SUMMARY OF PRODUCT CHARACTERISTICS
1 1. NAME OF THE MEDICINAL PRODUCT
Sogacin 20 MBq/mL, solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One mL contains 20 MBq of gallium (68Ga) edotreotide at the date and time of calibration.
At this time, the activity per vial is 200 MBq, corresponding to an activity at end of synthesis ranging from 200 MBq to 930 MBq per vial.
Gallium (68Ga) decays to stable zinc (68Zn) with a half-life of 68 minutes by emitting X rays with energies of 9 to 10 keV, positronic radiations with mean energies of 353 and 836 keV, followed by photonic annihilation radiations of 511 keV, and gamma radiation of 1 077 keV.
Excipients with known effect: Each mL of Sogacin contains up to 3.5 mg of sodium and a maximum of 0.074 mL of ethanol. For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Solution for injection Clear and colourless solution
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
This medicinal product is for diagnostic use only.
Sogacin binds specifically to somatostatin receptors.
Sogacin is indicated for use with positron emission tomography (PET).
Sogacin is used for imaging in patients undergoing oncologic diagnostic procedures describing functions or diseases where enhanced somatostatin receptors expression of specific organs or tissues is the diagnostic target.
The following indications have been particularly documented: - detection of the primary occult neuroendocrine tumour when a metastasis of neuroendocrine tumour has been demonstrated or when the serum concentration of a specific marker is increased, - characterisation of bronchial mass as neuroendocrine tumour when other diagnostic modalities have not been conclusive, - characterisation, initial staging, detection in case of biochemical recurrence and restaging of neuroendocrine tumours of the foregut, including in the thymus or the bronchi, - characterisation, initial staging, detection in case of biochemical recurrence and restaging of neuroendocrine tumours of the midgut, when 6-fluoro-(18F)-L-dihydroxyphenylalanine is not available or when PET with 6-fluoro-(18F)-L-dihydroxyphenylalanine is non-conclusive, - as an adjunct to anatomic imaging in pre-therapeutic evaluation of meningeoma.
Tumours which do not bear somatostatin receptors will not be visualised with Sogacin.
4.2. Posology and method of administration
Posology
2 Adults and elderly
The recommended activity for an adult weighing 70 kg is 100 to 200 MBq (the activity will be adapted to the body mass, the type of camera used, PET or PET/CT, and acquisition mode), administered by direct intravenous injection.
Patients with renal impairment Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.
Paediatric population There is limited clinical data on the safety and efficacy of this product in the under 18 year old patient. The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) for paediatric task group Dosage Card; the activity administered to children and to adolescents may be calculated by multiplying a recommended activity for an adult (for calculation purposes) by the multiples given in the table below.
A(MBq)Administered = Recommended Activity for an adult × Multiple
Weight (kg) Multiple Weight (kg) Multiple Weight (kg) Multiple 3 0.1 22 0.50 42 0.78 4 0.14 24 0.53 44 0.80 6 0.19 26 0.56 46 0.82 8 0.23 28 0.58 48 0.85 10 0.27 30 0.62 50 0.88 12 0.32 32 0.65 52-54 0.90 14 0.36 34 0.68 56-58 0.92 16 0.40 36 0.71 60-62 0.96 18 0.44 38 0.73 64-66 0.98 20 0.46 40 0.76 68 0.99
Method of administration For intravenous use. The injection of Sogacin must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts. The injection site should be selected remote from the pathological areas to be examined in priority, usually in the forearm. For multidose use
Precautions to be taken before handling or administration of the medicinal product For patient preparation, see section 4.4. The activity of Sogacin has to be measured with an activimeter immediately prior to injection.
Image acquisition Image acquisition starts between 45 and 60 minutes after injection. If required, repeated gallium (68Ga) edotreotide PET examinations can be reiterated within a short period of time.
4.3. Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Pregnancy (see section 4.6)
4.4. Special warnings and precautions for use
Individual benefit/risk justification
3 For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable in order to obtain the required diagnostic information.
Diagnostic efficacy of gallium (68Ga) edotrotide has not been demonstrated in the pretherapeutic dosimetry evaluation prior to peptide receptor radionuclide therapy targeting somatostatin receptors.
Renal impairment Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.
Paediatric population For information on the use in paediatric population, see section 4.2.
