STRIASCAN 74 MBQ/ml injectible solution medication leaflet

Striascan 74 MBq/mL solution for injection

Each mL of solution contains 74 MBq of ioflupane (123I) at reference time (0.07 to 0.13 µg/mL ofioflupane).

Each 2.5 mL single dose vial contains 185 MBq ioflupane (123I) (specific activity range 2.5 to4.5 x 1014 Bq/mmol) at reference time.

Each 5 mL single dose vial contains 370 MBq ioflupane (123I) (specific activity range 2.5 to4.5 x 1014 Bq/mmol) at reference time.

Iodine-123 has a physical half-life of 13.2 hours. It decays emitting gamma radiation with a predominantenergy of 159 keV and X-rays of 27 keV.

For the full list of excipients see section 6.1.

Solution for injection.

Clear colourless solution.

This medicinal product is for diagnostic use only.

Striascan 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 earlysymptoms, in order to help differentiate essential tremor from parkinsonian syndromes related toidiopathic Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy.

Striascan is unable to discriminate between Parkinson's disease, multiple system atrophy andprogressive supranuclear palsy.

* In adult patients, to help differentiate probable dementia with Lewy bodies from Alzheimer’sd i s e a s e . Striascan is unable to discriminate between dementia with Lewy bodies and

Parkinson’s disease dementia.

Striascan should only be used in adult patients referred by physicians experienced in the management ofmovement disorders and/or dementia.

This medical product is for use in hospitals or in designated nuclear medicine facilities only.

Clinical efficacy has been demonstrated across the range 110 to 185 MBq. Do not exceed 185 MBq anddo not use when the activity is below 110 MBq.

Patients must undergo appropriate thyroid blocking treatment prior to injection to minimise thyroiduptake of radioactive iodine, for example by oral administration of approximately 120 mg potassiumiodide 1 to 4 hours prior to injection of Striascan.

Formal studies have not been carried out in patients with significant renal or hepatic impairment. No dataare available (see section 4.4).

Careful consideration of the activity to be administered is required since an increased radiation exposureis possible in these patients.

The safety and efficacy of Striascan in children and adolescents aged 0 to 18 years has not beenestablished. No data are available.

Striascan is for intravenous use.

For patient preparation, see section 4.4.

Striascan should be used without dilution. To minimise the potential for pain at the injection site duringadministration, a slow intravenous injection (not less than 15 to 20 seconds) via an arm vein isrecommended.

Image acquisition

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 calibratedusing the 159 keV photopeak and a ± 10% energy window. Angular sampling should preferably be notless than 120 views over 360 degrees.

For high resolution collimators the radius of rotation should be consistent and set as small as possible(typically 11-15 cm). Experimental studies with a striatal phantom, suggest that optimal images areobtained with matrix size and zoom factors selected to give a pixel size of 3.5-4.5 mm for those systemscurrently in use. A minimum of 500 k counts should be collected for optimal images.

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy (see section 4.6).

Potential for hypersensitivity or anaphylactic reactions

If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must bediscontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action inemergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilatormust be immediately available.

Individual benefit/risk justification

For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administeredshould in every case be as low as reasonably achievable to obtain the required diagnostic information.

Renal impairment/Hepatic impairment

Formal studies have not been carried out in patients with significant renal or hepatic impairment. In theabsence of data, Striascan is not recommended in cases of moderate to severe renal or hepaticimpairment.

Careful consideration of the benefit risk ratio in these patients is required since an increased radiationexposure is possible.

Patient preparation

The patient should be well hydrated before and after the examination and urged to void as often aspossible during the first 48 hours after the procedure in order to minimise radiation exposure.

Interpretation of Striascan Images

Striascan images are interpreted visually, based upon the appearance of the striata.

Optimum presentation of the reconstructed images for visual interpretation is transaxial slices parallel tothe anterior commissure-posterior commissure (AC-PC) line. Determination of whether an image isnormal or abnormal is made by assessing the extent (as indicated by shape) and intensity (in relation tothe background) of the striatal signal.

Normal images are characterised by two symmetrical crescent-shaped areas of equal intensity. Abnormalimages are either asymmetric or symmetric with unequal or reduced intensity and/or loss of crescent.

