LysaKare

LysaKare is indicated for administration with PRRT with lutetium (177Lu) oxodotreotide. It should therefore only be administered by a healthcare professional experienced in the use of PRRT. Posology Adults The recommended treatment regimen in adults consists of infusion of a full bag of LysaKare concomitantly with lutetium (177Lu) oxodotreotide infusion, even when patients require PRRT dose reduction.

Antiemetics Pre-treatment with an antiemetic 30 minutes prior to the start of LysaKare infusion is recommended to reduce the incidence of nausea and vomiting. In case of severe nausea or vomiting during the infusion of LysaKare despite administration of a preventive antiemetic, an antiemetic of a different pharmacological class can be administered.

Please refer to the full prescribing information of the antiemetic for administration instructions. Special populations Elderly There are limited data on the use of LysaKare in patients aged 65 years or above. 4). 4). 3 Renal impairment Due to the potential for clinical complications related to volume overload and an increase in serum potassium associated with the use of LysaKare, this medicinal product should not be administered in patients with creatinine clearance <30 mL/min.

Care should be taken with LysaKare use in patients with creatinine clearance between 30 and 50 mL/min, due to a potential increased risk of transient hyperkalaemia in these patients. The pharmacokinetic profile and safety of lutetium (177Lu) oxodotreotide in patients with baseline severe renal impairment (creatinine clearance <30 mL/min by Cockcroft-Gault formula) or end-stage renal disease have not been studied.

Treatment with lutetium (177Lu) oxodotreotide in patients with kidney failure with creatinine clearance <30 mL/min is contraindicated. Treatment with lutetium (177Lu) oxodotreotide in patients with baseline creatinine clearance <40 mL/min (using Cockcroft-Gault formula) is not recommended.

No dose adjustment is recommended for renally impaired patients with baseline creatinine clearance ≥40 mL/min and the benefit/risk balance for these patients will therefore always need to be weighed carefully. 4). Paediatric population The safety and efficacy of LysaKare in children aged less than 18 years have not been established.

No data are available. Method of administration For intravenous use. To achieve optimal renal protection LysaKare should be administered as a 4-hour infusion (250 mL/hour) starting 30 minutes prior to administration of lutetium (177Lu) oxodotreotide.

1), which also includes the use of anti-emetics as pre-medication and often the concomitant use of short-acting somatostatin analogues. The main adverse reactions which are related mainly to the amino acid solution are nausea (approximately 25%), vomiting (approximately 10%) and hyperkalaemia.

These adverse reactions are mostly mild to moderate. Tabulated list of adverse reactions The adverse reactions listed below have been identified in publications of studies involving amino acid solutions that had the same composition as LysaKare with regard to amino acid content.

These studies included over 900 patients receiving more than 2 500 doses of arginine and lysine during PRRT with various radiolabelled somatostatin analogues. The adverse reactions are listed according to MedDRA system organ class and by frequency.

The frequencies are categorised 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) and not known (cannot be estimated from the available data).

Table 1 Adverse reactions Adverse reaction Frequency category Metabolism and nutrition disorders Hyperkalaemia Not known Nervous system disorders Dizziness Not known Headache Not known Vascular disorders Flushing Not known Gastrointestinal disorders Nausea Very common Vomiting Very common Abdominal pain Not known 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. 7

Hyperkalaemia A transient increase in serum potassium levels occurs in most patients receiving LysaKare, with maximum serum potassium levels reached approximately 4 to 5 hours after the start of infusion and usually returning to normal levels by 24 hours after the start of the amino acid solution infusion.

Such increases are generally mild and transient. 4). Serum potassium levels must be tested before each administration of LysaKare. If hyperkalaemia is determined, the patient’s history of hyperkalaemia and any concomitant medicinal product should be checked.

1). 1). g. dyspnoea, weakness, numbness, chest pain and cardiac manifestations (conduction abnormalities and cardiac arrhythmias). An electrocardiogram (ECG) should be performed prior to discharging the patient. Vital signs should be monitored during the infusion regardless of baseline serum potassium levels.

g. 1 glass of water every hour) to facilitate elimination of excess serum potassium. If hyperkalaemia symptoms develop during LysaKare infusion, appropriate corrective measures must be taken. In case of severe symptomatic hyperkalaemia, discontinuation of LysaKare infusion should be considered, taking into consideration the risk-benefit of renal protection versus acute hyperkalaemia.

Renal impairment The use of arginine and lysine has not been specifically studied in patients with renal impairment. Arginine and lysine are substantially excreted and reabsorbed by the kidney, and their efficacy in the reduction of renal radiation exposure is dependent on this.

Due to the potential for clinical complications related to volume overload and an increase in serum potassium associated with the use of LysaKare, this medicinal product should not be administered in patients with creatinine clearance <30 mL/min.

Kidney function (creatinine and creatinine clearance) should be tested before each administration. Care should be taken with LysaKare use in patients with creatinine clearance between 30 and 50 mL/min, due to a potential increased risk of transient hyperkalaemia in these patients.

1. 4).