--- title: "Difelikefalin" canonical_url: https://peptidelibrary.app/library/difelikefalin description: "Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis." updated: 2026-11-07 publisher: Peptide Library notice: "Research and educational use only. Not medical advice." --- # Difelikefalin Difelikefalin is an FDA-approved peripheral kappa opioid receptor agonist. Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists. Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis. ## Classification - Type: FDA-approved peripheral kappa opioid receptor agonist - Mechanism class: Kappa Opioid Receptor Agonist - Development stage: Approved product - Regulatory class: FDA-approved medicine ## Mechanism Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists. ## Properties - Molecular formula: C36H53N7O6 - Molecular weight: 679.8 g/mol - CAS number: 1024828-77-0 - Half-life: 23–31 hours in hemodialysis patients before dialysis - Studied routes: Intravenous ## Evidence - Evidence level: FDA Approved - Highest documented: Regulatory review (FDA label) - Human trials: 1 - Controlled human trials: 1 - Preclinical sources: 0 - Latest source: 2020 Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess. ### Studies 1. KORSUVA (difelikefalin) injection — FDA prescribing information, DailyMed. Regulatory label (FDA), human. Population: Adults with moderate-to-severe pruritus associated with chronic kidney disease who are on hemodialysis. In the label's two 12-week trials, 40% and 37% had a 4-point or greater fall in worst-itch score versus 21% and 26% with placebo [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c7b81f2-0fd3-47cb-8b0f-185e07f19c87) 2. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020. 2020. Controlled human trial. Population: Adults on hemodialysis with moderate-to-severe pruritus (n=378). At least a 3-point fall in worst-itch score in 51.9% versus 30.9% with placebo (observed data); diarrhea, dizziness and vomiting were more common with difelikefalin [Source](https://pubmed.ncbi.nlm.nih.gov/31702883/) ## Safety Human safety basis: FDA prescribing information ## Regulatory status Difelikefalin is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines. - FDA status: Approved - Availability: Prescription-Only ## Frequently asked questions ### What is Difelikefalin? Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis. ### How does Difelikefalin work? Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists. ### Is Difelikefalin FDA approved? Yes. Difelikefalin is approved by the FDA, and approved products are prescription medicines. Approval is always for specific indications studied in clinical trials, so an approved status does not mean the compound is approved for every use it is discussed for. Research-chemical material sold under the same name is not the approved product. ### What peptides are similar to Difelikefalin? Compounds most often compared with Difelikefalin include Angiotensin II, Cetrorelix, Corticorelin and Cosyntropin. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ. ## References - [A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus — N Engl J Med, 2020](https://pubmed.ncbi.nlm.nih.gov/31702883/) - [Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis — J Ren Care, 2025](https://pubmed.ncbi.nlm.nih.gov/40327387/) - [Intravenous difelikefalin for the treatment of hemodialysis pruritus — Expert Rev Clin Immunol, 2024](https://pubmed.ncbi.nlm.nih.gov/37847514/) - [Pharmacological interventions for pruritus in adult palliative care patients — Cochrane Database Syst Rev, 2023](https://pubmed.ncbi.nlm.nih.gov/37314034/) - [Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis — Expert Rev Clin Pharmacol, 2023](https://pubmed.ncbi.nlm.nih.gov/37010031/)