SomaKit TOC

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SomaKit TOC 40 micrograms kit for radiopharmaceutical preparation 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of powder contains 40 micrograms of edotreotide. 
 
The radionuclide is not part of the kit. 
 
Excipient with known effect 
The vial of buffer contains approximately 32.5 mg of sodium. 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Kit for radiopharmaceutical preparation containing: 
- Powder for solution for injection: the vial contains a white lyophilised powder. 
- Reaction buffer: the vial contains a clear, colourless solution. 
 
For radiolabelling with gallium (68Ga) chloride solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
This medicinal product is for diagnostic use only. 
 
After radiolabelling with gallium (68Ga) chloride solution, the solution of gallium (68Ga) edotreotide 
obtained is indicated for Positron Emission Tomography (PET) imaging of somatostatin receptor 
overexpression in adult patients with confirmed or suspected well-differentiated gastro-
enteropancreatic neuroendocrine tumours (GEP-NET) for localizing primary tumours and their 
metastases. 
 
4.2 Posology and method of administration 
 
The medicinal product should only be administered by trained healthcare professionals with technical 
expertise in using and handling nuclear medicine diagnostic agents and only in a designated nuclear 
medicine facility. 
 
Posology 
The recommended activity for an adult weighing 70 kg is 100 to 200 MBq, administered by direct 
slow intravenous injection. 
The activity will be adapted to patient characteristics, the type of PET camera used and acquisition 
mode. 
 
Elderly population 
No special dosage regimen for elderly patients is required. 
 

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Renal impairment / Hepatic impairment 
The safety and efficacy of gallium (68Ga) edotreotide have not been studied in patients with renal or 
hepatic impairment. 
 
Paediatric population 
The safety and efficacy of gallium (68Ga) edotreotide has not been established in paediatric 
populations, where the effective dose might be different than in adults. There is no recommendation 
for use of SomaKit TOC in paediatric patients. 
 
Method of administration  
SomaKit TOC is for intravenous use and for single use only. 
This medicinal product should be radiolabelled before administration to the patient. 
 
The activity of gallium (68Ga) edotreotide has to be measured with an activimeter immediately prior to 
injection. 
 
The injection of gallium (68Ga) edotreotide must be administered intravenously in order to avoid local 
extravasation resulting in inadvertent radiation to the patient and imaging artefacts. 
 
For instructions on extemporaneous preparation of the medicinal product before administration, see 
sections 6.6 and 12. 
 
For patient preparation, see section 4.4. 
 
Image acquisition 
Radiolabelled SomaKit TOC is suitable for PET medical imaging. The acquisition must include a 
whole body acquisition from skull to mid-thigh. The recommended time for imaging is 40 to 
90 minutes post injection. Imaging acquisition start time and duration should be adapted according to 
the equipment used, the patient and the tumour characteristics in order to obtain the best image quality 
possible. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the 
components of the labelled radiopharmaceutical. 
 
4.4 Special warnings and precautions for use 
 
Potential for hypersensitivity or anaphylactic reactions 
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be 
discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate 
action in emergencies, the necessary medicinal products and equipment such as endotracheal tube 
must be immediately available. 
 
Individual benefit/risk justification 
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 to obtain the required diagnostic 
information. 
 
Renal / Hepatic 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. 
The safety and efficacy of gallium (68Ga) edotreotide has not been established in paediatric 
populations, where the effective dose might be different than in adults. 

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Patient preparation 
The patient should be well hydrated before the start of the examination and urged to void as often as 
possible, during the first hours after examination in order to reduce radiation. 
 
Interpretation of gallium (68Ga) edotreotide images and limitations of use 
PET images with gallium (68Ga) edotreotide reflect the presence of somatostatin receptors in the 
tissues. 
 
The organs with high physiological uptake of gallium (68Ga) edotreotide include spleen, kidneys, liver, 
pituitary gland, thyroid gland and adrenals. High physiological uptake of gallium (68Ga) edotreotide by 
the pancreas uncinate process can also be observed. 
 
In GEP-NET, a more intense gallium (68Ga) edotreotide uptake than normal background is a consistent 
finding. However, lesions of GEP-NET not expressing sufficient density of somatostatin receptors 
cannot be visualised with gallium (68Ga) edotreotide. PET images with gallium (68Ga) edotreotide 
should be interpreted visually, and semiquantitative measurement of gallium (68Ga) edotreotide uptake 
should not be used for clinical interpretation of images. 
 
Data supporting efficacy of gallium (68Ga) edotreotide for predicting and monitoring of therapeutic 
response to peptide receptor radionuclide therapy (PRRT) in histologically confirmed metastatic NET 
are limited (see section 5.1). 
 
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. Thus, in patients with GEP-NET and Cushing syndrome, 
normalisation of hypercortisolism should be suggested 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. As an 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. thyroid autonomy and Hashimoto’s disease), tumours of the 
pituitary gland, neoplasms of the lungs (small-cell carcinoma), meningiomas, mammary carcinomas, 
lympho-proliferative disease (e.g. Hodgkin's disease and non-Hodgkin lymphomas) and tumours 
arising from tissue embryologically derived from the neural crest (e.g. paragangliomas, medullary 
thyroid carcinomas, neuroblastomas, pheochromocytomas). 
 
Splenectomy should also be considered as a relevant factor when reporting the outcome of 
somatostatin receptor targeted diagnostics. 
 
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 first 8 hours after 
administration. 
 
Specific warnings 
Depending on the time when you administer the injection, the content of sodium may in some cases be 
greater than 1 mmol. This should be taken into account in patient on low sodium diet.  
 
