Peptides / Skin and hair

Synthetic analog · 5 amino acids · 679.8 Da

Difelikefalin

ApprovedNot banned in sport

Difelikefalin (Korsuva, Kapruvia) is a peptide kappa opioid receptor agonist approved in the US and EU for itch in adults with kidney disease on hemodialysis. Studies in people tested it mostly on itch and quality of life, and tracked side effects. PepBank shows 247 results on difelikefalin from 34 studies in people, and 23 from animal and lab studies. The strongest evidence is a randomized trial in people. Data as of 2026-10-30.

Also known as CR-845, CR845, Kapruvia, Korsuva

5 amino acids, from first to lastFFLKX

Evidence level: Large trials in people247 of 272 results come from studies in people, including randomized trials.

Results in people

247

91% of 272 results

Results in animals

7% of 272 results

Results in lab cells

1% of 272 results

From computer models

under 1% of 272 results

Overview

Difelikefalin at a glance

What it is	Synthetic analog, 5 amino acids
Approval	Approved in the US and EU (Korsuva, 2021)
In sport	Not listed as banned by WADA
Studies	41 studies with results. 40 of them gave difelikefalin, with 272 results. 247 in people20 in animals3 in lab cells2 from computer models
Best study in people	Randomized controlled trial with 323 people (2020)
Clinical trials	28 registered: 2 active or planned, 12 with posted results
Community use	Moderate to severe CKD-associated pruritus in adults receiving hemodialysis

The science

What is difelikefalin?

Difelikefalin is a synthetic peptide kappa opioid receptor agonist.

Amino acids in one chain

The history of difelikefalin

2015September
A registered trial of difelikefalin started (NCT02542384).
2020
The oldest paper on difelikefalin in PepBank is from 2020.
2021August
FDA approved Korsuva for moderate to severe CKD-associated pruritus in adults receiving hemodialysis.

Difelikefalin structure and chemistry

The key facts about the molecule. Long codes are in the closed section below.

Sequence, 5 amino acidsFrom the first amino acid to the last

F1FL+KX5

Darker means more water-repelling+ and − show charge in the bodyOutlined: changed amino acid

Structure

Difelikefalin is a synthetic analog of 5 amino acids, with no ring, 5 changed amino acids.

Formula

C₃₆H₅₃N₇O₆

Molecular weight

679.8 g/mol

CAS number

1024828-77-0

Target

Kappa opioid receptor (gene OPRK1): agonistEvidence: Official prescribing information, mechanism of action

Development

Highest phase: past the trial stage (see status).

Identifiers

PubChem 24794466, ChEMBL CHEMBL3989915, UNII NA1U919MRO, DrugBank DB11938

Full sequence, SMILES and InChIKey

Three-letter sequence
D-Phe-D-Phe-D-Leu-D-Lys-(4-amino-piperidine-4-carboxylic acid)

InChIKey
FWMNVWWHGCHHJJ-SKKKGAJSSA-N

SMILES
CC(C)C[C@H](C(=O)N[C@H](CCCCN)C(=O)N1CCC(CC1)(C(=O)O)N)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](CC3=CC=CC=C3)N

See charge, composition and 3D structure on the Scientific page

The evidence

What difelikefalin studies show

Results grouped by what the studies measured. Each card shows where its results come from.

Large trials in people247 of 272 results come from studies in people, including randomized trials.

Skin, hair and wounds

69 results · 66 in people · 2 animal · 1 lab

In hemodialysis patients, difelikefalin reduced itch more than placebo at week 4. NEJM evidence, 2023

Top results

In hemodialysis patients, difelikefalin reduced itch more than placebo at week 4. (NEJM evidence, 2023)
In hemodialysis patients, difelikefalin produced more itch responses than placebo. (The New England journal of medicine, 2020)
In Japanese hemodialysis patients, itch score changes were -2.97 with difelikefalin 0.25 μg/kg versus -2.86 with placebo. (JAMA network open, 2022)

Daily life and fitness

19 results · 19 in people

Difelikefalin secondary results generally did not support the primary benefit versus placebo. The New England journal of medicine, 2023