As an adjunct, visual interpretation may be assisted by semi-quantitative assessment using CE-markedsoftware, where Striascan uptake in the striatum is compared with uptake in a reference region and ratiosare compared against an age adjusted healthy subjects’ database. The evaluation of ratios, such as theleft/right striatum Striascan uptake (symmetry) or caudate/putamen uptake, may further help with theimage assessment.

The following precautions should be taken when using semi-quantitative methods:

* Semi-quantification should only be used an adjunct to visual assessment

* Only CE marked software should be used

* Users should be trained in the use of CE marked software by the manufacturer and follow EANMpractice guidelines for image acquisition, reconstruction and assessment

* Readers should interpret the scan visually and then perform the semi-quantitative analysisaccording to manufacturer’s instructions including quality checks for the quantitation processo ROI /VOI techniques should be used to compare uptake in the striatum with uptake in areference regiono Comparison against an age adjusted healthy subjects database is recommended to accountfor age-expected decrease in striatal bindingo The reconstruction and filter settings (including attenuation correction) used can affectthe semi-quantitative values. The reconstruction and filter settings recommended by themanufacturer of the CE marked software should be followed and should match thoseused for semi-quantification of the healthy subjects database.

o The intensity of the striatal signal as measured by SBR (striatal binding ratio) andasymmetry and caudate to putamen ratio provide objective numerical valuescorresponding to the visual assessment parameters and can be helpful in difficult to readcaseso If the semi-quantitative values are inconsistent with the visual interpretation, the scanshould be evaluated for appropriate placement of the ROIs /VOIs, correct imageorientation and appropriate parameters for image acquisition and attenuation correctionshould be verified. Some software packages can support these processes to reduceoperator-dependent variabilityo Final assessment should always consider both visual appearance and semi-quantitativeresults

Specific warnings

This medicinal product contains up to 197 mg of alcohol (ethanol) in each dose which is equivalent to39.5 mg/mL (5% by volume). The amount in 5 mL of this medicinal product is equivalent to 5 mL beer or2 mL wine. The small amount of alcohol in this medicinal product will not have any noticeable effects.

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially‘sodium-free’.

Precautions with respect to environmental hazard see section 6.6.

No interaction studies have been performed in humans.

Ioflupane binds to the dopamine transporter. Active substances that bind to the dopamine transporter withhigh affinity may therefore interfere with Striascan diagnosis. These include:

- amfetamine,

- bupropion,

- cocaine,

- codeine,

- dexamfetamine,

- methylphenidate,

- modafinil,

- phentermine,

Selective serotonin reuptake inhibitors, such as sertraline, may increase or decrease ioflupane binding tothe dopamine transporter.

Active substances shown during clinical trials not to interfere with Striascan imaging include:

- amantadine,

- trihexyphenidyl,

- budipine,

- levodopa,

- metoprolol,

- primidone,

- propranolol and

- selegiline.

Dopamine agonists and antagonists acting on the postsynaptic dopamine receptors are not expected tointerfere with Striascan imaging and can therefore be continued if desired. Medicinal products shown inanimal studies not to interfere with Striascan imaging include pergolide.

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it isimportant to determine whether or not she is pregnant. Any woman who has missed a period should beassumed to be pregnant until proven otherwise.

If in doubt about her potential pregnancy (if the woman has missed a period, if the period is veryirregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered tothe patient.

Animal reproductive toxicity studies have not been performed with this product.

Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus.

Administration of 185 MBq of ioflupane (123I) results in an absorbed dose to the uterus of 2.6 mGy.

Striascan is contraindicated in pregnancy (see section 4.3).

It is not known whether ioflupane (123I) is excreted in human milk. Before administeringradiopharmaceuticals to a mother who is breast-feeding, consideration should be given to the possibilityof delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what isthe most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breastmilk.

If administration is considered necessary, breast-feeding should be interrupted for 3 days and substitutedby formula feeding. During this time, breast milk should be expressed at regular intervals and theexpressed feeds should be discarded.

No fertility studies have been performed. No data are available.

Striascan has no known influence on the ability to drive and use machines.

The following undesirable effects are recognised for ioflupane (123I).

