Difelikefalin

FDA-approved peripheral kappa opioid receptor agonistEstablished

Difelikefalin is an FDA-approved peripheral kappa opioid receptor agonist. Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists.

Calculate Dose

For research use only.

Key Facts

CAS: 1024828-77-0
Molecular Weight (MW): 679.8 g/mol
Half-life: 23–31 hours in hemodialysis patients before dialysis
FDA status: Approved
Evidence level: FDA Approved
Human dose established: Yes
Administration Route: Intravenous
Frequency: At the end of each hemodialysis treatment (three times a week in the pivotal trials)
Last updated: Nov 7, 2026
Reviewed: Nov 7, 2026

Research summary

Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis.

Research evidence

Regulatory review (FDA label)1 reviewed source
Controlled human trials1 reviewed source
Early or uncontrolled human studiesNone in reviewed sources
Lab & animal studiesNone in reviewed sources

How it works

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

Peptide Library's Difelikefalin profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.

Difelikefalin dosage evidence

Difelikefalin has an FDA-approved human dosage, as Korsuva, for moderate-to-severe itch caused by chronic kidney disease in adults on hemodialysis. The label's recommended dose is 0.5 mcg/kg given as an intravenous bolus into the venous line of the dialysis circuit at the end of each hemodialysis session.

FDA Approved

Dosage evidence summary for Difelikefalin
Human dosing established	Yes
Studied dose range	0.5 mcg/kg after each hemodialysis session (FDA label)
Route	Intravenous
Frequency	At the end of each hemodialysis treatment (three times a week in the pivotal trials)
Duration studied	Ongoing; the pivotal trials lasted 12 weeks
Half-life	23–31 hours in hemodialysis patients before dialysis
Evidence level	FDA Approved
Last reviewed	2026-11-07

Research-reported dosing

Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.

Research-reported dosing for Difelikefalin, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
FDA label — Korsuva, CKD-associated pruritusFDA-approved label · FDA prescribing information	Adults with moderate-to-severe pruritus associated with chronic kidney disease who are on hemodialysis	0.5 mcg/kg (dry body weight in the trials)	Intravenous bolus into the venous line of the dialysis circuit	At the end of each hemodialysis treatment	Ongoing; a missed dialysis session means resuming at the end of the next one	In the label's two 12-week trials, 40% and 37% had a 4-point or greater fall in worst-itch score versus 21% and 26% with placebo	KORSUVA (difelikefalin) injection — FDA prescribing information, DailyMed
KALM-1 — phase 3, NEJM 2020 (NCT03422653)Clinical trial · Randomised, double-blind, placebo-controlled phase 3 trial	Adults on hemodialysis with moderate-to-severe pruritus (n=378)	0.5 mcg/kg or placebo	Intravenous	Three times weekly	12 weeks	At least a 3-point fall in worst-itch score in 51.9% versus 30.9% with placebo (observed data); diarrhea, dizziness and vomiting were more common with difelikefalin	A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020.

Where sources disagree

Difelikefalin is a peripherally acting kappa opioid receptor agonist. The label warns about dizziness, sleepiness, mental status changes and gait problems, including falls, and advises against driving or operating machinery until its effect is known.
The label says it has not been studied in people on peritoneal dialysis and is not recommended for them. Safety and effectiveness in children have not been established.

Difelikefalin dosage in published studies and labels →

Sequence & molecular data

Sequence and molecular data for Difelikefalin
Molecular formula	C36H53N7O6
Molecular weight	679.8 g/mol
CAS number	1024828-77-0
PubChem CID	24794466
FDA UNII	NA1U919MRO
ChEMBL	CHEMBL3989915
DrugBank	DB11938

Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.

Science

Mechanism of Action

Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists.

Studies

Research statistics

101 PubMed publications · 39.4% human clinical research · 28 registered trials

Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted

Regulatory & research status

Difelikefalin is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.

Regulatory and research status for Difelikefalin
FDA status	Approved
Research status	Approved product (see FDA status)
Availability	Prescription-Only
WADA (sport)	Unknown / Not Listed
Library classification	FDA-Approved

How FDA approval, compounding and research-only status differ

Benefits

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Difelikefalin side effects

No side effects listed yet for this entry.

Storage & stability

This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.

Difelikefalin: frequently asked questions

What is Difelikefalin?

Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis.

How does Difelikefalin work?

Is Difelikefalin FDA approved?

Yes. Difelikefalin is approved by the FDA, and approved products are prescription medicines. Approval is always for specific indications studied in clinical trials, so an approved status does not mean the compound is approved for every use it is discussed for. Research-chemical material sold under the same name is not the approved product.

What peptides are similar to Difelikefalin?

Compounds most often compared with Difelikefalin include Angiotensin II, Cetrorelix, Corticorelin and Cosyntropin. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.

References

Related research, comparisons & guides

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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2

This Difelikefalin profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error

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