LYSAKARE Solution for infusion Ref.[49640] Active ingredients: Arginine Lysine

Hyperkalaemia

An increase of serum potassium levels may occur in patients receiving arginine and lysine. Serum potassium level increases are generally mild and transient. According to limited available data maximum levels should be reached approximatively by 4 to 5 hours after start of the infusion and should return to normal levels by 24 hours.

Serum potassium levels must be tested before each treatment with LysaKare. In case of hyperkalaemia, patient’s history of hyperkalaemia and concomitant medication should be checked. Hyperkalaemia must be corrected accordingly before starting the infusion (see section 4.3).

In case of pre-existing clinically significant hyperkalaemia, a second monitoring prior to LysaKare infusion must confirm that hyperkalaemia has been successfully corrected. The patient should be monitored closely for signs and symptoms of hyperkalaemia, e.g. dyspnoea, weakness, numbness, chest pain and cardiac manifestations (conduction abnormalities and cardiac arrhythmias). An ECG should be performed prior to discharging the patient.

Vital signs should be monitored during the infusion regardless of baseline serum potassium levels. Patients should be instructed to drink substantial quantities of water (at least 1 glass every hour) on the day of infusion to remain hydrated and facilitate excretion of excess serum potassium.

In case 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.

Patients with 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 of potassium in blood associated with the use of LysaKare, this 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. Treatment with lutetium (¹⁷⁷Lu) oxodotreotide is not recommended for patients with renal function between 30 and 50 mL/min therefore, the benefit risk for these patients will always need to be weighed carefully, which should include consideration of an increased risk for transient hyperkalemia in these patients.

Patiens with hepatic impairment

The use of arginine and lysine has not been studied in patients with severe hepatic impairment. Liver function (alanine aminotransferase [ALAT], aspartate aminotransferase [ASAT], albumin, bilirubin) should be tested before each administration.

Care should be taken with LysaKare use in patients with severe hepatic impairment and in case of either total bilirubinemia >3 times the upper limit of normal or albuminemia <30 g/L and prothrombin ratio <70% during treatment. Treatment with lutetium (¹⁷⁷Lu) oxodotreotide is not recommended in these circumstances.

Heart failure

Due to potential for clinical complications related to volume overload care should be taken with use of arginine and lysine in patients with severe heart failure defined as class III or class IV in the NYHA classification.

Treatment with lutetium (¹⁷⁷Lu) oxodotreotide is not recommended for patients with severe heart failure defined as class III or class IV in the NYHA classification therefore, the benefit risk for these patients will always need to be weighed carefully.

Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in determining eligibility based on creatinine clearance.

Metabolic acidosis

Metabolic acidosis has been observed with complex amino-acid solutions administered as part of total parenteral nutrition (TPN) protocols. Shifts in acid-base balance alter the balance of extracellular-intracellular potassium and the development of acidosis may be associated with rapid increases in plasma potassium.

As LysaKare is administered with lutetium (¹⁷⁷Lu) oxodotreotide, please also refer to section 4.4 of the lutetium (¹⁷⁷Lu) oxodotreotide SmPC for further warnings specific to treatment with lutetium (¹⁷⁷Lu) oxodotreotide.

No interaction studies have been performed.

No interaction with other medicinal product is expected since there is no information that other drugs are re-absorbed by the same kidney re-absorption mechanism.

There is no relevant use of this medicinal product in women of childbearing potential since lutetium (¹⁷⁷Lu) oxodotreotide is contraindicated during established or suspected pregnancy or when pregnancy has not been excluded due to the risk associated with the ionizing radiation (see section 4.1).

Pregnancy

There are no data on the use of arginine and lysine in pregnant women.

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

Breast-feeding

Arginine and lysine, being naturally occurring amino acids, are excreted in human milk, but effects on the breastfed newborns/infants are unlikely. Breast-feeding should be avoided during treatment with lutetium (¹⁷⁷Lu) oxodotreotide.

Fertility

There are no data on the effects of arginine and lysine on fertility.

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

Summary of the safety profile

There are very limited data on the safety profile of arginine and lysine solution for infusion without concomitant administration of PRRT, 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 with amino acid solutions with the same composition with regards to the amino acid content, involving 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 the 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 drug reactions:

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.