Skin & aging Kappa-opioid agonist peptide
Difelikefalin
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- FDA approval
- An FDA-approved product contains this peptide
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Difelikefalin (sold as Korsuva) is a peptide that activates kappa-opioid receptors to relieve the intense itching that affects many people on dialysis. Because it barely enters the brain, it eases itch without the typical opioid effects on mood or breathing. It has been FDA-approved in the U.S. since 2021 and is given intravenously during hemodialysis.
At a glance
- What it is
- A peripherally restricted kappa-opioid receptor agonist peptide
- Approved for
- Moderate-to-severe itching associated with chronic kidney disease in adults on hemodialysis
- Key fact
- In the KALM-1 trial, more patients on difelikefalin than placebo had a meaningful reduction in itch
- Route
- Intravenous, into the dialysis circuit at the end of each session
- Evidence strength
- FDA approved
Summary
Difelikefalin (Korsuva) is an FDA-approved peptide for itch in adults on hemodialysis. Learn how it works, what the trials showed, and its side effects.
What is difelikefalin?
Difelikefalin, sold under the brand Korsuva, is a synthetic peptide made of D-amino acids that activates kappa-opioid receptors. It is used for the persistent, often severe itch (pruritus) that affects many people with advanced kidney disease on hemodialysis, a symptom that is hard to treat and badly affects quality of life. Because it is a water-loving peptide that does not readily cross into the brain, it acts largely outside the central nervous system. It was developed under the codes CR845 and FE 202845 and approved in the United States in 2021.
How does difelikefalin work?
Difelikefalin selectively activates kappa-opioid receptors, which are found on peripheral sensory nerves and on immune cells. The table below shows what activating each set of receptors does.
| Where the kappa receptors sit | Effect of activating them |
|---|---|
| Itch-sensing peripheral sensory nerves | Dampens the transmission of itch signals |
| Immune cells | May reduce the release of itch-promoting and inflammatory mediators |
The net effect is reduced itch.
Its design is central to its profile: as a peripherally restricted peptide, it reaches these peripheral kappa receptors but has minimal entry into the brain, so it avoids the euphoria, dependence, and respiratory depression associated with classic opioids that act on mu receptors. In the KALM-1 trial, a significantly larger share of patients on difelikefalin than on placebo achieved a meaningful improvement in itch intensity over 12 weeks, with better itch-related quality of life.
Is it FDA-approved?
Editor’s note
Status: Yes. Difelikefalin was approved by the FDA in 2021 for moderate-to-severe pruritus associated with chronic kidney disease in adults on hemodialysis. It is given as an intravenous bolus into the venous line of the dialysis circuit at the end of each session, three times a week.
Category: FDA-approved · Primary body area: Skin & aging
Yes. Difelikefalin was approved by the FDA in 2021 for moderate-to-severe pruritus associated with chronic kidney disease in adults on hemodialysis. It is given as an intravenous bolus into the venous line of the dialysis circuit at the end of each session, three times a week.
What is difelikefalin prescribed for?
Difelikefalin is prescribed for the itch of chronic kidney disease in adults undergoing hemodialysis. It is not a general anti-itch drug and is tied to the dialysis setting, which makes its intravenous dosing practical.
What are the side effects?
According to the prescribing information, common side effects include:
- Diarrhea
- Dizziness and nausea
- High potassium
- Headache
More serious considerations include:
- Dizziness, drowsiness, and changes in mental status or gait, which can raise the risk of falls, especially with sedating medicines
- Caution when combined with other central nervous system depressants
Sources: FDA prescribing information for Korsuva; the KALM-1 trial (Fishbane et al., The New England Journal of Medicine, 2020, DOI: 10.1056/NEJMoa1912770), indexed on PubMed. This document is educational and does not constitute medical advice.
Registered human trials
0 registered human trials on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
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