Due to the acidic pH of the radiolabelled gallium (68Ga) edotreotide solution, accidental extravasation 
may cause local irritation. In case of extravasation, the injection must be stopped, the site of injection 
must be changed and the affected area should be irrigated with sodium chloride solution. 

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Precautions with respect to environmental hazard are in section 6.6. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Somatostatin and its analogues are probably competing to bind to the same somatostatin receptors. 
Therefore, when treating patients with somatostatin analogues, it is preferable to perform imaging with 
gallium (68Ga) edotreotide the day(s) preceding the next administration of a somatostatin analogue.  
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 SomaKit TOC. 
 
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 
ionizing radiation (if there are any) should be offered to the patient. 
 
Pregnancy 
No data are available regarding the use of this product during pregnancy. Radionuclide procedures 
carried out on pregnant women also involve radiation doses to the fœtus. Only essential investigations 
should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred 
by the mother and fœtus. 
 
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 the initial 8 hours following injection. 
 
Fertility 
No studies were conducted to assess the impact on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Gallium (68Ga) edotreotide has no or negligible influence on the ability to drive and use machines. 
 
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 about 4.5 mSv when the maximal recommended activity of 
200 MBq is administered, these adverse reactions are expected to occur with a low probability. 
 
Adverse reactions are divided into groups according to the MedDRA convention frequencies: 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). 
 
General disorders and administration site conditions  
Not known: injection site pain 

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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. 
 
4.9 Overdose 
 
In the event of administration of a radiation overdose, the absorbed dose to the patient should be 
reduced where possible by increasing the elimination of the radionuclide from the body by reinforced 
hydration and by frequent micturition. It might be helpful to estimate the effective dose that was 
applied. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other diagnostic radiopharmaceuticals for tumour detection, ATC code: 
V09IX09. 
 
Mechanism of action 
Gallium (68Ga) edotreotide binds to somatostatin receptors. In vitro, this radiopharmaceutical binds 
with high affinity mainly to SSTR2 but also, to a lesser extent, to SSTR5. 
In vivo, semiquantitative correlation was not assessed between gallium (68Ga) edotreotide uptake in 
tumours and the density of SSTR in histopathological samples neither in GEP-NET patients nor in 
normal organs. Moreover, the in vivo binding of gallium (68Ga) edotreotide to structures or receptors 
other than SSTR remains unknown. 
 
Pharmacodynamic effects 
At the chemical concentrations used for diagnostic examinations, gallium (68Ga) edotreotide does not 
appear to have any clinically relevant pharmacodynamic effect. 
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. There is no data if the intravenous administration of 
edotreotide produces variation of serum gastrin and serum glucagon levels. 
 
Clinical efficacy and safety 
For the detection of the primary GEP-NET site in case of rising levels of a relevant biochemical 
tumour marker or in case of proven NET metastasis, patient-based sensitivity and specificity of 
gallium (68Ga) edotreotide PET were 100% (4/4) and 89% (8/9), respectively, in the prospective study 
of Gabriel et al. 2007. Lesion-detection rate was 75% (3/4) in the subgroup of patients with unknown 
primary tumour site of the prospective study of Frilling et al. 2010. In the retrospective paper of 
Schreiter et al. 2014, the intra-individual comparison in a subgroup of 20 patients showed that gallium 
(68Ga) edotreotide permitted to localise the primary tumour in 9/20 (45%) patients while indium (111In) 
pentetreotide did in 2/20 (10%). 
 
A prospective intra-individual comparison showed that gallium (68Ga) edotreotide is able to detect 
lesions better than indium (111In) pentetreotide. A lesion detection rate of 100% (40/40) versus 85% 
(34/40) was observed in the study of Hofmann et al. 2001 recruiting patients with histologically 
proven bronchial (n=2) or midgut (n=6) NETs. In the study of Buchmann et al. 2007, conducted in 
27 patients mostly with GEP-NET (59%) or NETs of unknown primary (30%), gallium (68Ga) 
edotreotide identified 279 lesions versus 157 lesions seen with indium (111In) pentetreotide. In the 
study of Van Binnebeek et al. 2015 in 53 patients with metastatic GEP-NET [mostly GEP-NET (n=39) 
or NET of unknown origin (n=6)], the lesion-based detection rate of gallium (68Ga) edotreotide was 
99.9% (1098/1099) versus 60% (660/1099) for indium (111In) pentetreotide based on the follow-up 

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http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


scans. In the study of Lee et al. 2015 in 13 GEP-NET patients, a total of 35 positive lesions were 
detected in 10 patients on either gallium (68Ga) edotreotide PET/CT or indium (111In) pentetreotide 
SPECT/CT while 3 patients did not exhibit any positive lesions on either imaging method. Gallium 
(68Ga) edotreotide detected 35/35 (100%) lesions vs 19/35=54% for indium (111In) pentetreotide 
SPECT/CT. In the study of Kowalski et al. 2003 in 4 patients with GEP-NET, gallium (68Ga) 
edotreotide showed better patient-based detection rate (100%) than indium (111In) pentetreotide (50%).  
 
Data available on clinical efficacy of gallium (68Ga) edotreotide for the indication of predicting and 
monitoring of therapeutic response to peptide receptor radionuclide therapy (PRRT) in histologically 
confirmed metastatic NET are limited. Five studies have been submitted, one of them prospective 
(Gabriel et al. 2009) and four retrospective studies (Kroiss et al. 2013, Ezziddin et al. 2012, 
Kratochwil et al. 2015 and Luboldt et al.2010a). In the study by Gabriel et al. 2009 pre-PRRT gallium 
(68Ga) edotreotide was compared with CT or MRI using the Response Evaluation Criteria in Solid 
Tumors (RECIST). Gallium (68Ga) edotreotide PET and CT showed a concordant result in 32 patients 
(70%) and discrepancies in 14 patients (30%) presenting 9 with progressive disease and 5 with 
remission. 
 
