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

Persistent itching is a common and often overlooked burden for people on hemodialysis. 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 translates to itch relief is not fully understood.
• The compound has been studied in at least 23 registered clinical trials, including phase 2 and phase 2/3 work.
• Reported adverse events most often involve dizziness, somnolence, falls, and changes in mental status.
• Difelikefalin has not been studied in patients on peritoneal dialysis and is not recommended for that population.

What Difelikefalin Is

Difelikefalin is a kappa opioid receptor (KOR) agonist, a class of compound that acts on opioid receptors in the body. According to its label, the relevance of this receptor activation to how well the drug works is not established. It is identified in chemical databases under PubChem CID 24794466.

What Difelikefalin Is Approved For

Korsuva is approved to treat moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis. This condition causes persistent itching that can significantly affect quality of life for dialysis patients. The label specifically notes a limitation of use: difelikefalin has not been studied in people on peritoneal dialysis and is not recommended for that group. No boxed warning is present on the label.

What the Evidence Shows

Difelikefalin has been evaluated across 23 registered clinical trials. A completed phase 2 trial examined orally administered difelikefalin (then called CR845) for pain relief in patients with osteoarthritis of the hip or knee. A separate completed phase 2/3 trial tested intravenous difelikefalin specifically in hemodialysis patients with moderate-to-severe pruritus, the population that reflects its approved use. An expanded access program for intravenous difelikefalin has also been listed as approved for marketing.

Reported Side Effects

Adverse event reports submitted to FDA's surveillance system most frequently mention neurological and functional effects: dizziness (45 reports), somnolence (39), and falls (35). Reports of death (29) and drug ineffectiveness (24) have also been logged, along with mental status changes (23), confusional state (19), and nausea (18). These figures reflect raw report counts, not confirmed incidence rates or established causation, and should be interpreted with that limitation in mind.