Difelikefalin
Kappa-opioid agonist peptide
Also Korsuva, Kapruvia, CR845, CR-845, Difelikefalin acetate
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Intravenous
- Studies cited
- 1 human0 animal or cell
It is a drug for the itch that many people on kidney dialysis get. Two trials showed it eased itch better than a dummy drug.
Sold for
Difelikefalin is talked about as an itch drug that works without the sedation or dependence risk of conventional opioids.
Studies say
Two placebo-controlled trials in dialysis patients support the approved use, so the grade is A for uremic pruritus and nothing else.
Why grade A. Approval rests on two randomized, double-blind, placebo-controlled phase 3 trials (KALM-1 and KALM-2) in hemodialysis patients with uremic itch. KALM-1, the trial cited here, randomized 378 patients and met its primary endpoint over 12 weeks. Nothing is missing for the approved use; what is missing is any controlled evidence for itch in people who are not on dialysis, which is where most online interest lies. 12
FDA. Approved. Difelikefalin is sold as Korsuva, approved by the FDA in August 2021 for moderate-to-severe pruritus (itch) associated with chronic kidney disease in adults on hemodialysis. It is given intravenously through the dialysis circuit. 2
Written from 2 cited sources. Fact-checked 2026-10-27: 15 claims checked, 2 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Itching in people on kidney dialysis
- Can a US doctor prescribe it?
- Yes, FDA approved for itching in adults on kidney dialysis.
- Properly tested in people?
- Yes, in large controlled trials. The main trial had 378 people.
Evidence checklist
- Randomised controlled trial KALM-1 and KALM-2 placebo-controlledyes
- Human study over 100 people KALM-1, 378 dialysis patientsyes
- More than one research group Two trials; approved by FDA 2021yes
- Clinical outcomes, not surrogate markers Itch severity in dialysis patientsyes
- Human safety data beyond case reports Pooled trials: dizziness, diarrhoea, fallsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Difelikefalin is a synthetic peptide that activates the kappa-opioid receptor. It is built from D-amino acids, which are mirror-image versions of the natural building blocks. This makes it resistant to the enzymes that normally break peptides down. It is also designed so that almost none of it crosses from the blood into the brain. That limit is the point. Kappa-opioid receptors on nerve endings and immune cells in the skin can be targeted. Brain-penetrating kappa agonists cause hallucinations and mood effects. This drug avoids them. 1
The approved product is Korsuva. Cara Therapeutics makes it, and Vifor markets it in the US. Staff give it as an intravenous injection into the venous line of the dialysis circuit. This happens at the end of a hemodialysis session, so patients do not inject it themselves. 2
How it works
Itch linked to chronic kidney disease is thought to involve two things. One is an imbalance between the mu-opioid system, which promotes itch, and the kappa-opioid system, which suppresses it. The other is low-grade inflammation driven by immune cells. Difelikefalin binds kappa receptors on peripheral sensory neurons and on immune cells. This reduces the itch signal and the release of inflammatory messengers. It stays outside the brain. So it does not produce the euphoria of mu-opioid drugs, and it is not a controlled substance. 12
What human research shows
KALM-1 enrolled 378 adults on hemodialysis with moderate-to-severe itch. Researchers randomized them to difelikefalin or placebo after each dialysis session for 12 weeks. The main outcome was the share of patients whose weekly average itch score fell by at least 3 points on a 0-to-10 scale. That happened in 52% of the difelikefalin group and 31% of the placebo group. Itch-related quality of life also improved more on the drug. It was measured on the 5-D itch and Skindex-10 scales. 1
The label pools KALM-1 with the similar KALM-2 trial, giving 424 patients per arm. Across both, the drug's advantage over placebo held. The FDA approved it on that basis. The placebo response was large, which is typical for itch trials. So the absolute gain is roughly one extra responder for every five patients treated. 12
| Study | Model | Finding |
|---|---|---|
| KALM-1 | Humans, n=378, randomized double-blind placebo-controlled, 12 weeks | 52% of patients on difelikefalin had at least a 3-point drop in weekly itch score versus 31% on placebo. 1 |
| Pooled KALM-1 and KALM-2 (label) | Humans, n=848, two randomized placebo-controlled trials | The itch benefit held across both trials and the adverse event profile was dominated by diarrhea, dizziness and nausea. 2 |
Safety
The pooled trials reported several adverse events more often with difelikefalin than with placebo. The most frequent were diarrhea (9.0% versus 5.7% on placebo), dizziness (6.8% versus 3.8%), nausea (6.6% versus 4.5%) and gait disturbance including falls (6.6% versus 5.4%). Hyperkalemia, headache, somnolence and mental status change were also more common than on placebo. Somnolence was more common in patients 65 and older. The label warns about dizziness, sleepiness, mental status changes and gait problems. It also warns about added effects with other sedating drugs. Dizziness was the most common reason for stopping. 2
Less is known about long-term safety beyond the one-year open-label extensions. Less is known about safety in people with normal kidney function. The trial group was entirely on dialysis. 12
Questions for your clinician
- Is there evidence for itch in people who are not on dialysis?
- How would dizziness and falls be managed?
- Does it add to the effect of other sedating medicines I take?
Questions people ask
Is difelikefalin FDA-approved?
Yes. Korsuva (difelikefalin) was approved in 2021 for moderate-to-severe itch linked to chronic kidney disease in adults on hemodialysis. Staff give it intravenously during dialysis. Patients do not self-inject it. 2
Is difelikefalin an opioid?
It acts on the kappa-opioid receptor, so it is an opioid in pharmacology terms. It is designed not to enter the brain in meaningful amounts. That is why it does not cause the euphoria or slowed breathing of morphine-type drugs. It is not scheduled as a controlled substance. 12
Does difelikefalin work for itch in people who are not on dialysis?
That has not been established. The approval and the trials cited here cover hemodialysis patients only. The manufacturer has run trials of an oral form in other itch conditions. None has led to an approved use as of October 2026. 2
Which adverse events occurred more often than with placebo?
Diarrhea, dizziness, nausea and gait disturbance were the commonest events reported more often than placebo in the pooled trials. Hyperkalemia, headache, somnolence and mental status change followed. Sleepiness was more frequent in older patients. 2