The retrospective study of Kroiss et al. 2013 in 249 NET patients showed that PRRT does not 
significantly influence semiquantitative uptake of gallium (68Ga) edotreotide PET, except in liver 
metastases of patients with NET, but the study lacked histological confirmation. The three remaining 
retrospective studies recruited small samples (ranging from 20 to 28 GEP-NET patients or those with 
cancer of unknown origin) and found that semiquantitative uptake in the pre-PRRT gallium (68Ga) 
edotreotide PET scan correlated with the tumour-absorbed doses per injected activity of the 
subsequent first treatment cycle, differed between those lesions classified as responding and non-
responding after three PRRT cycles, and helped to separate hepatic metastases from normal liver 
tissue. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
After intravenous injection, gallium (68Ga) edotreotide is rapidly cleared from the blood following bi-
exponential elimination of activity with half-lives of 2.0 ± 0.3 min and 48 ± 7 min respectively. 
 
Organ uptake 
The organ with the highest physiological uptake of gallium (68Ga) edotreotide is the spleen, followed 
by the kidneys. The uptake in the liver and in the pituitary, thyroid and adrenal glands is lower. High 
physiological uptake of gallium (68Ga) edotreotide by the pancreas uncinate process can also be 
observed. About 50 minutes after intravenous administration, gallium (68Ga) edotreotide accumulation 
shows plateauing in all organs. 
The organ uptake has been shown to be age-independent in normal adult human tissues and also 
predominantly gender-independent (except for the thyroid and head of pancreas). 
 
Elimination 
No radioactive metabolites were detected in serum within 4 hours after intravenous injection of 
gallium (68Ga) edotreotide. 
Approximately 16% of gallium (68Ga) edotreotide activity is removed from the body in the urine 
within 2 to 4 hours. The peptide is excreted via kidneys as intact compound. 
 
Half-life 
Given that the elimination rate is substantially slower than the physical half-life of gallium (68Ga) 
(68 min), the biological half-life will have little impact on the effective half-life of the product which 
then would be expected to be somewhat less than 68 minutes. 
 
Renal/Hepatic impairment 
The pharmacokinetics in patients with renal or hepatic impairment has not been characterized. 
 
5.3 Preclinical safety data 

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Non-clinical data did not reveal any special hazard for gallium (68Ga) edotreotide in humans. 
 
Local tolerance assessment resulted in mild to moderate inflammation signs in the perivascular region 
of some animals which can be attributed to the acidic pH of the solution. 
 
No studies on fertility, embryology, mutagenicity or long-term carcinogenicity have been conducted. 
 
Regarding the novel excipient (1,10-phenanthroline), during the toxicity study conducted with the kit 
formulation of SomaKit TOC including 1,10-phenanthroline at a dose 400 fold higher than the human 
dose, no toxicity signs were observed.  
 
Genotoxicity studies on 1,10-phenanthroline available in the literature show negative results in 
bacterial mutation assay (Ames test), while in a mouse lymphoma assay an indication of possible 
genotoxicity was obtained at concentrations 750 times higher than the maximum 1,10-phenanthroline 
blood concentration achievable in patients. However, even taking as worst case reference the limits for 
genotoxic and carcinogenic impurities, the risk related to the trace amounts of 1,10-phenanthroline in 
SomaKit TOC formulation is considered negligible at the dose to be administered in patients: the 
exposure to 1,10-phenanthroline (5 µg/dose) is 24 fold lower than the acceptable daily intake for a 
genotoxic impurity (120 µg/day for exposures <1 month). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
1,10-phenanthroline 
Gentisic acid 
Mannitol (E421) 
 
Buffer 
Formic acid 
Sodium hydroxide (E524) 
Water for injections 
 
After radiolabelling, the solution obtained also contains, as excipient, hydrochloric acid from the 
generator eluate. 
 
6.2 Incompatibilities 
 
Radiolabelling of carrier molecules with gallium (68Ga) chloride is very sensitive to the presence of 
trace metal impurities. Only syringe and syringe needles able to minimise trace metal impurity levels 
(for example, non-metallic or coated with silicone needles – not supplied –) should be used. 
 
This medicinal product must not be mixed with other products except those mentioned in section 12. 
 
6.3 Shelf life 
 
Kit as packaged for sale 
12 months. 
 
After radiolabelling 
4 hours.  
Do not store above 25°C after radiolabelling. 

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From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C to 8°C). 
Store in the original package in order to protect from light. 
For storage conditions after radiolabelling of the medicinal product, see section 6.3. 
 
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive 
materials. 
 
6.5 Nature and contents of container and special equipment for use 
 
Each pack contains: 

• One vial of powder for solution for injection: 10 ml Type I glass vial closed with a  
bromobutyl rubber stopper and sealed with a flip-off cap. Each vial contains 
40 micrograms of edotreotide. 

• One vial of buffer: 10 ml cyclic olefin polymer vial closed with a teflon stopper and sealed 
with a flip-off cap. Each vial contains 1 ml of reaction buffer. 

 
6.6 Special precautions for disposal and other handling 
 
General warnings 
Radiopharmaceuticals should be received, used and administered only by authorized persons in 
designated clinical settings. Their receipt, storage, use, transfer, and disposal are subject to the 
regulations and/or appropriate licenses of the competent official organization.  
 
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and 
pharmaceutical quality requirements. Appropriate aseptic precautions should be taken. 
 
Contents of the vials are intended only for use in the preparation of gallium (68Ga) edotreotide solution 
for injection and are not to be administered directly to the patient without first undergoing the 
preparative procedure.  
 