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)

Not known (cannot be estimated from the available data)

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

MedDRA Body system Adverse reaction Frequency

SOCs Preferred term

Immune system disorders Hypersensitivity Not known

Metabolism and nutrition Appetite increased Uncommondisorders

Nervous system disorders Headache Common

Dizziness, formication Uncommon(paraesthesia), dysgeusia

Ear and labyrinth disorders Vertigo Uncommon

Vascular disorders Blood pressure decreased Not known

Respiratory, thoracic and Dyspnea Not knownmediastinal disorders

Gastrointestinal disorders Nausea, dry mouth Uncommon

Vomiting Not known

Skin and subcutaneous tissue Erythema, pruritus, rash, Not knowndisorders urticaria, hyperhidrosis

General disorders and Injection site pain (intense pain Uncommonadministration site conditions or burning sensation followingadministration into small veins)

Feeling hot Not known

Exposure to ionising radiation is linked with cancer induction and a potential for development ofhereditary defects. As the effective dose is 4.6 mSv when the maximal recommended activity of 185 MBqis administered these adverse events are expected to occur with a low probability.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allowscontinued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals areasked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the event of administration of a radiation overdose, frequent micturition and defaecation should beencouraged in order to minimise radiation dose to the patient. Care should be taken to avoidcontamination from the radioactivity eliminated by the patient using such methods.

Pharmacotherapeutic group: Diagnostic radiopharmaceutical central nervous system,

ATC code: V09AB03.

At the chemical concentrations used for diagnostic examinations, Striascan does not appear to have anypharmacodynamic activity.

Ioflupane is a cocaine analogue. Studies in animals have shown that ioflupane binds with high affinity tothe presynaptic dopamine transporter and so radiolabelled ioflupane (123I) can be used as a surrogatemarker to examine the integrity of the dopaminergic nigrostriatal neurons. Ioflupane also binds to theserotonin 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.

Clinical studies in patients with dementia with Lewy bodies.

In a 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 ioflupane (123I) images were compared tothe clinical diagnosis as determined by physicians experienced in the management and diagnosis ofdementias. Clinical categorisation into the respective dementia group was based on a standardised andcomprehensive clinical and neuropsychiatric evaluation. The values for the sensitivity of ioflupane (123I)in determining probable DLB from non-DLB ranged from 75.0% to 80.2% and specificity from 88.6% to91.4%. The positive predictive value ranged from 78.9% to 84.4% and the negative predictive value from86.1% to 88.7%. Analyses in which both possible and probable DLB patients were compared with non-

DLB dementia patients demonstrated values for the sensitivity of ioflupane (123I) ranging from 75.0% to80.2% and specificity from 81.3% to 83.9% when the possible DLB patients were included as non-DLBpatients. The sensitivity ranged from 60.6% to 63.4% and specificity from 88.6% to 91.4% when thepossible DLB patients were included as DLB patients.

Clinical studies demonstrating adjunctive use of semi-quantitative information for image interpretation

The reliability of using semi-quantitative information as an adjunct to visual inspection was analysed infour clinical studies where sensitivity, specificity or overall accuracy between the two methods of imageinterpretation were compared. In the four studies (total n=578), CE-marked DaTSCAN semi-quantitationsoftware was used. The differences (i.e., improvements when adding semi-quantitative information tovisual inspection) in sensitivity ranged between 0.1% and 5.5%, in specificity between 0.0% and 2.0%,and in overall accuracy between 0.0% and 12.0%.

The biggest of these four studies retrospectively assessed a total of 304 DaTSCAN exams frompreviously conducted Phase 3 or 4 studies, which included subjects with a clinical diagnosis of PS, non-

PS (mainly ET), probable DLB, and non-DLB (mainly AD). Five nuclear medicine physicians who hadlimited prior experience with DaTSCAN interpretation assessed the images in 2 readings (alone andcombined with semi-quantitative data provided by DaTQUANT 4.0 software) at least 1 month apart.

These results were compared with the subject’s 1-to 3-year follow-up diagnosis to determine diagnosticaccuracy. The improvements in sensitivity and specificity [with 95% confidence intervals] were0.1% [-6.2%,6.4%] and 2.0% [-3.0%,7.0%]. Also, the results of the combined reading were associatedwith an increase in reader confidence.

Ioflupane (123I) is cleared rapidly from the blood after intravenous injection; only 5% of the administeredactivity remains in whole blood at 5 minutes post-injection.

Organ uptake

Uptake in the brain is rapid, reaching about 7% of injected activity at 10 minutes post-injection anddecreasing 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, withfaecal excretion calculated at approximately 14%.

