An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease

Zoe M. Lipman, Gil Yosipovitch

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Introduction: Chronic kidney disease-associated pruritus (CKD-aP), or uremic pruritus, is a severely distressing condition that occurs in greater than 60% of patients undergoing dialysis. However, there are currently no FDA approved treatments for CKD-aP in the United States or Europe. Difelikefalin (DFK) is a kappa opioid receptor agonist with limited central nervous system (CNS) penetration that aims to fill this void by effectively and safely reducing itch in these patients. Areas covered: Through a review of the current literature (using PubMed and Google Scholar keyword searches of difelikefalin, CR845, pruritus, itch, opioids, hemodialysis, chronic kidney disease, uremic pruritus), the authors review DFK’s mechanism of action and use published clinical trial data to evaluate its effectiveness in treating CKD-aP both individually and comparatively to other treatment alternatives. Expert opinion: DFK’s IV formulation seems to provide safe, rapid-acting and effective itch reduction in hemodialysis patients without many of the negative mu opioid receptor (MOR)- or CNS- related side effects or drug-drug interactions of other currently available opioids. Its administration through IV bolus immediately after dialysis sessions at dialysis centers also increases availability to and ease of drug scheduling for this target population.

Original languageEnglish (US)
Pages (from-to)549-555
Number of pages7
JournalExpert Opinion on Pharmacotherapy
Issue number5
StatePublished - 2021
Externally publishedYes


  • CR845
  • Chronic kidney disease associated pruritus
  • Difelikefalin
  • end stage renal disease
  • hemodialysis associated pruritus
  • itch
  • kappa opioid agonist
  • peripherally restricted kappa opioid agonist
  • pruritus
  • uremic pruritus

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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