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 localising 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

No special dose regimen for elderly patients is required.

Renal/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 have 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 must 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 the top of the 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 use in the paediatric population, see section 4.2.

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 exposure.

Errors of interpretation of gallium (68Ga) edotreotide images

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.

An increased uptake of gallium (68Ga) edotreotide is not specific for GEP-NET. Healthcare professionals should be aware that further imaging or histological and/or other relevant investigations may be required to establish the diagnosis.

Due to physiological uptake of gallium (68Ga) edotreotide, splenosis and accessory intrapancreatic spleen may be incidentally detected with somatostatin receptor targeted diagnostics. Cases in which such uptake has been misdiagnosed as neuroendocrine tumours, leading to unnecessary intervention, have been reported. Spleen disorders (e.g. splenectomy, splenosis and accessory intrapancreatic spleen) should therefore be considered as a relevant factor when reporting the outcome of somatostatin receptor targeted diagnostics.

Positive results also 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, including reactive lymph nodes, for example following vaccination), 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, lymphoproliferative 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).

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.

Limitations of gallium (68Ga) edotreotide imaging

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).

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 12 hours after administration.

Specific warnings

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium-free'.

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.

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.

Some evidence exists that glucocorticoids can induce down-regulation of somatostatin subtype 2 receptors (SSTR2). Repeated administration of high doses of glucocorticoids prior to gallium (68Ga) edotreotide administration may cause insufficient SSTR2 expression for adequate visualisation of somatostatin receptor-positive NETs.

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 her periods are very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

No data are available regarding the use of this medicinal product during pregnancy. Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus.

Breast-feeding

Before administering radiopharmaceuticals to a mother who is breast-feeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breast-feeding, 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, breast-feeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during the initial 12 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

Description of selected adverse reactions

Cases in which physiological uptake of gallium (68Ga) edotreotide by splenic tissue has been misdiagnosed as neuroendocrine tumour, leading to unnecessary intervention, have been reported (see section 4.4).

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:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 through reinforced hydration and frequent micturition. It might be helpful to estimate the effective dose that was applied.