Each 40 microgram vial contains an excess of product. However, it is recommended that the vial be 
prepared as instructed and used for a single patient dose, based on the activity to be injected; any 
remaining material should be discarded after radiolabelling and use. 
 
Precautions to be taken before handling or administration of the medicinal product 
For instructions on radiolabelling of the medicinal product before administration, see section 12.  
 
If at any time in the preparation of this product the integrity of the vials is compromised it should not 
be used. 
 
Administration procedures should be carried out in a way to minimize risk of contamination of the 
medicinal product and irradiation of the operators. Adequate shielding is mandatory. 
 
The content of the kit before radiolabelling is not radioactive. However, after gallium (68Ga) chloride 
solution is added, adequate shielding of the final preparation must be maintained. 
 
The administration of radiopharmaceuticals creates risks for other persons from external radiation or 
contamination from spills of urine, vomiting, blood, etc. Radiation protection precautions in 
accordance with national regulations must therefore be taken. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

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7. MARKETING AUTHORISATION HOLDER 
 
Advanced Accelerator Applications 
20 rue Diesel 
01630 Saint Genis Pouilly 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1141/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 08/12/2016 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
11. DOSIMETRY 
 
Gallium-68 decays with a half-life of 68 min to stable zinc-68, 89% through positron emission with a 
mean energy of 836 keV followed by photonic annihilation radiations of 511 keV (178%), 10% 
through orbital electron capture (X-ray or Auger emissions), and 3% through 13 gamma transitions 
from 5 excited levels. 
 
The dosimetry of gallium (68Ga) edotreotide was calculated by Sandstrom et al. (2013), using 
OLINDA/EXM 1.1 software (table 1). 
 

Table 1: Dosimetry of gallium (68Ga) edotreotide 

Absorbed dose in selected organs mGy/MBq 
Organs Mean 
Adrenals 0.077 
Brain 0.010 
Breasts 0.010 
Gallbladder wall 0.015 
Lower large intestine wall 0.015 
Small intestine 0.023 
Stomach wall 0.013 
Upper large intestine wall 0.020 
Heart wall 0.020 
Kidneys 0.082 
Liver 0.041 
Lungs 0.007 
Muscle 0.012 
Ovaries 0.015 
Pancreas 0.015 
Red marrow 0.016 
Osteogenic cells 0.021 
Skin 0.010 
Spleen 0.108 

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Absorbed dose in selected organs mGy/MBq 
Organs Mean 
Testes 0.011 
Thymus 0.011 
Thyroid 0.011 
Urinary bladder wall 0.119 
Uterus 0.015 
Total body 0.014 
Effective dose  
mSv/MBq 0.021 

 
The effective dose resulting from the administration of an activity of 200 MBq to an adult weighing 
70 kg is about 4.2 mSv. 
For an administered activity of 200 MBq the typical radiation dose to the critical organs, which are the 
urinary bladder wall, the spleen, the kidneys and the adrenals, are about 24, 22, 16 and 15 mGy, 
respectively. 
 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Radiation safety – Product handling 
Use waterproof gloves, effective radiation shielding, and appropriate safety measures when handling 
the radiolabelled SomaKit TOC to avoid unnecessary radiation exposure to the patient, occupational 
workers, clinical personnel, and other persons. 
 
Radiopharmaceuticals should be used by or under the control of healthcare professionals who are 
qualified by specific training and experienced in the safe use and handling of radionuclides, and whose 
experience and training have been approved by the appropriate governmental agency authorised to 
license the use of radionuclides. 
 
The gallium (68Ga) edotreotide solution must be prepared in accordance with radioprotection and 
pharmaceutical quality standards, especially concerning aseptic technique. If at any time in the 
preparation of this product the integrity of the vials is compromised, the product should not be used. 
 
A low dead space 1 ml plastic syringe must be used in order to precisely measure the adequate volume 
of reaction buffer to be added during the preparation. Glass syringe must not be used. 
 
For administration, the solution should be withdrawn via the stopper using a single dose syringe fitted 
with suitable protective shielding and a disposable sterile needle or using an authorised automated 
application system. 
 
Method of preparation 
SomaKit TOC is supplied as a kit containing two vials. It is intended to be radiolabelled with a 
gallium (68Ga) chloride solution compliant with the Ph. Eur. monograph 2464 Gallium (68Ga) chloride 
solution for radiolabelling and that, in addition, is sterile and has been tested for compatibility with 
SomaKit TOC. Only generators that have been authorised as medicinal products in the EU should be 
used. Refer to the Summary of Product Characteristics of the particular generator for more 
information. 
 
The following authorised generators have shown to be compatible with SomaKit TOC: 

• GalliaPharm, 0.74 – 1.85 GBq, radionuclide generator (Eckert & Ziegler Radiopharma GmbH), 
• Galli Ad, 0.74 – 1.85 GBq, radionuclide generator (IRE-Elit). 

 
The gallium (68Ga) edotreotide solution for intravenous injection must be prepared according to 
aseptic procedure, local regulation and the following instructions. 
 
