Difelikefalin

An FDA-approved peripheral kappa opioid receptor agonist for chronic kidney disease-associated itch, without CNS side effects.

StrongWell-Studied

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What is Difelikefalin?

Difelikefalin is a synthetic D-amino acid tetrapeptide that selectively activates peripheral kappa opioid receptors without crossing the blood-brain barrier. It is FDA-approved as Korsuva for moderate-to-severe pruritus (itching) in adults with chronic kidney disease on hemodialysis. Its peripheral selectivity avoids the dysphoria and CNS effects of traditional kappa agonists.

Why People Talk About It

CKD-associated pruritus treatment

Strong

Novel approach to pain without CNS side effects

Emerging

Peripheral opioid signaling without addiction risk

Emerging

How It Works

Difelikefalin activates itch-relief receptors on nerve endings outside the brain. Because it can't enter the brain, it provides relief without the mood changes, sedation, or addiction risk of traditional opioid drugs.

Common Questions

Safety Information

Important Safety Notes

Common Side Effects

DiarrheaDizzinessNauseaHyperkalemia

Cautions

• Only approved for CKD patients on hemodialysis
• Administered by healthcare professionals after dialysis
• Monitor for dizziness

What We Don't Know

Use outside of CKD-associated pruritus is still being studied.

Published Research

30 studies

Efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus: A meta-analysis and systematic review

Meta-AnalysisPMID: 38294219

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials

Meta-AnalysisPMID: 39091079

Pharmacological interventions for pruritus in adult palliative care patients

Meta-AnalysisPMID: 37314034

The Efficacy and Safety of Intravenous Difelikefalin for the Treatment of Pruritus in Patients Undergoing Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Systematic ReviewPMID: 41481512

Association of pruritus with comorbidities and survival in chronic kidney disease: a narrative review of the pre-difelikefalin era literature

Systematic ReviewPMID: 41708519

Difelikefalin in the treatment of hemodialysis patients with pruritus: a systematic review and meta-analysis

Systematic ReviewPMID: 39712488

Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review

Systematic ReviewPMID: 36015082

Systemic Inflammatory Markers Correlate with Chronic Kidney Disease-Associated Pruritus and Response to Treatment

Randomized Controlled TrialPMID: 40409676

Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis

Randomized Controlled TrialPMID: 37968132

Difelikefalin in Black/African American Hemodialysis Patients with Moderate-to-Severe Pruritus: Post hoc Analysis of KALM-1 and KALM-2

Randomized Controlled TrialPMID: 38253036

Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus

Randomized Controlled TrialPMID: 39402448

Difelikefalin for Hemodialysis Patients with Pruritus in Japan

Randomized Controlled TrialPMID: 38320524

Phase 2 Trial of Difelikefalin in Notalgia Paresthetica

Randomized Controlled TrialPMID: 36780675

Assessment of the physical dependence potential of difelikefalin: Randomized placebo-controlled study in patients receiving hemodialysis

Randomized Controlled TrialPMID: 37128642

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial

Randomized Controlled TrialPMID: 35511180

Evaluation of the abuse potential of difelikefalin, a selective kappa-opioid receptor agonist, in recreational polydrug users

Randomized Controlled TrialPMID: 34708917

Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double-blind, placebo-controlled trial

Randomized Controlled TrialPMID: 33982405

Influence of Concomitant Opioids on Difelikefalin Treatment Outcomes in Adults with Moderate-to-Severe Pruritus on Maintenance Hemodialysis: Exploratory Analyses

Phase III Clinical TrialPMID: 41406043

Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis

Phase III Clinical TrialPMID: 40327387

Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial

Clinical TrialPMID: 38196014

Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis

Phase I Clinical TrialPMID: 37369955

A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus

Clinical TrialPMID: 31702883

A phase 2 study of oral difelikefalin in subjects with chronic kidney disease and moderate-to-severe pruritus

Clinical TrialPMID: 37059302

Intravenous difelikefalin for the treatment of hemodialysis pruritus

ReviewPMID: 37847514

Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis

ReviewPMID: 37010031

Difelikefalin: A New κ-Opioid Receptor Agonist for the Treatment of Hemodialysis-Dependent Chronic Kidney Disease-Associated Pruritus