PYLCLARI

This medicinal product is for use in designated nuclear medicine facilities only and should only be handled by authorised personnel. Posology The mean recommended activity of (18F) piflufolastat is 4 MBq/kg of body weight and can vary from 3 to 5 MBq/kg of body weight depending on the PET equipment and acquisition mode used.

The minimum activity should not fall below 190 MBq and the maximum activity should not exceed 360 MBq. Renal impairment / Hepatic impairment Piflufolastat (18F) has only been studied in patients with mild renal impairment. Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in patients with severe impaired renal function.

Piflufolastat (18F) has not been studied in patients with hepatic impairment. Paediatric population There is no relevant use of piflufolastat (18F) in the paediatric population. Method of administration It is administered by a single intravenous injection.

Pylclari is presented in multidose vial. 5 ml of solution per vial. 2 ml to 10 ml. 6. For instructions on dilution of the medicinal product before administration, see section 12. Image acquisition It is recommended to position the patient supine with arms above the head.

A non contrast-enhanced low-dose CT scan is performed from the vertex of the skull through mid-thigh for attenuation correction and anatomic correlation. The PET acquisition is performed from mid-thigh through the vertex of the skull, starting 90 to 120 minutes after tracer injection.

It must include lower extremities if there is known or suspected disease. Image acquisition duration is 12 to 40 minutes depending on the type of PET cameras, number of bed positions (typically 6 to 8) and acquisition time per bed position (typically 2 minutes to 5 minutes).

If the acquisition leads to indeterminate findings, and provided a sufficient activity remains for adequate counting statistics, late acquisitions can also be performed, thus reducing background activity. 4.

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 (³1/1 000 to <1/100), Rare (³1/10 000 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) MedDRA body system organ class Adverse reactions Frequency Immune system disorders Hypersensitivity Uncommon Metabolism and nutrition disorders Dehydration Uncommon Psychiatric disorders Disorientation Uncommon Syncope Not known* Dysgeusia Headache Common Dizziness Hyperaesthesia Nervous system disorders Migraine Uncommon Eye disorders Visual field defect Uncommon Ear and labyrinth disorders Vertigo Uncommon NauseaGastrointestinal disorders Vomiting Not known* Dry skinSkin and subcutaneous tissue disorders Rash Uncommon Arthralgia Muscular weakness Musculoskeletal and connective tissue disorders Pain in extremity Uncommon Renal and urinary disorders Dysuria Uncommon Fatigue Uncommon Chest discomfort Application site rash Feeling abnormal General disorders and administration site conditions Injection site pain Uncommon *Adverse reactions derived from spontaneous reporting with a not known frequency.

5%) being the most frequent. Three serious drug-related 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.

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.

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.

1.