Reconstitution with GalliaPharm generator: 

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a. If possible, for more convenience in the preparation of radiolabelled SomaKit TOC, the 
heating platform should be placed right beside the generator. 

b. Set the temperature of the shielded dry bath at 95°C and wait for the temperature to reach 
the set point and stabilize. 

c. Flip off cap from the vial of powder and swab the top of the vial closure with an 
appropriate antiseptic to disinfect the surface, and then allow the stopper to dry. 

d. Pierce the Vial 1 septum with a 0.2 µm sterile vent filter in order to maintain atmospheric 
pressure within the vial during the radiolabelling process. 

e. Flip off cap from the Vial 2 (Reaction buffer) and swab the top of the vial closure with an 
appropriate antiseptic to disinfect the surface, and then allow the stopper to dry. With a 
low dead space 1 ml sterile syringe carefully withdraw 0.5 ml reaction buffer, and keep 
the reaction buffer in syringe for step “i”. 

f. Connect the male luer of the outlet line of the 68Ge/68Ga generator with a sterile needle 
(coated with silicone or other appropriate material able to reduce metal impurity trace – 
not supplied). 

g. Connect the Vial 1 to the outlet line of the generator by pushing the needle through the 
rubber septum.  

h. Elute the generator directly into the Vial 1 (through the needle) according to the generator 
manufacturer instructions for use, in order to reconstitute the powder with the eluate. The 
elution can be performed either manually or by means of a pump. 

i. At the end of the elution, disconnect the generator from the Vial 1 withdrawing the needle 
from the rubber septum and immediately add the reaction buffer previously dosed in the 
1 ml sterile syringe. Withdraw the syringe and the 0.2 µm sterile vent filter and move the 
vial to the hole of the dry bath at 95°C, using a plier. Leave the vial at 95°C for at least 
7 minutes (do not exceed 10 minutes heating) without agitation or stirring. 

j. After 7 minutes, remove the vial from the dry bath, place it in an appropriately labelled 
lead shield and let it cool down at room temperature for approximately 10 minutes. 

k. Assay the vial radioactivity using a suitable radioactivity calibration system and record 
the result. Report the activity value, the calibration time, the batch number and the expiry 
time on the shield label included in the pack to be applied on the lead shielding container 
after radiolabelling.  

l. Perform the quality control according to the recommended methods in order to check the 
compliance to the specifications (see section, “Quality control”). 

m. The solution should be visually inspected prior to use. Only clear solutions, free from 
visible particles should be used. The visual inspection should be performed under a 
shielded screen for radioprotection purposes. 

n. Store the vial containing the gallium (68Ga) edotreotide solution below 25°C until use. At 
the time of administration, the product must be aseptically withdrawn and the 
radioprotection standards must be followed. The patient dose should be measured by a 
suitable radioactivity calibration system immediately prior to patient administration. 
Product administration data should also be recorded.  

A schematic representation of the radiolabelling procedure is shown in  
Figure 1. 
 

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Figure 1: Radiolabelling procedure when using GalliaPharm generator 
 
Reconstitution with Galli Ad generator: 

a. If possible, for more convenience in the preparation of radiolabelled SomaKit TOC, the 
heating platform should be placed right beside the generator. 

b. Set the temperature of the shielded dry bath at 95°C and wait for the temperature to reach 
the set point and stabilize. 

c. Flip off cap from the vial of powder and swab the top of the vial closure with an 
appropriate antiseptic to disinfect the surface, and then allow the stopper to dry. 

d. Pierce the Vial 1 septum with a 0.2 µm sterile vent filter in order to maintain atmospheric 
pressure within the vial during the radiolabelling process. 

e. Flip off cap from the Vial 2 (Reaction buffer) and swab the top of the vial closure with an 
appropriate antiseptic to disinfect the surface, and then allow the stopper to dry. With a 
low dead space 1 ml sterile syringe carefully withdraw 100 µl and keep the reaction 
buffer in syringe for step “g”. 

f. With a 5 mL sterile syringe and a sterile needle (coated with silicone or other appropriate 
material able to reduce metal impurity trace – not supplied) carefully withdraw 4 mL of 
water for injections (not supplied) and reconstitute the powder in Vial 1. 

g. Add the reaction buffer previously dosed in the 1 ml sterile syringe. 
h. Connect the male luer of the outlet line of the 68Ge/68Ga generator with a sterile needle 

(coated with silicone or other appropriate material able to reduce metal impurity trace – 
not supplied). 

i. Connect the Vial 1 to the outlet line of the generator by pushing the needle through the 
rubber septum. Turn the button by 90° to loading position then wait 10 seconds before 
turning the button back to initial position, according to the generator’s instructions for 
use. 

j. Connect Vial 1 through the 0.2 µm sterile vent filter to a vacuum vial or to a pump to start 
the elution. Elute the generator directly into the Vial 1 (through the needle). 

k. At the end of the elution, first withdraw the needle from the vacuum vial in order to 
establish atmospheric pressure into Vial 1, then disconnect Vial 1 from the generator by 
removing the needle from the rubber septum. Finally remove the 0.2 µm sterile vent filter 
and move the vial to the hole of the dry bath at 95°C, using a plier. Leave the vial at 95°C 
for at least 7 minutes (do not exceed 10 minutes heating) without agitation or stirring. 

13 



l. After 7 minutes, remove the vial from the dry bath, place it in an appropriately labelled 
lead shield and let it cool down at room temperature for approximately 10 minutes. 

m. Assay the vial radioactivity using a suitable radioactivity calibration system and record 
the result. Report the activity value, the calibration time, the batch number and the expiry 
time on the shield label included in the pack to be applied on the lead shielding container 
after radiolabelling. 

n. Perform the quality control according to the recommended methods in order to check the 
compliance to the specifications (see section, “Quality control”). 

o. The solution should be visually inspected prior to use. Only clear solutions, free from 
visible particles should be used. The visual inspection should be performed under a 
shielded screen for radioprotection purposes. 

p. Store the vial containing the gallium (68Ga) edotreotide solution below 25°C until use. At 
the time of administration, the product must be aseptically withdrawn and the 
radioprotection standards must be followed. The patient dose should be measured by a 
suitable radioactivity calibration system immediately prior to patient administration. 
Product administration data should also be recorded.  
 

A schematic representation of the radiolabelling procedure is shown in Figure 2. 
 