Patient preparation Administration of Sogacin does not require that the patient be fasting. In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.
Interpretation of Sogacin images PET images with Sogacin reflect the density of somatostatin receptors. The image interpretation must take into account the normal biodistribution of the radiopharmaceutical. Sogacin is constantly taken-up by the normal pituitary gland, thyroid gland, liver, spleen, kidneys and adrenals. Sogacin may also be variably taken-up by the normal posterior part of the head of the pancreas (uncinate process). Some pathological conditions (like subacute inflammation, breast cancer, lymphoma) can also show a variable uptake of Sogacin. Inversely, tumours which do not bear somatostatin receptors will not be visualised with Sogacin. In case of Cushing syndrome, a long-term exposure to endogenous hypercortisolism may down regulate somatostatin receptor expression and negatively influence the results of somatostatin receptor imaging with gallium (68Ga) edotreotide. In patients with Cushing syndrome, the normalisation of hypercortisolism should be considered before performing PET with gallium (68Ga) edotreotide. An increased uptake of gallium (68Ga) edotreotide is not specific for GEP-NET. Positive results require evaluating the possibility that another disease, characterised by high local somatostatin receptor concentrations, may be present. For example, an increase in somatostatin receptor density can also occur in the following pathological conditions: subacute inflammations (areas of lymphocyte concentrations), thyroid diseases (e.g. autonomous thyroid nodule and Hashimoto’s thyroiditis), tumours of the pituitary gland, neoplasms of the lungs (small-cell carcinoma), meningiomas, mammary carcinomas, lympho-proliferative disease (e.g. Hodgkin's and non-Hodgkin lymphomas) and tumours arising from tissue embryologically derived from the neural crest (e.g. paragangliomas, medullary thyroid carcinomas, neuroblastomas, pheochromocytomas). In patients after splenectomy, splenosis should also be considered as a source of false positive results of imaging with gallium (68Ga) edotreotide.
Concomitant use of somatostatin analogues It is preferable to perform imaging with gallium (68Ga) edotreotide the day(s) before the next administration of a somatostatin analogue. See section 4.5.
After the procedure Close contact with infants and pregnant women should be restricted during the initial 8 hours following the injection.
4 Specific warnings Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patients on low sodium diet. This medicinal product contains at maximum 7.4% ethanol, i.e. up to 0.6 g per maximum volume of 10 mL. This amount will produce a blood alcohol concentration of 0.015 g/L (1.5 mg/100 mL) for an adult weighing 70 kg. This is equivalent to 15 mL of beer or 6 mL of wine per maximum dose. This should be taken into account in patients suffering from alcoholism, breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.
Precautions with respect to environmental hazard are in section 6.6.
The maximum volume to be administered to a patient should not exceed 10 mL.
4.5. Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. Somatostatin analogues seem not to compete with Sogacin for binding to somatostatin receptors in target cells. However it is recommended to avoid concurrent treatment with somatostatin analogues with a long half-life for a few days before PET/CT with Sogacin. Somatostatin analogues with a short half-life may be used up to 24 hours before PET/CT with Sogacin.
4.6. Fertility, pregnancy and lactation
Women of childbearing potential When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.
Pregnancy The use of Sogacin is contraindicated in pregnant women due to the radiation exposure to the foetus (see section 4.3).
Breastfeeding Before administering radiopharmaceuticals to a mother who is breastfeeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 8 hours and the expressed feeds discarded.
Close contact with infants should be restricted during this period.
Fertility No studies on fertility have been performed.
4.7. Effects on ability to drive and use machines
Not relevant.
4.8. Undesirable effects
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 4.4 mSv in men and 5 mSv in women when the maximal
5 recommended activity of 200 MBq is administered these adverse reactions 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 reaction via the national reporting system ().
4.9. Overdose
In the event of administration of a radiation overdose with Sogacin the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Diagnostic radiopharmaceuticals, other diagnostic radiopharmaceuticals for tumour detection, ATC code: V09IX09.
Pharmacodynamic effects At the chemical concentrations used for diagnostic examinations, gallium (68Ga) edotreotide does not appear to have any pharmacodynamic activity.
