Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Hyperkalaemia

Hyperkalaemia frequently occurs in chronic kidney disease patients on haemodialysis. In the placebo- controlled clinical studies a numerically higher rate of adverse events of hyperkalaemia was reported for the difelikefalin treated patients (4.7%; 20 / 424 patients) compared to placebo (3.5%; 15 / 424 patients). No causal relationship was established. Frequent monitoring of potassium levels is recommended.

Cardiac failure and atrial fibrillation

Difelikefalin has not been studied in patients with New York Heart Association class IV heart failure.
In the pivotal clinical studies, a small numerical imbalance of cardiac failure and atrial fibrillation events was observed in the difelikefalin treated patients compared to placebo, in particular among patients with a medical history of atrial fibrillation who discontinued or missed their atrial fibrillation treatment. No causal relationship was established.

Patients with impaired blood-brain barrier

Difelikefalin is a peripherally acting kappa opioid receptor agonist with restricted access to the central nervous system (CNS). The blood-brain barrier (BBB) integrity is important for minimizing difelikefalin uptake into the CNS (see section 5.1). Patients with clinically important disruptions to the BBB (e.g., primary brain malignancies, CNS metastases or other inflammatory conditions, active multiple sclerosis, advanced Alzheimer’s disease) may be at risk for difelikefalin entry into the CNS.
Korsuva should be prescribed with caution in such patients taking into account their individual benefit-risk balance with observation for potential CNS effects.

Dizziness and somnolence

Dizziness and somnolence have occurred in patients taking difelikefalin and may subside over time with continued treatment (see section 4.8). Concomitant use of sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of these adverse reactions and should be used with caution during treatment with difelikefalin (see section 4.5).
Compared to placebo, the incidence of somnolence was higher in difelikefalin treated subjects 65 years of age and older (7.0%) than in difelikefalin treated subjects less than 65 years of age (2.8%).

Excipients with known effect

This medicinal product contains less than 1 mmol sodium per vial, that is to say essentially sodium- free.

Effects on Driving

4.7    Effects on ability to drive and use machines

Korsuva has minor influence on the ability to drive and use machines.
Somnolence and/or dizziness have been reported in patients receiving difelikefalin (see section 4.8).
Patients should be cautioned about driving or operating hazardous machinery until the effect of difelikefalin on the patient’s ability to drive or operate machinery is known. Somnolence occurred within the first 3 weeks of treatment and tended to subside with continued dosing. Dizziness occurred within the first 9 weeks of treatment and was generally transient.