 
 
Figure 2: Radiolabelling procedure when using Galli Ad generator 
 
Gallium (68Ga) edotreotide solution is stable up to 4 hours after preparation. Therefore, the 
radiolabelled solution can be used within 4 hours after preparation according to the radioactivity 
required for the administration. 
 
Radioactive waste must be disposed of in accordance with relevant national regulations. 
 
After radiolabelling with the correct volume of reaction buffer and generator eluate, any further 
dilution with any diluent is prohibited. 
 
Quality control 

Table 2: Specifications of the gallium (68Ga) edotreotide 

Test Acceptance Criteria Method 

Appearance Clear solutions free of visible particles Visual inspection 

pH 3.2 – 3.8 pH-indicator strips 

Labelling efficiency  ≤ 3% 
Thin layer chromatography 
(ITLC1, see details below) 

14 



Test Acceptance Criteria Method 
colloidal gallium-68 species 

Labelling efficiency 
% Free gallium-68 

≤ 2% 
Thin layer chromatography 
(ITLC2, see details below) 

 
The quality controls should be performed under a shielded screen for radioprotection purposes. 
 
Recommended method for determining labelling efficiency of gallium (68Ga) edotreotide: 
 
ITLC1: 
Material 

• Glass-fibre ITLC paper (e.g. Agilent ITLC SGI001) pre-cut to 1 cm x 12 cm strips  
• Mobile phase: 77 g/L solution of ammonium acetate in water /Methanol 50:50 V/V 
• Developing tank 
• Radiometric ITLC scanner 

 
Sample Analysis 

a. The TLC developing tank is prepared by pouring the mobile phase to a depth of 3 to 4 mm. 
Cover the tank and allow to equilibrate. 

b. Apply a drop of the gallium (68Ga) edotreotide on a pencil line 1 cm from the bottom of the 
ITLC strip. 

c. Place the ITLC strip in the developing tank and allow it to develop for a distance of 9 cm 
from the point of application. 

d. Scan the ITLC with a radiometric ITLC scanner 
e. The retention factor (Rf) specifications are as follows: 

Not complexed gallium (68Ga) = 0 to 0.1 
gallium (68Ga) edotreotide = 0.8 to 1 
 

The labelling efficiency is calculated by integration of peak with Rf = 0 to 0.1 that must be ≤ 3%. 
 
ITLC2: 
Material 

• Glass-fibre ITLC paper (e.g. Agilent ITLC SGI001) pre-cut to 1 cm x 12 cm strips Mobile 
phase: sodium Citrate 0.1 M (pH 5) in water 

• Developing tank 
• Radiometric ITLC scanner 

 
Sample Analysis 

a. The TLC developing tank is prepared by pouring the mobile phase to a depth of 3 to 4 mm. 
Cover the tank and allow to equilibrate. 

b. Apply a drop of the gallium (68Ga) edotreotide solution on a pencil line 1 cm from the 
bottom of the ITLC strip. 

c. Place the ITLC strip in the developing tank and allow it to develop for a distance of 9 cm 
from the point of application. 

d. Scan the ITLC with a radiometric ITLC scanner 
The retention factor (Rf) specifications are as follows: gallium (68Ga) edotreotide = 0.1 to 
0.2 
Free gallium-68 = 0.9 to 1 
 

The labelling efficiency is calculated by integration of peak with Rf = 0.9 to 1.0 that must be ≤ 2%. 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

15 

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


 
  

16 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 

17 



A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 
Gipharma S.r.l. 
Via Crescentino 
13040 Saluggia (VC) 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

  

18 



 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  

19 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  

20 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SomaKit TOC 40 micrograms kit for radiopharmaceutical preparation  
edotreotide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 40 micrograms of edotreotide 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Powder: 1,10-phenanthroline, gentisic acid, mannitol (E421) 
Buffer: formic acid, sodium hydroxide (E524), water for injections 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Kit for radiopharmaceutical preparation 
The box contains: 
- 1 vial of powder 
- 1 vial of buffer  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be radiolabelled with the reaction buffer and a solution of Gallium-68 (68Ga) in HCl provided by a 
germanium (68Ge)/gallium (68Ga) generator. 
 
Intravenous use after radiolabelling. 
For single use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Medicinal product radioactive after radiolabelling. 
 

21 



 
8. EXPIRY DATE 
 
EXP  
 
After radiolabelling, use within 4 hours. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Store in the original package in order to protect from light. 
 
After radiolabelling, store below 25°C.  
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Radioactive waste must be disposed of in accordance with relevant national regulations. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Advanced Accelerator Applications 
20 rue Diesel 
01630 Saint Genis Pouilly 
France  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1141/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 

22 



17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 
  

23 



MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SomaKit TOC 40 micrograms powder for solution for injection 
edotreotide 
IV after radiolabelling  
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 micrograms 
 
 
6. OTHER 
 
 

24 



MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BUFFER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SomaKit TOC  
Reaction buffer 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 

25 



MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SHIELD LABEL TO BE APPLIED AFTER RADIOLABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SomaKit TOC 40 micrograms solution for injection 
Gallium (68Ga) edotreotide 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
Use within 4 hours after radiolabelling. 
 
EXP: ________ Time/Date 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Total activity: ________MBq 
Total volume: ________mL  
Calibration time: ________ Time/Date 
 
 
6. OTHER 
 
Do not store above 25ºC  
 
 

 
 
 
 
 
 

 
  

26 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  

27 



Package leaflet: Information for the user 
 

SomaKit TOC 40 micrograms kit for radiopharmaceutical preparation 
Edotreotide 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your nuclear medicine doctor who will supervise the 

procedure. 
- If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What SomaKit TOC is and what it is used for  
2. What you need to know before SomaKit TOC is used 
3. How SomaKit TOC is used 
4. Possible side effects  
5. How SomaKit TOC is stored 
6. Contents of the pack and other information 
 
 
1. What SomaKit TOC is and what it is used for 
 
This medicine is a radiopharmaceutical product for diagnostic use only. It contains the active 
substance edotreotide. Before it can be used, the powder in the vial is mixed with a radioactive 
substance called gallium (68Ga) chloride to make gallium (68Ga) edotreotide (this procedure is called 
radiolabelling).  
 