Top results

Difelikefalin secondary results generally did not support the primary benefit versus placebo. (The New England journal of medicine, 2023)
In hemodialysis patients, difelikefalin improved itch-related quality of life on Skindex-10 more than placebo. (Kidney international reports, 2020)
In hemodialysis patients receiving difelikefalin, mental quality of life scores did not change significantly compared with baseline. (International urology and nephrology, 2026)

Sleep

9 results · 9 in people

In hemodialysis patients, sleep reports were similar after stopping or continuing difelikefalin. Clinical and translational science, 2023

Top results

In hemodialysis patients, sleep reports were similar after stopping or continuing difelikefalin. (Clinical and translational science, 2023)
In hemodialysis patients, difelikefalin improved sleep disturbance more than placebo. (Kidney international reports, 2020)
In hemodialysis patients receiving difelikefalin, 66% reported sleep quality improvement of at least 3 points. (Kidney medicine, 2022)

Survival and serious illness

7 results · 6 in people · 1 animal

In hemodialysis patients, deaths occurred in 0.7% with difelikefalin versus 1.2% with placebo. Kidney medicine, 2022

Top results

In hemodialysis patients, deaths occurred in 0.7% with difelikefalin versus 1.2% with placebo. (Kidney medicine, 2022)
Three hemodialysis patients (15%) died from unrelated cardiovascular events during difelikefalin treatment. (International urology and nephrology, 2026)
In hemodialysis patients receiving difelikefalin, no deaths were considered treatment-related. (Kidney medicine, 2022)

Immune system and inflammation

9 results · 4 in people · 3 animal · 1 lab

In patients with kidney disease-related itching, combined reductions in ten markers differed significantly between difelikefalin and placebo. The Journal of investigative dermatology, 2026

Top results

In patients with kidney disease-related itching, combined reductions in ten markers differed significantly between difelikefalin and placebo. (The Journal of investigative dermatology, 2026)
In subjects with dermatitis, difelikefalin reduced expression of the dermatitis-associated gene CCL17. (The Journal of allergy and clinical immunology, 2023)
In subjects with dermatitis, difelikefalin reduced TH2 pathway activity, whereas placebo did not. (The Journal of allergy and clinical immunology, 2023)

Kidneys and bladder

12 results · 12 animal

In rats, difelikefalin significantly increased urine output. Pharmacological research, 2022

Top results

In rats, difelikefalin significantly increased urine output. (Pharmacological research, 2022)
In mice with critical illness, difelikefalin reduced acute kidney injury. (PloS one, 2026)
In rats with kidney injury, difelikefalin improved blood urea nitrogen levels. (BMC nephrology, 2025)

All 41 difelikefalin studies by area Open the Scientific page

Key difelikefalin studies

Studies in people come first, then studies in animals and in the lab.

People
A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus
Fishbane et al. 2020 · The New England journal of medicine · 323 people · cited by 267
8 results
People
Difelikefalin for Hemodialysis Patients with Pruritus in Japan
Narita et al. 2023 · NEJM evidence · 178 people · cited by 6
4 results
People
Randomized Controlled Trial of Difelikefalin for Chronic Pruritus in Hemodialysis Patients
Fishbane et al. 2020 · Kidney international reports · 174 people · cited by 75
10 results
People
Evaluation of the abuse potential of difelikefalin, a selective kappa-opioid receptor agonist, in recreational polydrug users
Shram et al. 2022 · Clinical and translational science · 44 people · cited by 24
14 results
People
Assessment of the physical dependence potential of difelikefalin: Randomized placebo-controlled study in patients receiving hemodialysis
Spencer et al. 2023 · Clinical and translational science · 30 people · cited by 8
4 results

All 41 Difelikefalin studies

Difelikefalin clinical trials

ClinicalTrials.gov lists 28 trials of difelikefalin. 2 are active or planned, and 12 have posted results. PepBank does not show trial results.

Solid bars are dates that happened. Hatched bars are planned dates. Data from ClinicalTrials.gov.

CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

Phase 3completed473 people

A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)

Phase 3completed378 people

Extension Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

Phase 3completed288 people

All 15 Difelikefalin trials

Status and safety

Is difelikefalin approved?

FDA

United States

Approved

An approved medicine contains it.

