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Pain & nerve

Difelikefalin

Also called Korsuva, Kapruvia, CR845

Difelikefalin is a small lab-made peptide that switches on kappa opioid receptors, mostly outside the brain. It is an IV drug given at the end of dialysis to relieve the severe itch many kidney-failure patients get.

FDA-approvedApproved by the FDA for at least one use after large human trials.

All printable flashcards

Drawn from its published sequence: 5 residues, one bead each.

Overview

Difelikefalin is a small lab-made peptide that switches on kappa opioid receptors, mostly outside the brain. It is an IV drug given at the end of dialysis to relieve the severe itch many kidney-failure patients get.

How it works

Established: difelikefalin is a kappa opioid receptor agonist (FDA label). Proposed: its D-amino-acid, highly polar design limits entry into the brain, so it is thought to act mainly on peripheral nerves and immune cells that drive itch. The label notes that exactly how KOR activation relieves itch is not known.

What research shows

  • Two phase 3 RCTs in hemodialysis patients (KALM-1, 378 patients; KALM-2, 473): a 4-point or greater itch-score improvement at week 12 in 40% vs 21% and 37% vs 26% on placebo (FDA label).
  • Not studied in peritoneal dialysis (FDA label).

Doses studied in people

Study or labelDose usedSource
FDA label (Korsuva), CKD-associated pruritus in adults on hemodialysis0.5 mcg/kg (dry body weight) IV bolus at the end of each hemodialysis session, three times weekly1

Given only in the dialysis unit, into the dialysis circuit, per the label.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Safety

  • Dizziness, sleepiness, mental status changes and gait problems including falls: 17.0% vs 12.0% on placebo; sleepiness more frequent in people 65 and older (FDA label).
  • Use caution with other sedating drugs, sedating antihistamines and opioids; may impair driving (FDA label).
  • Common vs placebo: diarrhea 9.0% vs 5.7%, dizziness 6.8% vs 3.8%, nausea 6.6% vs 4.5%, hyperkalemia 4.7% vs 3.5% (FDA label).

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Storage and stability

Vials at 20-25°C; do not freeze; give within 4 hours of drawing up (FDA label).

General lab handling, not instructions for personal use. See Storage and stability.

History

Developed by Cara Therapeutics (as CR845), first studied for post-surgical pain. The FDA approved the IV form as Korsuva in August 2021, the first drug for chronic-kidney-disease itch in hemodialysis patients; the EU approved it as Kapruvia in April 2022 (marketed by Vifor). An oral form was also studied.

Common questions

Is difelikefalin FDA-approved?

Yes. It was approved as Korsuva in 2021 for moderate to severe itch from chronic kidney disease in adults on hemodialysis 1. It is approved in the EU as Kapruvia 2.

Is difelikefalin an opioid?

It switches on kappa opioid receptors, but the label notes exactly how this relieves itch is not known 1. The label states it is not a DEA-controlled substance 1.

What does the research show?

In two phase 3 trials in hemodialysis patients, 40% versus 21% and 37% versus 26% on placebo had a meaningful drop in itch score at week 12 1. It has not been studied in peritoneal dialysis 1.

What dose is on the FDA label?

The label lists 0.5 mcg/kg of dry body weight by IV at the end of each hemodialysis session, three times a week 1. It is given only in the dialysis unit 1.

What are the side effects?

Dizziness, sleepiness, confusion and walking problems including falls occurred in 17.0% versus 12.0% on placebo 1. Diarrhea, nausea and high potassium were also more common, and it may impair driving 1.

Is difelikefalin banned in sport?

It is not named on WADA's 2026 Prohibited List 90.

Related compounds

Pain & nerveFDA-approvedFlashcard

Ziconotide

Prialt · SNX-111

Ziconotide is a lab-made copy of a toxin from a fish-hunting cone snail.

Sources

  1. KORSUVA (difelikefalin) prescribing information FDA label
  2. Difelikefalin (Wikipedia; structure, CAS, approvals) Journal
  3. WADA 2026 Prohibited List Regulatory

Last reviewed 2026-10-25 · How we research · Found an error? See our corrections policy.