Gallium (68Ga) edotreotide contains a small amount of radioactivity. After injection into a vein, it can 
make parts of the body areas visible to doctors during a medical imaging procedure called positron 
emission tomography (PET). This medical procedure obtains images of your organs, to help locate the 
abnormal cells or tumours giving valuable information about your disease. 
 
The use of SomaKit TOC involves exposure to small amounts of radioactivity. Your doctor and the 
nuclear medicine doctor have considered that the clinical benefit from the procedure with the 
radiopharmaceutical outweighs the risk due to radiation. 
 
 
2. What you need to know before SomaKit TOC is used 
 
SomaKit TOC must not be used 
- if you are allergic to edotreotide or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your nuclear medicine specialist before you are given SomaKit TOC: 
- if you experience any signs of allergic reaction (listed in section 4) after previous administration 

of SomaKit TOC; 
- if you have kidney or liver problems (renal or hepatic disease); 
- if you are under 18 years of age; 
- if you have signs of dehydration before and after the examination; 

28 



- if you have others medical conditions, such as high level of cortisol in the body (Cushing 
syndrome), inflammation, thyroid disease, other type of tumour (of pituitary gland, lung, brain, 
breast, immune system, thyroid, adrenal gland or others) or disease of spleen that may affect the 
interpretation of the images; 

- if you have been taking other medicines, such as somatostatin analogues and glucocorticoids, 
which may interact with SomaKit TOC;  

- if you are pregnant or believe you may be pregnant; 
- If you are breast-feeding. 
 
Your nuclear medicine doctor will inform you if you need to take any other special precaution before 
or after using SomaKit TOC. 
 
Before administration of SomaKit TOC 
You should drink plenty of water before the start of the examination in order to urinate as often as 
possible during the first hours after the procedure to ensure that SomaKit TOC is removed as quickly 
as possible from the body. 
 
Children and adolescents 
This medicine is not recommended in patients under 18 years of age because its safety and efficacy 
have not been established in this patient population. 
 
Other medicines and SomaKit TOC 
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other 
medicines, including somatostatin analogues, glucocorticoids (also called corticosteroids), since they 
may interfere with the interpretation of the images. If you are taking somatostatin analogues you might 
be asked to stop your treatment for a short period of time. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your nuclear medicine doctor for advice before you are given this medicine. 
 
You must inform the nuclear medicine doctor before the administration of SomaKit TOC if there is a 
possibility you might be pregnant, if you have missed your period or if you are breast-feeding. 
When in doubt, it is important to consult your nuclear medicine doctor who will supervise the 
procedure. 
 
There is no information about the safety and the efficacy of the use of this medicine during pregnancy. 
Only essential investigations should be carried out during pregnancy, when the likely benefit far 
exceeds any risk to the mother and foetus. 
 
If you are breast-feeding the nuclear medicine doctor may either delay the medical procedure until you 
no longer breast-feed or ask you to stop breastfeeding and to discard this milk until there is no 
radioactivity in your body (8 hours after the administration of SomaKit TOC).  
Please ask your nuclear medicine doctor when you can resume breast-feeding. 
 
Driving and using machines 
It is considered unlikely that SomaKit TOC will affect your ability to drive or to use machines.  
 
SomaKit TOC contains sodium 
This medicine contains 1.5 mmol (or 32.5 mg) sodium per dose. Take this into consideration if you are 
on a controlled sodium diet. 
 
 
3. How SomaKit TOC is used 
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products. SomaKit TOC 
will only be used in special controlled areas. This product will only be handled and given to you by 

29 



people who are trained and qualified to use it safely. These persons will take special care for the safe 
use of this product and will keep you informed of their actions. 
 
The nuclear medicine doctor supervising the procedure will decide on the quantity of SomaKit TOC to 
be used in your case. It will be the smallest quantity necessary to get the desired information.  
The quantity to be administered usually recommended for an adult ranges from 100 MBq to 200 MBq 
(megabecquerel, the unit used to express radioactivity). 
 
Administration of SomaKit TOC and conduct of the procedure  
After radiolabelling, SomaKit TOC is administered by intravenous injection. 
A single injection is sufficient to conduct the test that your doctor needs. 
After injection, you will be offered something to drink and asked to urinate immediately preceding the 
test.  
 
Duration of the procedure 
Your nuclear medicine doctor will inform you about the usual duration of the procedure. 
 
After administration of SomaKit TOC, you should:  
- avoid any close contact with young children and pregnant women for 8 hours after the injection 
- urinate frequently in order to eliminate the product from your body. 
 
The nuclear medicine doctor will inform you if you need to take any special precautions after 
receiving this medicine. Contact your nuclear medicine doctor if you have any questions.  
 
If you have been given more SomaKit TOC than you should 
An overdose is unlikely because you will only receive a single dose under controlled conditions by the 
nuclear medicine doctor supervising the procedure. However, in the case of an overdose, you will 
receive the appropriate treatment. Drinking and emptying your bladder frequently will help remove the 
radioactive substance from your body more quickly. 
 
Should you have any further questions on the use of SomaKit TOC, please ask the nuclear medicine 
doctor who supervises the procedure. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Although no side effects have been reported, a potential risk of allergic reactions (hypersensitivity) 
exists with SomaKit TOC. Symptoms may include: warm flush, redness of the skin, swelling, itching, 
nausea and difficulty breathing. In case of allergic reactions you will receive the appropriate treatment 
from your medical staff. 
 
