Difelikefalin (Korsuva)
Overview
A selective kappa-opioid receptor (KOR) agonist peptide that does not cross the blood-brain barrier, providing peripheral analgesia and anti-pruritic effects without central opioid side effects such as euphoria, dysphoria, sedation, or addiction. Difelikefalin activates kappa receptors on peripheral sensory neurons and immune cells to reduce itch signaling and inflammation.
Mechanism of Action
Its restricted CNS penetration is a deliberate design feature to avoid abuse potential.
Research Summary & Key Findings
FDA-approved in 2021 for moderate-to-severe pruritus associated with chronic kidney disease (CKD-associated pruritus) in adults undergoing hemodialysis. KALM-1 and KALM-2 trials demonstrated significant reduction in itch intensity vs. placebo, with >40% of patients achieving clinically meaningful itch reduction (Fishbane et al., NEJM, 2020). Oral formulation under development for CKD-associated pruritus in non-dialysis patients and pruritus in liver disease.
Clinical Status
Difelikefalin (Korsuva) has received FDA approval and is available for clinical use under appropriate medical supervision. Consult a qualified healthcare provider for prescribing information.
Administration Routes
References
Primary literature
- PubMed — "Difelikefalin"
Peer-reviewed literature indexed by the National Library of Medicine.
- ClinicalTrials.gov — "Difelikefalin"
Registered interventional and observational studies, including status and phase.
- PubChem — "Difelikefalin"
Chemical structure, molecular properties, and bioactivity data.
Study-level citations for this compound are being verified against the primary sources before publication. The database queries above return the current indexed literature in the meantime.
Related Peptides in Pain
Ziconotide (Prialt)
FDA ApprovedA synthetic 25-amino acid peptide identical to omega-conotoxin MVIIA, a neurotoxin found in the venom of the marine cone...
View detailsARA-290
In Clinical TrialsA synthetic 11-amino acid peptide derived from the structure of erythropoietin (EPO) that selectively activates the inna...
View detailsPalmitoylethanolamide (PEA)
Research PhaseAn endogenous fatty acid amide belonging to the N-acylethanolamine family, naturally produced by cells in response to ti...
View detailsDynorphin A
Research PhaseDynorphin A is an endogenous opioid peptide of 17 amino acids that preferentially binds to and activates kappa-opioid re...
View detailsStart Your Consultation
Get an AI-proposed Difelikefalin (Korsuva) protocol reviewed by a physician in our network.
Start Your ConsultationFind a Pharmacy
Browse PCAB-accredited and FDA 503B-registered compounding pharmacies that supply Difelikefalin (Korsuva).
Pharmacy DirectoryJoin the Association
Access exclusive peptide protocols, provider resources, and community support.
List Your PracticeDisclaimer: This information is provided for educational and research purposes only. It is not intended as medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting any peptide therapy. The Peptide Association does not endorse or recommend any specific treatment protocol. See our editorial policy for how this content is produced and reviewed.