Gallium (68Ga) edotreotide binds in vitro with high affinity mainly to SSTR2 receptors. Edotreotide is a somatostatin analogue. Somatostatin is a neurotransmitter in the central nervous system, but also a hormone which binds to cells of neuroendocrine origin and inhibits the release of growth hormone, insulin, glucagon and gastrin.
Diagnostic performance of gallium (68Ga) edotreotide - In characterisation of bronchial mass as neuroendocrine tumours when other diagnostic modalities are not conclusive: According to results of studies of Kumar et al. (2009), Jindal et al. (2011) and Venkitaraman et al. (2014), the pooled patient based sensitivity of gallium (68Ga) edotreotide in characterisation of pulmonary mass as typical bronchial NET was 100% (43/43) and for characterisation of pulmonary mass as atypical bronchial NET was 44% (5/9).
- In characterisation, staging, detection in case of biochemical recurrence and restaging of neuroendocrine tumours of the foregut, including in the thymus or the bronchi and in characterisation, staging, detection in case of biochemical recurrence and restaging of neuroendocrine tumours of the midgut, when 6-fluoro-(18F)-L-dihydroxyphenylalanine is not available or PET with 6-fluoro-(18F)-L-dihydroxyphenylalanine is non-conclusive: According to results of studies of Ventikaraman et al. (2014), Nakamoto et al. (2014), Gabriel et al. (2007), Frilling et al. (2010) and Schreiter et al. (2014), the pooled patient based sensitivity of gallium (68Ga) edotreotide in detection of the primary NET, in case of proven NET metastasis or rising serum levels of a relevant biochemical tumour marker, was 43% (39/91).
According to results of studies of Hofmann et al. (2001), Gabriel et al. (2007), Putzer et al. (2009), Putzer et al. (2010), Koukouraki et al. (2006), Kumar et al. (2011), Versari et al. (2010), Ruf et al. (2011), Beiderwellen et al. (2013), the pooled patient, based sensitivity of gallium (68Ga) edotreotide in characterisation, staging and restaging of primary and metastatic GEP NET was 93% (200/215) and according to results of studies of Gabriel et al. (2007), Putzer et al. (2009), Versari et al. (2010) and Ruf et al. (2011), the pooled specificity of gallium (68Ga) edotreotide in characterisation, staging and restaging of primary and metastatic GEP NET was 81% (29/36).
6 According to results of studies of Frilling et al. (2010), Gabriel et al. (2007), Froeling et al. (2012), Ruf et al. (2010) and Schraml et al. (2013), the result of functional imaging with gallium (68Ga) edotreotide motivated a change in scheduled therapeutic management in 43% (116/272) of NET patients.
- As an adjunct to anatomic imaging in pre-therapeutic evaluation of meningioma (except peptide receptor radionuclide therapy): According to results of studies of Henze et al. (2001), Henze et al. (2005), Milker-Zabel et al. (2006), Gehler et al. (2009), Nyuyki et al. (2010), Afshar-Oromieh et al. (2012), Graf et al. (2012), Graf et al. (2013), Boss et al. (2010), Afshar-Oromieh et al. (2015), the pooled patient-based detection rate of gallium (68Ga) edotreotide was 99% (310/313). In patients scheduled for radiation therapy of meningioma, the functional imaging with gallium (68Ga) edotreotide led to modification of planned therapeutic volume in 72% (112/155) of patients.
Diagnostic efficacy of gallium (68Ga) edotrotide has not been demonstrated in the pretherapeutic dosimetry evaluation prior to peptide receptor radionuclide therapy targeting somatostatin receptors.
5.2. Pharmacokinetic properties
Distribution Gallium (68Ga) edotreotide is a somatostatin analogue with a strong affinity for somatostatin type 2 receptors.
After intravenous injection, gallium (68Ga) edotreotide is rapidly cleared from the blood following bi- exponential arterial elimination of activity with two half-lives (2.0±0.3 min and 48±7 min).
Organ uptake For certain types of tumours, the high expression of somatostatin receptors is typical, which explains the gallium (68Ga) edotreotide uptake.
Gallium (68Ga) edotreotide shows a physiological uptake in the spleen and the kidneys and to a lesser extent in the liver, the thyroid gland, the adrenal glands and the pituitary.
Elimination Approximately 16% of gallium (68Ga) edotreotide activity is removed from the body in the urine. No radioactive metabolites were detected within 4 hours after intravenous injection of gallium (68Ga) edotreotide in serum.