Not known (frequency cannot be estimated from the available data): 

- Stinging near the injection site 
 
This radiopharmaceutical will deliver low amounts of ionising radiation associated with the least risk 
of cancer and hereditary abnormalities. 
 
Reporting of side effects 
If you get any side effects talk to your nuclear medicine doctor. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 

30 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


5. How SomaKit TOC is stored 
 
You will not have to store this medicine. This medicine is stored under the responsibility of the 
specialist in appropriate premises. Storage of radiopharmaceuticals will be in accordance with national 
regulation on radioactive materials. 
 
The following information is intended for the specialist only. 
 
Keep this medicine out of the sight and reach of children. 
 
SomaKit TOC must not be used after the expiry date which is stated on the carton. The expiry date 
refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). 
Store in the original package in order to protect from light. 
 
After radiolabelling, SomaKit TOC should be used within 4 hours. Do not store above 25°C after 
radiolabelling. 
 
SomaKit TOC must not be used if there are visible signs of deterioration. 
 
Do not throw away any medicines via wastewater or household waste. Wait for the level of 
radioactivity to decay adequately before throwing away radioactive products. These measures will 
help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What SomaKit TOC contains 
- The active substance is edotreotide. One vial of powder contains 40 µg of edotreotide.  
- The other ingredients are: 1,10-phenanthroline, gentisic acid, mannitol, formic acid, sodium 

hydroxide, water for injections. 
 
SomaKit TOC contains sodium (see section 2). 
 
After radiolabelling, the solution obtained also contains hydrochloric acid. 
 
What SomaKit TOC looks like and contents of the pack 
SomaKit TOC is a kit for radiopharmaceutical preparation containing: 
- A glass vial with black flip-off cap containing a white powder. 
- A glass vial with yellow flip-off cap containing a clear and colourless solution. 

 
The radioactive substance is not part of the kit and should be added during the preparation steps before 
injection. 
 
Marketing authorisation holder 
Advanced Accelerator Applications 
20 rue Diesel 
01630 Saint Genis Pouilly 
France 
tel: +33 4 50 99 30 70 
fax: +33 4 50 99 30 71 
e-mail: info@adacap.com 
 
Manufacturer 
Gipharma S. r.l. 
Via Crescentino, 

31 

mailto:info@adacap.com


13040 Saluggia (VC) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
AT, BE, BG, CZ, FR, HR, HU, IS, LU, 
LV, LT, MT, NL, RO, SI, SK 
Advanced Accelerator Applications 
Tel/Tél/Teл/Sími: + 33 4 50 99 30 70 
 
CY, EL 
ΒΙΟΚΟΣΜΟΣ ΑΕΒΕ 
Τηλ: +30 22920 63900 
 
DE 
Advanced Accelerator Applications Germany GmbH 
Tel: +49 228 925 88 30 
 
DK, EE, FI, NO, SE 
SAM Nordic 
Tel/Puh/Tlf: +46-8-7205822 
 
ES 
Advanced Accelerator Applications Ibérica, S.L.U. 
Tel: + 34 976 600 126 
 

IE, UK 
Advanced Accelerator Applications UK Limited 
Tel: + 44 1761 404 277 
 
IT 
Advanced Accelerator Applications (Italy) S.r.l 
Tel: + 39 0125 5612 11 
 
PL 
Advanced Accelerator Applications Polska Sp. z o. o. 
Tel: +48 22 57 21 555 
 
PT 
Advanced Accelerator Applications (Portugal), 
Unipessoal, Lda 
Tel: + 351 211212018 

 

 
This leaflet was last revised in  
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web 
site: http://www.ema.europa.eu 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
The complete SmPC of SomaKit TOC is provided as a separate document in the product package, 
with the objective to provide healthcare professionals with other additional scientific and practical 
information about the administration and use of this radiopharmaceutical. 
 
Please refer to the SmPC.  
  

32 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

33 



Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for edotreotide, the scientific 
conclusions of the CHMP are as follows:  
 
In the previous interval, the MAH for edotreotide kit for radiopharmaceutical preparation had received 
cumulatively 4 non-serious reports of injection site pain, including 3 during the reporting interval, one 
of which was considered highly associated with the radiopharmaceutical. Of note the SmPC advises 
that after radiolabelling, the solution obtained also contains, as excipient, hydrochloric acid from the 
generator eluate.  
In the current reporting interval, the number of cases has increased to 10. Of the 6 additional non-
serious cases, 3 cases describe burning and tingling pain extending from the arm to the neck and 
lasting 20 seconds, which is considered highly probably related to edotreotide. The pH in all 3 cases 
was 3.5. In a further case, the patient experienced stabbing pain extending from the hand to the 
shoulder during the injection and this was reported to be due to the low pH of the solution. Causality 
in these cases is probable. Of note, none of these cases appear to have a previous history of psychiatric 
disorder as a confounding factor. Considering the data, an association with injection site pain is 
plausible given the acidic nature of the solution. It is therefore recommended that Injection site pain is 
labelled in 4.8 of the SmPC of the kit for radiopharmaceutical preparation under SOC General 
disorders and administration site conditions with frequency Not known, with a corresponding update 
to the PL.  
Of note, edotreotide solution for injection contains no hydrochloric acid. The final pH is between 4 
and 8. No cases of injection site pain have been identified with these medicines and no Product 
Information changes are recommended. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for edotreotide the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing edotreotide is unchanged subject to the proposed 
changes to the product information for edotreotide kit for radiopharmaceutical preparation. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 
 
 

 

34 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMSOF THE MARKETING AUTHORISATION(S)