LOCAMETZ Kit for radiopharmaceutical preparation Ref.[50606] Active ingredients: Gallium ⁶⁸Ga gozetotide

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.

To date no outcome data exist to inform subsequent management of patients with high-risk disease when PSMA PET/CT is utilised for primary staging.

Experience of use of gallium (⁶⁸Ga) gozetotide PET for selection of patients for PSMA-based therapy is limited to patients with progressive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy, and to selection of patients for treatment with lutetium (¹⁷⁷Lu) vipivotide tetraxetan. Benefit-risk ratio may not be generalisable to other types of PSMA-based therapy and patients with mCRPC with different prior treatments.

Radiation risk

Gallium (⁶⁸Ga) gozetotide contributes to the patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling, reconstitution and radiolabelling procedures should be ensured to protect patients and healthcare professionals from unintentional radiation exposure (see sections 6.6 and 12).

Interpretation of gallium (⁶⁸Ga) gozetotide images

PET images with gallium (⁶⁸Ga) gozetotide should be interpreted by visual assessment. Suspicion of malignant lesions is based on gallium (⁶⁸Ga) gozetotide uptake in comparison with tissue background.

Gallium (⁶⁸Ga) gozetotide uptake is not specific to prostate cancer and may occur in normal tissues (see section 5.2), other types of cancers and non-malignant processes, potentially leading to false positive findings. Moderate to high physiological PSMA uptake is noted in the kidneys, lacrimal glands, liver, salivary glands and urinary bladder wall. False positive findings include, but are not limited to, renal cell carcinoma, hepatocellular carcinoma, breast cancer, lung cancer, benign bone diseases (e.g. Paget’s disease), pulmonary sarcoidosis/granulomatosis, gliomas, meningiomas, paragangliomas and neurofibromas. Ganglia can mimic lymph nodes.

The diagnostic performance of gallium (⁶⁸Ga) gozetotide may be affected by serum PSA levels, androgen-receptor-targeting treatments, disease stage and size of malignant lymph nodes (see section 5.1).

Gallium (⁶⁸Ga) gozetotide PET images should be interpreted only by readers trained in the interpretation of PET images with gallium (⁶⁸Ga) gozetotide PET. Findings on gallium (⁶⁸Ga) gozetotide PET images should always be interpreted in conjunction with and be confirmed by other diagnostic methods (including histopathology) before subsequent change in patient management is initiated.

Patient preparation

Patients should be well hydrated prior to gallium (⁶⁸Ga) gozetotide administration and should be advised to void immediately prior to and frequently during the first hours after image acquisition in order to reduce radiation exposure.

Specific warnings

Sodium content

This medicinal product contains 28.97 mg sodium per injection, equivalent to 1.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Acidic pH and extravasation

Low pH of gallium (⁶⁸Ga) gozetotide may lead to injection site reactions after administration. Accidental extravasation may cause local irritation, due to the acidic pH of the solution. Cases of extravasation should be managed as per institutional guidelines.

Based on in vitro interaction studies, gallium (⁶⁸Ga) gozetotide is not expected to have any clinically significant interaction with other medicinal products (see section 5.2). No interaction studies have been performed.

Pregnancy

Locametz is not indicated for use in females. There are no data on the use of gallium (⁶⁸Ga) gozetotide in females. Reproductive toxicity studies in animals have not been conducted with gallium (⁶⁸Ga) gozetotide. However, all radiopharmaceuticals, including gallium (⁶⁸Ga) gozetotide, have the potential to cause foetal harm.

Breast-feeding

Locametz is not indicated for use in females. There are no data on the effects of gallium (⁶⁸Ga) gozetotide on the breast-fed newborn/infant or on milk production. Lactation studies have not been conducted in animals with gallium (⁶⁸Ga) gozetotide.

Fertility

There are no data on the effect of gallium (⁶⁸Ga) gozetotide on human fertility.

Gallium (⁶⁸Ga) gozetotide has no or negligible influence on the ability to drive and use machines.

Summary of safety profile

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 0.0166 mSv/MBq, with a maximal recommended dose of 259 MBq (4.3 mSv), these adverse reactions are expected to occur with a low probability.

Mild to moderate adverse reactions occurred in patients receiving gallium (68Ga) gozetotide, with the exception of a grade 3 fatigue event (0.1%).

The most common adverse reactions are fatigue (1.2%), nausea (0.8%), constipation (0.5%) and vomiting (0.5%).

Tabulated list of adverse reactions

The safety profile of gallium (68Ga) gozetotide at median dose per body weight of 1.9 MBq/kg (range: 0.9-3.7 MBq/kg) was evaluated in 1 003 patients with metastatic castration-resistant prostate cancer receiving physician’s discretion for best standard of care (VISION study).

Adverse reactions (Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention (CIOMS III): 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).

Table 1. Adverse reactions observed with gallium (68Ga) gozetotide:

¹ Injection site reactions includes: injection site haematoma, injection site warmth, injection site pruritus

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.

This medicinal product must not be mixed with other medicinal products except those mentioned in sections 6.6 and 12.