Non-clinical data for ioflupane reveal no special hazard for humans based on conventional studies ofsafety pharmacology, single and repeated dose toxicity and genotoxicity.

Studies on reproductive toxicity and to assess the carcinogenic potential of ioflupane have not beenperformed.

Environmental Risk Assessment (ERA)

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 wasteand 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.

Acetic acid, glacial (E 260)

Sodium acetate, trihydrate (E 262)

Ethanol, anhydrous (E 1510)

Phosphoric acid, concentrated (E 338)

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

2.5 mL vial35 hours from the end of synthesis (7 hours from the activity reference time stated on the label)5 mL vial48 hours from the end of synthesis (20 hours from the activity reference time stated on the label)

Do not store above 25°C. Do not freeze.

Store in the original lead shielding.

Storage of radiopharmaceuticals should be in accordance with national regulation on radioactivematerials.

15 mL amber glass vial sealed with a rubber closure and metal overseal.

The vial is placed into a lead container for protective shielding and packed in a metal box.

Pack size: 1 vial containing 2.5 mL or 5 mL of solution.

Not all pack sizes may be marketed.

General warning

Radiopharmaceuticals should be received, used and administered only by authorised persons indesignated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulationsand/or appropriate licences of the competent official organisation.

Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety andpharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

If at any time in the preparation of this product the integrity of this vial is compromised it should not beused.

Administration procedures should be carried out in a way to minimise risk of contamination of themedicinal product and irradiation of the operators. Adequate shielding is mandatory.

The administration of radiopharmaceuticals creates risks for other persons from external radiation orcontamination from spill of urine, vomiting etc. Radiation protection precautions in accordance withnational regulations must therefore be taken.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

CIS bio international

RN 306 - Saclay

B.P. 32

F-91192 Gif-sur-Yvette Cedex

EU/1/19/1372/001 (2.5 mL)

EU/1/19/1372/002 (5 mL)

Date of first authorisation: 25 june 2019

Date of latest renewal: 11 March 2024

The biokinetic model for ioflupane (123I) adopted by ICRP 128 ((International Commission on

Radiological Protection ,2015) assumes initial uptake of 31% of the administered activity in the liver,11% in the lungs, and 4% in the brain. The rest is assumed to be distributed uniformly in the remainingorgans and tissues. For all organs and tissues, 80% is assumed to be excreted with a biological half-timeof 58 h, and 20% with a half-time of 1.6 h. It is further assumed that 60% of the injected activity isexcreted to the urine, and 40% is excreted to the gastrointestinal tract for all organs and tissues. Activityin the liver is excreted according to the Publication 53 gallbladder model (ICRP, 1987), where 30% iseliminated via the gallbladder and the remainder passes directly into the small intestine.

The estimated absorbed radiation doses to an average adult patient (70 kg) from intravenous injection ofioflupane (123I) are listed below according to ICRP 128.

The values are calculated assuming urinary bladder emptying at 4.8-hour intervals and appropriatethyroid blocking (Iodine-123 is a known Auger electron emitter)

Organ Absorbed radiation doseμGy/MBq

Adrenals 17

Bone surfaces 15

Brain 16

Breasts 7.3

Gallbladder wall 44

Gastrointestinal tract

Stomach wall 12

Small intestine wall 26

Colon wall 59(Upper large intestine wall ) 57(Lower large intestine wall) 62

Heart wall 32

Kidneys 13

Liver 85

Lungs 42

Muscle 8.9

Oesophagus 9.4

Ovaries 18.0

Pancreas 17.0

Red marrow 9.3

Salivary glands 41.0

Skin 5.2

Spleen 26.0

Testes 6.3

Thymus 9.4

Thyroid 6.7

Urinary bladder wall 35.0

Uterus 14.0

Remaining organs 10.0

Effective Dose 25.0 μSv/MBq

The effective dose (E) resulting from administration of 185 MBq of Striascan injection is 4.6 mSv (per70 kg individual). The above data are valid in normal pharmacokinetic behaviour. When renal or hepaticfunction is impaired, the effective dose and the radiation dose delivered to organs might be increased.

For an administered activity of 185 MBq the typical radiation dose to the target organ (brain) is 3 mGyand the typical radiation doses to the critical organs: liver and colon wall are 16 mGy and 11 mGy,respectively.

Not relevant.

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.