Difelikefalin (Korsuva): Uses, Evidence, and Side Effects

Chronic itch tied to kidney disease can be relentless for people on hemodialysis, disrupting sleep and daily life. Difelikefalin, sold as Korsuva, is an FDA-approved option developed specifically for this problem.

Key takeaways

• Difelikefalin (Korsuva) is approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on hemodialysis.
• It works as a kappa opioid receptor agonist, though how this activity produces relief is not fully established.
• It is not recommended for patients on peritoneal dialysis, since it has not been studied in that group.
• 23 registered trials include completed Phase 3 work supporting its approval for dialysis-associated itch.
• Reported adverse events most often involve dizziness, somnolence, and falls.

What Difelikefalin Is

Difelikefalin is a kappa opioid receptor (KOR) agonist. The label notes that the relevance of KOR activation to how well the drug works is not known. It is identified in chemical databases under PubChem CID 24794466.

What Difelikefalin Is Approved For

Difelikefalin, marketed as Korsuva, is approved to treat moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis. The label specifically limits its use to this hemodialysis population. It has not been studied in patients on peritoneal dialysis and is not recommended for that group. No boxed warning is listed for this drug.

What the Evidence Shows

Difelikefalin has been studied across 23 registered clinical trials. A completed Phase 2/3 trial evaluated intravenous CR845 (an earlier name for difelikefalin) in hemodialysis patients with moderate-to-severe pruritus. A separate completed Phase 3 global study, CR845-CLIN3103, assessed its safety and efficacy in the same hemodialysis population with pruritus.

Reported Side Effects

Reported side effects reflect counts of adverse event reports submitted to a safety database, not confirmed rates or causation. The most frequently reported reactions center on the nervous system and balance: dizziness (45 reports), somnolence (39), and falls (35). Reports of death (29) and drug ineffectiveness (24) were also recorded, along with mental status changes (23), confusional state (19), and nausea (18).