Korsuva Special Precautions

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See Adverse Reactions for how to report adverse reactions.
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). The incidence of hyperkalemia was higher in patients who took concomitant opioids regardless of study treatment and was almost doubled in the difelikefalin group (11.7%) compared to the placebo group (6.2%). 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 clinical studies a small numerical imbalance of cardiac failure events (4.7%; 20/424 for the difelikefalin treated patients compared to placebo 3.3%; 14/424) and atrial fibrillation events was observed in the difelikefalin (1.4%; 6/424) treated patients compared to placebo (0.5%; 2/424), in particular among patients with a medical history of atrial fibrillation, some of whom had discontinued or missed their atrial fibrillation treatment. The clinical significance of these findings is unknown as 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 Pharmacology: Pharmacodynamics under Actions). 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 Adverse Reactions). 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 Interactions).
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%). Therefore, the use of difelikefalin in this patient population should take into account individual benefit-risk assessment and be carefully monitored.
Excipients with known effect: This medicinal product contains less than 1 mmol sodium per vial, that is to say essentially sodium-free.
Effects on ability to drive and use machines: Somnolence and/or dizziness have been reported in patients receiving difelikefalin (see Adverse Reactions). 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.