EMA

European Union

Approved

An approved medicine contains it.

WADA

Sport

Not banned

Not on the 2026 Prohibited List.

Yes. Approved in the US and EU (Korsuva, 2021). The FDA label for Korsuva says: “Moderate to severe CKD-associated pruritus in adults receiving hemodialysis” Not listed as banned by WADA.

Laws and labels change, so check the regulator for the current status.

Difelikefalin side effects and safety

PepBank has 123 safety results from studies of difelikefalin. 123 of them come from studies in people.

Safety results from studies (123)

In recreational polydrug users, peak drug liking was significantly lower with difelikefalin than pentazocine. (Clinical and translational science, 2022)
In hemodialysis patients, withdrawal scores were similar after stopping or continuing difelikefalin. (Clinical and translational science, 2023)
In healthy volunteers, neither difelikefalin nor placebo caused carbon dioxide increases that met the respiratory-depression criterion. (Clinical and translational science, 2021)
In hemodialysis patients, diarrhea occurred more often with difelikefalin than placebo. (The New England journal of medicine, 2020)
Black/AA patients receiving difelikefalin had more treatment-emergent adverse events than those receiving placebo. (American journal of nephrology, 2024)
In hemodialysis patients, diarrhea occurred in 9.0% with difelikefalin versus 5.7% with placebo. (Kidney medicine, 2022)
In hemodialysis patients, treatment-related adverse events occurred in 15% with difelikefalin versus 3% with placebo. (NEJM evidence, 2023)
In hemodialysis patients, adverse events occurred more often with difelikefalin than placebo. (Kidney international reports, 2020)
In Japanese hemodialysis patients, adverse events occurred in 72% with difelikefalin 0.25 μg/kg versus 67% with placebo. (JAMA network open, 2022)
Patients receiving difelikefalin had more headaches than those receiving placebo. (The New England journal of medicine, 2023)
In hemodialysis patients, treatment-related adverse events with difelikefalin occurred in 16 participants (7.2%). (Kidney medicine, 2022)
In adults on haemodialysis receiving difelikefalin, no treatment-related deaths occurred. (Journal of renal care, 2025)
In adolescents on haemodialysis, one participant developed mild headache related to difelikefalin treatment. (Pediatric nephrology, 2026)
Dizziness was a common adverse event during difelikefalin treatment. (Journal of the American Academy of Dermatology, 2023)
Safety findings matched the known difelikefalin profile across the study groups. (BMC nephrology, 2024)
In Chinese haemodialysis patients receiving difelikefalin, most adverse events were mild or moderate. (Clinical kidney journal, 2026)
Among difelikefalin recipients, serious nonfatal adverse events were more common with opioid use than without, and the same pattern appeared with placebo. (Kidney & blood pressure research, 2026)
Among difelikefalin recipients, 38.1% experienced adverse events. (Clinical kidney journal, 2025)
Eight hemodialysis patients (40%) discontinued difelikefalin treatment. (International urology and nephrology, 2026)
One patient receiving difelikefalin stopped treatment because of dizziness. (Clinical kidney journal, 2025)
Four difelikefalin recipients reported mild to moderate adverse reactions. (Nephrologie & therapeutique, 2024)
Difelikefalin FAERS reports included other serious outcomes. These reports do not establish causation. (Nephrology, dialysis, transplantation, 2026)
In a patient receiving difelikefalin for kidney disease-related itching, brief vertigo occurred when treatment began. (Case reports in nephrology, 2025)
In a haemodialysis patient, difelikefalin caused drowsiness that disappeared when treatment stopped temporarily. (Ugeskrift for laeger, 2025)

See every safety result on the Scientific page

Doses studied (33 shown)

The doses that these studies used. They are not recommendations.

Dose as reported	Class	Species	Route	Duration	Design	Source
0.5 μg/kg three times per week	Human	human	intravenous	12 weeks	Randomized trial in people · n = 323	Fishbane 2020
0.5 μg/kg three times per week	Human	human	intravenous	6 weeks	Randomized trial in people · n = 178	Narita 2023
0.5, 1.0, or 1.5 μg/kg thrice weekly	Human	human	intravenous	8 weeks	Randomized trial in people · n = 174	Fishbane 2020
5 and 15 mcg/kg	Human	human	intravenous	single injection	Randomized trial in people · n = 44	Shram 2022
1.0 and 5.0 mcg/kg	Human	human	intravenous	Not reported	Randomized trial in people · n = 15	Viscusi 2021
0.25 μg/kg three times a week	Human	human	intravenous	8 weeks	Randomized trial in people	Narita 2022
0.5 μg/kg three times a week	Human	human	intravenous	8 weeks	Randomized trial in people	Narita 2022
1.0 μg/kg three times a week	Human	human	intravenous	8 weeks	Randomized trial in people	Narita 2022
1.0 mg once daily	Human	human	oral	12 weeks	Randomized trial in people	Yosipovitch 2023
0.25 mg once daily	Human	human	oral	12 weeks	Randomized trial in people	Yosipovitch 2023
0.5 mg once daily	Human	human	oral	12 weeks	Randomized trial in people	Yosipovitch 2023
2 mg twice daily	Human	human	oral	8 weeks	Randomized trial in people	Kim 2023
0.5 µg/kg	Human	human	intravenous	12 weeks	Randomized trial in people · n = 249	Fishbane 2024
0.5 mcg/kg three times/wk	Human	human	intravenous	12 weeks	Randomized trial in people · n = 851	Topf 2022
0.5 mcg/kg	Human	human	intravenous	Not reported	Randomized trial in people · n = 848	Fishbane 2022
0.5 μg/kg after each hemodialysis session	Human	human	intravenous	12 weeks	Trial in people without random groups · n = 222	Weiner 2022
0.5 µg/kg	Human	human	Not reported	12 weeks	Trial in people without random groups · n = 222	McCafferty 2025
0.5 µg/kg	Human	human	Not reported	12 weeks	Trial in people without random groups	Burton 2026
0.25 mg	Human	human	oral	12 weeks	Trial in people without random groups · n = 401	Guttman-Yassky 2023
0.5 mg	Human	human	oral	12 weeks	Trial in people without random groups · n = 401	Guttman-Yassky 2023
1.0 mg	Human	human	oral	12 weeks	Trial in people without random groups · n = 401	Guttman-Yassky 2023
3.0 mcg/kg	Human	human	intravenous	single dose	Trial in people without random groups · n = 36	Spencer 2024
0.5, 1.0, or 2.5 mcg/kg	Human	human	intravenous	3 doses over 1 week	Trial in people without random groups · n = 19	Spencer 2024
1.7-3.0 μg/kg	Human	human	intravenous	single dose	Trial in people without random groups · n = 12	Stark 2023
0.5 μg/kg dry body weight	Human	human	intravenous bolus	single dose	Trial in people without random groups · n = 8	Mourani 2026
0.25, 0.5, and 1.0 μg/kg three times a week	Human	human	intravenous	8 weeks	Trial in people without random groups	Narita 2022
0.5 µg/kg after each HD session	Human	human	intravenous	median 115 days (min-max 30-1035)	Observational study · n = 438	Latus 2025
0.5 mcg/kg after each HD session	Human	human	intravenous	up to 12 months	Observational study · n = 20	Di 2026
0.5 µg/kg three times weekly	Human	human	intravenous	12 weeks	Observational study	Weiner 2024
50 μg × 3/week	Human	human	Not reported	three weeks	Reports of single patients · n = 1	Larsen 2025
25 μg × 3/week	Human	human	Not reported	Not reported	Reports of single patients · n = 1	Larsen 2025
1.0 mg/kg	Animal	mouse	intraperitoneal	single injection	Study in live animals	Tamari 2023
0.5 mg/kg twice daily	Animal	mouse	intraperitoneal	Not reported	Study in live animals	Tamari 2023

From the community

How people use it

What people report online. It comes from forums and guides, not from studies.

Community-reported. Not tested in trials.

The US label covers Korsuva injection for adults with moderate-to-severe CKD-associated pruritus undergoing hemodialysis. This record describes one label regimen.

Reported routines and cautions

What people use it for

Moderate to severe CKD-associated pruritus in adults receiving hemodialysisS1

Reported regimens

Regimens that community sources report for Difelikefalin. Community-reported, not tested in trials.
Context	Route	Amount	How often	How long	Agreement	Sources
Korsuva injection, 65 mcg/1.3 mL (50 mcg/mL), for moderate-to-severe CKD-associated pruritus in adults undergoing hemodialysisOfficial label dosing of an approved product	intravenous bolus injectionThe label specifies the venous line of the dialysis circuit, after blood no longer circulates through the dialyzer.	0.5 mcg/kg per dose	at the end of each hemodialysis treatment	Not stated	Single official US label source.	S1

Cautions

The label warns about dizziness, somnolence, mental status changes and gait disturbances, including falls. Centrally acting depressants, sedating antihistamines and opioid analgesics require caution. Driving or dangerous machinery requires knowledge of the individual drug effect. Use in severe hepatic impairment is not recommended.S1

Status notes

EMA reports EU authorisation of Kapruvia for moderate-to-severe CKD-associated pruritus in adults on haemodialysis.S2

Community sources

S1Korsuva US prescribing information (opens in a new tab)dailymed.nlm.nih.gov
S2EMA regulatory information (opens in a new tab)ema.europa.eu

Gaps

This review establishes one selected US label regimen. It does not establish a separate non-vendor community regimen or an exhaustive community search. The record does not replace the full label.

Questions and more

Ask a question about difelikefalin

The answer links to every study it uses.

What does the evidence say about difelikefalin?Is difelikefalin tested in people?Compare with L-carnosine Compare with Argireline (acetyl hexapeptide-8)

Sources

Database: PepBank data for difelikefalin (data version 308560)
Regulator: FDA status record
Regulator: EMA status record
Regulator: WADA status record
Trial registry: ClinicalTrials.gov
Community: community sources (forums and guides), as summarized in the PepBank community file

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

PepBank is a research reference. Talk to a doctor before you use any peptide.

Ask your AI about difelikefalin

Difelikefalin

ApprovedNot banned in sport

Also known as CR-845, CR845, Kapruvia, Korsuva

What it is

Synthetic analog, 5 amino acids

Approval

Approved in the US and EU (Korsuva, 2021)

In sport

Not listed as banned by WADA

Studies

41 studies with results. 40 of them gave difelikefalin, with 272 results.
247 in people20 in animals3 in lab cells2 from computer models

Best study in people

Randomized controlled trial with 323 people (2020)

Clinical trials

28 registered: 2 active or planned, 12 with posted results

Community use

Moderate to severe CKD-associated pruritus in adults receiving hemodialysis

Dose as reported

Class

Species

Route

Duration

Design

Source

0.5 μg/kg three times per week

Human

human

intravenous

12 weeks

Randomized trial in people · n = 323

Fishbane 2020

0.5 μg/kg three times per week

Human

human

intravenous

6 weeks

Randomized trial in people · n = 178

Narita 2023

0.5, 1.0, or 1.5 μg/kg thrice weekly

Human

human

intravenous

8 weeks

Randomized trial in people · n = 174

Fishbane 2020

5 and 15 mcg/kg

Human

human

intravenous

single injection

Randomized trial in people · n = 44

Shram 2022

1.0 and 5.0 mcg/kg

Human

human

intravenous

Not reported

Randomized trial in people · n = 15

Viscusi 2021

0.25 μg/kg three times a week

Human

human

intravenous

8 weeks

Randomized trial in people

Narita 2022

0.5 μg/kg three times a week

Human

human

intravenous

8 weeks

Randomized trial in people

Narita 2022

1.0 μg/kg three times a week

Human

human

intravenous

8 weeks

Randomized trial in people

Narita 2022

1.0 mg once daily

Human

human

oral

12 weeks

Randomized trial in people

Yosipovitch 2023

0.25 mg once daily

Human

human

oral

12 weeks

Randomized trial in people

Yosipovitch 2023

0.5 mg once daily

Human

human

oral

12 weeks

Randomized trial in people

Yosipovitch 2023

2 mg twice daily

Human

human

oral

8 weeks

Randomized trial in people

Kim 2023

0.5 µg/kg

Human

human

intravenous

12 weeks

Randomized trial in people · n = 249

Fishbane 2024

0.5 mcg/kg three times/wk

Human

human

intravenous

12 weeks

Randomized trial in people · n = 851

Topf 2022

0.5 mcg/kg

Human

human

intravenous

Not reported

Randomized trial in people · n = 848

Fishbane 2022

0.5 μg/kg after each hemodialysis session

Human

human

intravenous

12 weeks

Trial in people without random groups · n = 222

Weiner 2022

0.5 µg/kg

Human

human

Not reported

12 weeks

Trial in people without random groups · n = 222

McCafferty 2025

0.5 µg/kg

Human

human

Not reported

12 weeks

Trial in people without random groups

Burton 2026

0.25 mg

Human

human

oral

12 weeks

Trial in people without random groups · n = 401

Guttman-Yassky 2023

0.5 mg

Human

human

oral

12 weeks

Trial in people without random groups · n = 401

Guttman-Yassky 2023

1.0 mg

Human

human

oral

12 weeks

Trial in people without random groups · n = 401

Guttman-Yassky 2023

3.0 mcg/kg

Human

human

intravenous

single dose

Trial in people without random groups · n = 36

Spencer 2024

0.5, 1.0, or 2.5 mcg/kg

Human

human

intravenous

3 doses over 1 week

Trial in people without random groups · n = 19

Spencer 2024

1.7-3.0 μg/kg

Human

human

intravenous

single dose

Trial in people without random groups · n = 12

Stark 2023

0.5 μg/kg dry body weight

Human

human

intravenous bolus

single dose

Trial in people without random groups · n = 8

Mourani 2026

0.25, 0.5, and 1.0 μg/kg three times a week

Human

human

intravenous

8 weeks

Trial in people without random groups

Narita 2022

0.5 µg/kg after each HD session

Human

human

intravenous

median 115 days (min-max 30-1035)

Observational study · n = 438

Latus 2025

0.5 mcg/kg after each HD session

Human

human

intravenous

up to 12 months

Observational study · n = 20

Di 2026

0.5 µg/kg three times weekly

Human

human

intravenous

12 weeks

Observational study

Weiner 2024

50 μg × 3/week

Human

human

Not reported

three weeks

Reports of single patients · n = 1

Larsen 2025

25 μg × 3/week

Human

human

Not reported

Reports of single patients · n = 1

Larsen 2025

1.0 mg/kg

Animal

mouse

intraperitoneal

single injection

Study in live animals

Tamari 2023

0.5 mg/kg twice daily

Animal

mouse

intraperitoneal

Not reported

Study in live animals

Tamari 2023

Context

Route

Amount

How often

How long

Agreement

Sources

Korsuva injection, 65 mcg/1.3 mL (50 mcg/mL), for moderate-to-severe CKD-associated pruritus in adults undergoing hemodialysisOfficial label dosing of an approved product

intravenous bolus injectionThe label specifies the venous line of the dialysis circuit, after blood no longer circulates through the dialyzer.

0.5 mcg/kg per dose

at the end of each hemodialysis treatment

Not stated

Single official US label source.

Difelikefalin

Difelikefalin at a glance

What is difelikefalin?

The history of difelikefalin

Difelikefalin structure and chemistry

What difelikefalin studies show

Skin, hair and wounds

Daily life and fitness

Sleep

Survival and serious illness

Immune system and inflammation

Kidneys and bladder

Key difelikefalin studies

Difelikefalin clinical trials

Is difelikefalin approved?

Difelikefalin side effects and safety

How people use it

What people use it for

Reported regimens

Cautions

Status notes

Community sources

Ask a question about difelikefalin

Related peptides

Sources

Difelikefalin

Difelikefalin at a glance

What is difelikefalin?

The history of difelikefalin

Difelikefalin structure and chemistry

What difelikefalin studies show

Skin, hair and wounds

Daily life and fitness

Sleep

Survival and serious illness

Immune system and inflammation

Kidneys and bladder

Key difelikefalin studies

Difelikefalin clinical trials

Is difelikefalin approved?

Difelikefalin side effects and safety

How people use it

What people use it for

Reported regimens

Cautions

Status notes

Community sources

Ask a question about difelikefalin

Related peptides

Sources