.: 185 MBq/2.5 ml at 1200 CET on dd/mm/yy Do not store above 25 C. Do not freeze. Handling and disposal see package leaflet. Nycomed Amersham plc Little Chalfont HP7 9NA UK EU/0/00/000 Lot: Medicinal product subject to medical prescription. 13

14 IMMEDIATE (PRIMARY) CONTAINER DaTSCAN 74 MBq/ml solution for injection Intravenous use Exp.: 7 h post-ref. Ref.: 185 MBq/2.5 ml at 1200 CET on dd/mm/yy. Lot: <XXXXXXX> 2.5 ml Cygne B V, Den Dolech 2, Eindhoven, NL 5612 AZ, The Netherlands 14

15 B. PACKAGE LEAFLET 15

16 PACKAGE LEAFLET (For medicinal products available only on prescription) Please read this leaflet carefully. It tells you about your medicine - If you have any questions or are unsure about anything, please ask your doctor. - Keep this leaflet. You may need to read it again. In this leaflet: 1. What is DaTSCAN and what is it used for? 2. Before you receive DaTSCAN 3. How is DaTSCAN used? 4. Will DaTSCAN have any side effects? 5. Storing DaTSCAN DaTSCAN 74 MBq/ml solution for injection Ioflupane ( 123 I) - The active substance is ioflupane ( 123 I). - The other ingredients are acetic acid, sodium acetate, ethanol and water for injections. DaTSCAN is marketed by: Nycomed Amersham plc Little Chalfont Bucks HP7 9NA United Kingdom DaTSCAN is manufactured by: Cygne bv Den Dolech 2 NL-5612 AZ, Eindhoven The Netherlands 1. WHAT IS DaTSCAN AND WHAT IS IT USED FOR? What is DaTSCAN? Ioflupane ( 123 I) is a radiopharmaceutical product used for diagnostic purposes. DaTSCAN is supplied as a single vial containing 185 MBq (Megabecquerel the unit in which radioactivity is measured) of the active substance ioflupane ( 123 I) in 2.5 ml of a sterile solution for intravenous injection. DaTSCAN also contains acetic acid, sodium acetate, ethanol and water for injections. A diagnostic radiopharmaceutical is a product which, when injected, temporarily collects in a specific organ or area of the body. Because it contains a small amount of radioactivity it can be detected from outside the body using special cameras and a picture, known as a scan, can be taken. This scan will show exactly the distribution of the radioactivity within the organ and the body. This can give the doctor valuable information about the structure and function of that organ. What is DaTSCAN used for? 16

17 When DaTSCAN is injected into you, it is carried around the body in the blood and collects in a small area of your brain. Parkinsonism is known to be associated with alterations in the area of the brain where DaTSCAN collects. A scan will give your doctor information about any changes in this area of your brain. Your doctor may feel that the information gained from a scan would be helpful in investigating your condition and deciding on possible treatment. This medicinal product is for diagnostic use only. 2. BEFORE YOU RECEIVE DaTSCAN Do not use DaTSCAN: If you are pregnant If you are hypersensitive (allergic) to iodide or any of the other ingredients of DaTSCAN. Special precautions before you take DaTSCAN DaTSCAN is not recommended for use in children or adolescents, and in patients with moderate to severe renal or hepatic impairment as data are not available for these populations. Before you receive DaTSCAN, your doctor will ask you to take some iodine-rich tablets or liquid, which will prevent the accumulation of radioactivity in your thyroid gland. It is important that you follow your doctor s instructions carefully. Use by pregnant or breast-feeding women You should tell your doctor if there is any possibility that you are pregnant, or if you are breast-feeding. Your doctor may delay the investigation if you are breast-feeding, or ask you to stop breast-feeding and discard the milk until the radioactivity is no longer in your body. It is not known whether ioflupane ( 123 I) is secreted in human milk, therefore if administration is considered necessary, formula feeding should be substituted for breastfeeding. Breast-feeding can be restarted when the level in the milk will not result in a radiation dose to the child greater than 1mSv. Driving and using machines: DaTSCAN is not expected to affect your ability to drive or to operate machinery. Important information about some of the ingredients of DaTSCAN: The use of DaTSCAN does involve exposure to small amounts of radioactivity. Although this exposure is less than in some types of X-ray investigation, your doctor will always consider the possible risks and benefits. IN CASE OF DOUBT IT IS ESSENTIAL TO CONSULT YOUR DOCTOR BEFORE YOU RECEIVE THIS PRODUCT. Taking other medicines: Some medicines and substances such as amphetamine, cocaine, buproprion, benztropine, mazindol, sertraline methylphenidate and phentermine may interfere with DaTSCAN 17

