PYLCLARI Solution for injection Ref.[51072] Active ingredients: Piflufolastat ¹⁸F

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 and ventilator 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 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

The patient should be well hydrated before the start of the examination and urged to void before the examination in order to reduce bladder activity and as often as possible during the first hours after the examination in order to reduce radiation exposure.

A diuretic expected to act within the uptake time period may be administered to improve interpretation of piflufolastat (¹⁸F) PET/CT as it results in less activity depositions in ureters and the bladder.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Interpretation of piflufolastat (¹⁸F) images

The recommended method for PET images interpretation with piflufolastat (¹⁸F) PET/CT is the visual interpretation.

Lesions should be considered suspicious if uptake is greater than physiologic uptake in that tissue or greater than adjacent background if no physiologic uptake is expected.

Piflufolastat (¹⁸F) accumulates in normal tissue where the density of PSMA is high including the lacrimal glands, salivary glands, liver, spleen, and kidneys. Normal organs demonstrate significant variability in the uptake of piflufolastat (¹⁸F); however, the impact of tumor burden on normal uptake is minimal and unlikely to be clinically significant. The expression of PSMA can predominantly be found in prostate cancer, but can also be observed in other neoplasms (e.g. renal cell carcinoma, hepatocarcinoma, breast cancer, lung cancer and other malignancies) or non-malignant conditions (e.g hemangioma, ganglia, since they can mimic lymph nodes, benign bone disease as Paget’s disease, or pulmonary sarcoidosis/granulomatosis).

Images should be interpreted only by readers trained in the interpretation of PET images with piflufolastat (¹⁸F).

Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer.

Piflufolastat (¹⁸F) was not studied for detection of distant metastases in primary staging.

The performance of piflufolastat (¹⁸F) for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels (see section 5.1). The performance of piflufolastat (¹⁸F) for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score.

Small lymph nodes metastases, or any lesion under spatial resolution of PET (= 5 mm) may be missed by piflufolastat (¹⁸F) PET/CT.

To date no outcome data exist to support subsequent management of patients based on PSMA-PET in the primary staging. Therefore, treatment should not be changed based on piflufolastat (¹⁸F) PET/CT findings only.

Specific warnings

This medicinal product contains up to 3.5 mg sodium per mL equivalent to 0.2 % to the WHO recommended maximum daily intake of 2 g sodium for an adult.

This medicinal product contains up to 900 mg of alcohol (ethanol) in each administration which is equivalent to 90 mg per mL. The amount in 10 mL of this medicinal product is equivalent to less than 23 mL of beer or 11 mL of wine.

The small amount of alcohol in this medicinal product will not have any noticeable effects.

No interaction studies have been performed.

Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of piflufolastat (¹⁸F) in prostate cancer. The effect of these therapies on performance of piflufolastat (¹⁸F) PET has not been established.

Chronic treatment with diuretics does not seem to have any interference with piflufolastat (¹⁸F) for interpretation of images.

Pregnancy

Piflufolastat (¹⁸F) is not intended for use in women.

Breast-feeding

Piflufolastat (¹⁸F) is not intended for use in women.

Fertility

No studies on fertility have been performed.

Pylclari has no or negligible influence on the ability to drive and use machines.

Summary of safety profile

The overall safety profile is based on data from its administration to 797 patients from three clinical studies and spontaneous reporting. In the clinical studies, each patient received a single administration with a median administered activity of 330 MBq. Adverse reactions have been reported during clinical development and are listed below by MedDRA body system organ class.

Tabulated list of adverse reactions

The frequencies of adverse reactions are defined as follows: Very common (≥1/10), common (≥1/100 to <1/10), Uncommon (≥1/1 000 to <1/100), Rare (≥1/10 000 to <1/1 000), Very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions observed with piflufolastat (¹⁸F):

^* Adverse reactions derived from spontaneous reporting with a not known frequency.

Description of selected adverse reactions

A total of 108 treatment emergent adverse events (TEAEs) were reported in 69 (8.6%) patients, with headache (1.4%), dysgeusia (1.0%), and fatigue (0.5%) being the most frequent. Three serious drugrelated adverse events (hypersensitivity, headache, and paresthesia) were reported, all experienced by one patient and only hypersensitivity was assessed as drug-related in this patient who had a significant history of allergic reactions. All three serious drug-related adverse events were resolved.

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects.

As the effective dose is 4.2 mSv when the maximal recommended activity of 360 MBq is administered in a 70 kg-weighted patient, 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 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 section 12.