5.3. Preclinical safety data
Toxicological studies with rats have demonstrated that with a single intravenous injection of gallium (68Ga) edotreotide and 5 mL/kg no deaths were observed.
Mutagenicity studies and long-term carcinogenicity studies have not been carried out. No studies of reproductive function have been performed in animals.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Sodium chloride Ethanol Water for injections
7 6.2. Incompatibilities
This medicinal product must not be mixed with other medicinal products. This medicinal product must not be diluted before injection.
6.3. Shelf life
4 hours from the end of synthesis time.
6.4. Special precautions for storage
This medicinal product does not require any special storage conditions. Do not refrigerate or freeze. Store in the original package. Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
6.5. Nature and contents of the container
25 mL or 15 mL multidose glass vial, colourless Type I glass, closed with a rubber stopper and sealed with an aluminium cap. As a result of the production process Sogacin might be delivered with a punctured rubber septum.
Pack size: One 25 mL vial contains 10 mL of solution with an activity of 200 MBq at the date and time of calibration, corresponding to 200 to 930 MBq per vial at end of synthesis. One 15 mL vial contains 10 mL of solution with an activity of 200 MBq at the date and time of calibration, corresponding to 200 to 930 MBq per vial at end of synthesis.
Multidose vials.
6.6 Special precautions for disposal
General warnings Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent official organisation.
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken in order to meet the demands of pharmaceutical Good Manufacturing Practice.
If at any time in the preparation of the medicinal product the integrity of the vial is compromised it should not be used.
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.
Any unused product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
ITM Medical Isotopes GmbH
8 Lichtenbergstr. 1 85748 Garching Germany Tel: +49 89 329 8986 -600 Fax: +49 89 329 8986 -651 E-mail: [email protected] 8. MARKETING AUTHORISATION NUMBER
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: DD/MM/YYYY
10. DATE OF REVISION OF THE TEXT September 2020 11. DOSIMETRY
Dosimetry of the radiolabelled drug gallium (68Ga) edotreotide was performed using OLINDA/EXM 1.0 software by Hartmann et al. (Hartmann H et al., Radiation exposure of patients during 68Ga- DOTATOC PET/CT examinations, Nuklearmedizin. 2009;48(5):201-7).
Organ Absorbed dose per unit activity administered (mGy/MBq) Men Women Adrenals 0.073 0.084 Bladder wall 0.06 0.013 Bone surfaces 0.015 0.02 Brain 0.0072 0.0095 Breasts 0.0076 0.0098 Gall bladder 0.014 0.017 Gastrointestinal tract Stomach wall 0.011 0.014 Small intestine 0.01 0.013 Upper large intestine 0.012 0.013 Lower large intestine 0.0094 0.013 Heart 0.0099 0.013 Kidneys 0.21 0.25 Liver 0.068 0.082 Lungs 0.0092 0.012 Muscle 0.0087 0.011 Ovaries 0.012 Pancreas 0.015 0.018 Red bone marrow 0.012 0.014 Skin 0.0073 0.0094 Spleen 0.25 0.21 Testes 0.008 Thymus 0.0083 0.0099 Thyroid 0.0079 0.084 Uterus 0.015 Remaining organs 0.012 0.084 Effective dose (mSv/MBq) 0.022 0.025
The effective dose resulting from the administration of a maximal recommended activity of 200 MBq of gallium (68Ga) edotreotide for an adult weighing 70 kg is about 4.4 mSv in men and 5 mSv in women.
9 For an administered activity of 200 MBq the typical radiation doses delivered to the critical organs (bladder wall, spleen, kidneys) are 12 mGy, 50 mGy and 42 mGy in men and 2.6mGy, 42mGy and 50mGy in women, respectively.
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
The pack must be checked before use and the activity measured using an activimeter.
Withdrawals should be performed under aseptic conditions. The vial must not be opened before disinfecting the stopper, the solution should be withdrawn via the stopper using a disposable single dose syringe fitted with suitable protective shielding and a disposable sterile needle or using an authorised automated application system.
If the integrity of this vial is compromised, the product must not be used.
The solution should be inspected visually prior to use. Only clear solutions, free of visible particles should be used.
Detailed information on this product is available on the website of the {name of the Member state Agency}.
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