18 diagnosis. Other medication used to treat Parkinson s disease, e.g. levodopa, will not interfere with imaging and can therefore be continued. You may be asked to stop taking some medicines for a short time before you receive DaTSCAN if your doctor thinks that these may interfere with the quality of the picture obtained. IN ORDER TO AVOID POSSIBLE INTERACTIONS WITH OTHER MEDICINAL PRODUCTS YOU SHOULD TELL YOUR DOCTOR IF YOU ARE TAKING ANY OTHER MEDICINE, EITHER PRESCRIBED OR BOUGHT WITHOUT PRESCRIPTION. 3. HOW IS DaTSCAN USED? The clinical efficacy of DaTSCAN has been demonstrated across the range MBq. The dose administered should not exceed 185 MBq. DaTSCAN is administered as an injection into a vein. A single injection is sufficient to give your doctor the information he needs. The imaging should take place between 3 and 6 hours after injection of DaTSCAN. What will happen if you receive an overdose? Since DaTSCAN is administered by a doctor under strictly controlled conditions, any overdose is unlikely. Your doctor will recommend that you drink plenty of fluids to speed removal of the radiopharmaceutical from your body. You should take special care to avoid contamination from the radioactivity eliminated using such methods. This is standard practice in the use of a diagnostic radiopharmaceutical. Any ioflupane ( 123 I) which remains in your body will naturally lose its radioactivity. Because there are strict laws covering the use, handling and disposal of radioactivity, DaTSCAN will always be used in a hospital or a similar setting. It will only be handled and administered by people who are trained and qualified in the safe handling of radioactive material. They should advise you on any precautions you need to take. 4. WILL DaTSCAN HAVE ANY SIDE-EFFECTS? Like all medicines, DaTSCAN can have side-effects. Common side-effects are headache, vertigo (dizziness) and increased appetite. A brief irritating sensation similar to ants crawling over your skin (formication) is an uncommon side effect. The amount of radioactivity in the body as a result of the injection of DaTSCAN is very small and will be passed out of the body in a few days without need for special precautions. If you have any concerns, consult your doctor. 18

19 IT IS IMPORTANT THAT YOU TELL YOUR DOCTOR IF YOU FEEL ANY ILL- EFFECTS, WHETHER OR NOT THEY ARE OF A TYPE MENTIONED IN THIS LEAFLET. 5. STORING DaTSCAN Store out of reach of children. Do not store above 25 C. Do not freeze. The product label includes the appropriate storage conditions and the expiry date for the batch of product. Hospital personnel will ensure that the product is stored correctly and not administered to you after the expiry date. This leaflet was prepared on {date} Further information The above information is a summary. For further information on DaTSCAN, ask your doctor. 19

20 For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder. België/Belgique/Belgien Nycomed Amersham n.v. Chaussée de Gand, 615 Gentsesteenweg B-1080 Brussel/Bruxelle Tél: Danmark Nycomed Amersham A/S Slotsmarken 15 DK 2970 Hørsholm Tlf: Deutschland Amersham Buchler GmbH & Co KG Gieselweg 1 D Braunschweig Tel: Ελλάδα Nycomed HELLAS S.A. Λεωφ. Κηφισίας 196 GR ΧΑΛΑΝΔΡΙ, ΑΘΗΝΑ Τηλ: España Nycomed Amersham, S.A. Ronda de Poniente, 12 Euronova E Tres Cantos Madrid Tel: France Nycomed Amersham SA Centre d Affaires et d Activités Tolbiac - Massena 25,quai Panhard et Levassor F Paris Tél: Ireland Nycomed Amersham plc Little Chalfont Buckinghamshire HP7 9NA Tel: Luxembourg/Luxemburg Nycomed Amersham n.v. Chaussée de Gand, 615 Gentsesteenweg L-1080 Brussel/Bruxelle Tél: Nederland Amersham Cygne Den Dolech 2 NL-5612 AZ Eindhoven Tel: Österreich Nycomed Austria GmbH St. Peter Strasse 25 A-4021 LINZ Tel: Portugal Satis Unipessoal Lda. Estrada da Alagoa, lote A-27 1 o C/D Apartado 169 P Carcavelos Tel: Suomi/Finland OY Nycomed AB Vallikallionkatu 1 POB 29 FIN Espoo/Esbo Puh/Tln: Sverige Nycomed Amersham AB Tryffelslingen 14 PO Box 1215 S Lidingö Tln: United Kingdom Nycomed Amersham plc Little Chalfont Buckinghamshire HP7 9NA Tel: Italia Nycomed Amersham Sorin S.r.l. Via Crescentino I Saluggia (VC) Tel: