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Difelikefalin (Korsuva)_Dosage, benefits & legal status

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

Published October 14, 2026

A kappa-opioid peptide built from D-amino acids so it stays out of the brain, given into the dialysis line three times a week.

Relieve kidney-disease itchPeripheral kappa-opioid agonist (D-peptide)FDA-approved
Dose0.5 mcg/kg after each dialysis session (label)
FrequencyThree times a week, at the end of haemodialysis
RouteInto a vein, through the dialysis line
StatusFDA-approved
CycledContinuous, with each dialysis session

Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.

See how this dose compares across the library →

01

What is Difelikefalin (Korsuva)?

Plain language first. The technical label stays, but it never stands alone.

Overview

Many people on kidney dialysis suffer constant, severe itching. Given into the dialysis line after each session, difelikefalin cut itch by at least 4 points on a 10-point scale in 37 to 40% of patients, against 21 to 26% on placebo. The FDA approved it in 2021, and it is not a controlled substance. Oral versions failed in other kinds of itch.

The technical version

Difelikefalin is four D-amino acids (D-Phe-D-Phe-D-Leu-D-Lys) capped with a ring-shaped amino acid, 4-aminopiperidine-4-carboxylic acid. It activates kappa-opioid receptors on nerve endings and immune cells outside the brain and shows little or no activity at the mu-opioid receptor that morphine targets. Cara Therapeutics discovered it; CSL Vifor now holds the rights; Cara itself completed a reverse merger with Tvardi Therapeutics in April 2025 and took the Tvardi name.

What it's used for

A prescription injection for moderate to severe itch caused by chronic kidney disease in adults on haemodialysis, given by dialysis staff.

02

How does Difelikefalin (Korsuva) work?

What it does in the body, and where.

Difelikefalin switches on kappa-opioid receptors outside the brain to damp itch without the effects of morphine-type opioids.

  1. 01
    Where it works
    Kappa-opioid receptors sit on sensory nerve endings and immune cells in the skin. Activating them quietens itch signals and reduces the release of nerve-sensitising inflammatory chemicals. The label notes the exact link to its benefit is not known.
  2. 02
    Kept out of the brain
    Its mirror-image amino acids resist enzymes, and its charged, water-loving structure keeps it out of the brain; levels there were below the limit of measurement. In lab tests it barely touches the mu-opioid receptor.
  3. 03
    Why three times a week
    Healthy kidneys clear it within hours. In people on dialysis the half-life stretches to about a day, so one dose after each session covers the gap; dialysis itself removes 70 to 80%.
Pathway
THE PEPTIDE
Difelikefalin (Korsuva)
ACTS ON
Kappa-opioid receptors on nerve endings and immune cells outside the brain
RESULT
Itch signals from the skin are dampened
RESULT
Little or no mu-opioid activity, and very little reaches the brain

A schematic of the compound's mechanism, not a diagnostic image.

03

What else is it used for?

Each group carries its own evidence level.

Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.

Dialysis itch

FDA-approved
  • Human trialKALM-1, 378 patients: at least 3-point improvement in 49.1% against 27.9%, with better itch-related quality of life.
  • Human trialKALM-2, 473 patients: 54.0% against 42.2%; the Skindex-10 quality-of-life score did not differ significantly (p=0.171).
  • Human trialA Chinese phase 3 in 260 patients also showed a larger itch reduction at week 4.
Study
Topf J et al., Kidney Medicine 2022 (pooled KALM-1 and KALM-2); China phase 3 posted results (NCT05885737)

Oral version: notalgia paraesthetica

tested-and-failed
  • Human trialA 126-person phase 2 was positive, but the 214-person KOURAGE-1 showed no meaningful benefit at any dose, and the programme ended in 2024.
Study
Cara Therapeutics 8-K (Jun 2024)

Oral version: atopic dermatitis

tested-and-failed
  • Human trialKIND-1 showed no meaningful benefit over topical steroids alone, and the programme stopped in December 2023.
Often left out

The trials' primary endpoint was at least a 3-point improvement, but the US label reports the 4-point result (40% against 21%; 37% against 26%), so the two sets of figures are not interchangeable. KALM-1's 3-point result is quoted as 49.1%, 51.0% or 51.9% depending on how missing data were handled. Its half-life is not '2 hours' in the people who use it: that is healthy volunteers; on dialysis it is 23 to 31 hours. The US label counts all-cause side effects (dizziness 6.8%) and the EU label only drug-related ones (0.9%). The advanced kidney disease trials were stopped, not failed. It ends in a free acid, not an amide, despite the patent title. Australia sells it as Korsuva, not Kapruvia. Cara sold the rights to CSL Vifor for $0.9 million while paying it $3 million.

Study
Cara Therapeutics 8-K (Dec 2023)

The published record

Research index

155

Papers and trials about Difelikefalin (Korsuva)

96 papers tagged human · 48 not reviews or lab · 16 clinical trial publications

28 registered trials · 12 with posted results

Furthest stage reached: Approved in the US

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In animals16
In the lab0
Reviews33
Senior author shareSpread across many groups

Evidence summary

Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.

Difelikefalin (Korsuva) vial rendering
Compound field notes

At a glance

Four things to know about Difelikefalin (Korsuva)

01

Evidence

FDA-approved

02

Category

Healing and recovery

03

Common vial

Varies

04

Half-life

23 to 31 hours in dialysis patients (2 to 3 hours in healthy people)

04

How much, and do you cycle it?

The range, and whether you take breaks.

0.5 mcg/kg after each dialysis session (label), three times a week, at the end of haemodialysis. Continuous, with each dialysis session FDA label

Given after every haemodialysis session for as long as the itch needs treating; the trials ran 12 weeks double-blind with a 52-week open-label extension.

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05

How long does it stay in the body?

The half-life, and where the figure comes from.

23 to 31 hours in dialysis patients (2 to 3 hours in healthy people)FDA label

With working kidneys most of a dose leaves in the urine within hours. On dialysis it is cleared mainly in faeces and dialysate, and one dialysis session removes 70 to 80%. It is barely metabolised and not handled by liver CYP enzymes.

Source: Korsuva prescribing information section 12.3; Kapruvia SmPC section 5.2

You can compare this against the whole library to see where it sits.

06

How is it given?

Dosing context and source notes.
No draw available

0.5 micrograms per kg of target dry body weight, as an intravenous bolus into the venous line at the end of each haemodialysis session, usually three times a week. The volume in mL is the dry weight in kg times 0.01. A missed dose is given at the end of the next session. In the EU, patients of 195 kg and over get a fixed 100 micrograms, and no more than 4 doses a week. Given by dialysis staff; the vial calculator does not apply.

07

How do you store it?

Before mixing, and after.

Dry powder in the freezer or fridge. Once mixed, fridge, and use within about a month.

Unmixed lyophilized Difelikefalin (Korsuva) keeps for a long time cold. Once you add water the clock starts: most reconstituted vials hold up for roughly 28 to 30 days at fridge temperature. Keep it out of light, and do not freeze it after mixing.

08

What are the side effects and cautions?

Known cautions and warnings for this compound.

Solubility, computed: 60% charged residues, 80% hydrophobic. Water usually sufficient.

A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.

Who should avoid it

Check these before anything else.
  • Peritoneal dialysis: not studied and not recommended
  • Severe liver impairment: not recommended (US label)
  • Use outside haemodialysis: it is dosed into the dialysis circuit by dialysis staff
  • Care with sedatives, sedating antihistamines and opioids: they add to dizziness and sleepiness

Stop and get help

These are emergencies. Seek care.
  • Confusion, severe drowsiness or a fall
  • Swelling of the face or throat, or trouble breathing

Common effects

Expected, and usually mild.
  • Diarrhoea in 9.0% against 5.7% on placebo
  • Dizziness in 6.8% against 3.8%, and nausea in 6.6% against 4.5%
  • Unsteadiness including falls in 6.6% against 5.4%; sleepiness in 4.2% against 2.4%, more in people over 65
  • High potassium in 4.7% against 3.5%
  • Stopping because of side effects: 2.6% against 0.7%

Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.

09

Is Difelikefalin (Korsuva) approved?

And where the numbers on this page come from.

Yes. Difelikefalin (Korsuva) is FDA approved and available on prescription in the United States. It is also approved in the European Union, the United Kingdom, Switzerland, Australia, and Japan.

What has happened recently

FDA-approved on 23 August 2021 (NDA 214916, priority review) for moderate to severe itch associated with chronic kidney disease in adults on haemodialysis; not for peritoneal dialysis. It is not a federally controlled substance. The EU authorised it as Kapruvia on 25 April 2022, followed by Great Britain (2022), Switzerland (2022), Australia (2022, as Korsuva) and Japan (2023); NICE recommends it for in-centre haemodialysis. Before Cara Therapeutics completed a reverse merger with Tvardi Therapeutics on 15 April 2025, taking the Tvardi name, it sold the Korsuva and Kapruvia rights to CSL Vifor, now the holder of the US application. No generic has been approved.

You can compare this against the whole library, or read how to check a seller.

10

What else is like Difelikefalin (Korsuva)?

Others in Healing and recovery, side by side.

If you're weighing Difelikefalin (Korsuva), it's worth reading PDA (Pentadeca Arginate), GLOW blend, and KLOW blend in the same class.

YOU ARE HERE
Difelikefalin (Korsuva)

A kappa-opioid peptide built from D-amino acids so it stays out of the brain, given into the dialysis line three times a week.

FDA-approved
Dose
0.5 mcg/kg after each dialysis session (label)
How often
Three times a week, at the end of haemodialysis
PDA
PDA (Pentadeca Arginate)

A newer, more stable cousin of BPC-157 for faster healing.

Research only
Dose
0.25 up to 0.5 mg per day (start low, increase slowly)
How often
1-2x daily
GLOW
GLOW blend

A popular skin-and-healing blend of three peptides in one shot.

Research only
Dose
Community examples use 2 to 2.5 mg of total blend per day, or set the draw by GHK-Cu.
How often
Daily
KLOW
KLOW blend

The GLOW blend plus an anti-inflammatory peptide, an all-in-one recovery stack.

Research only
Dose
Community examples use 2 to 4 mg of total blend per day, or set the draw by GHK-Cu.
How often
Daily

Guides for this compound

Sources

Beyond these, 155 records are indexed. Browse the records