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Trade namesKorsuva, Kapruvia
Other namesCR845, FE-202845, D-Phe-D-Phe-D-Leu-D-Lys-[γ-(4-N-piperidinyl)amino carboxylic acid][1]
  • 4-amino-1-[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid
Clinical data
Drug classKappa opioid receptor agonist[2]
Main usesItchiness in those on hemodialysis[3]
Side effectsDiarrhea, dizziness, nausea, risk of falling, high potassium, headache, sleepiness[3]
Routes of
Typical dose0.5 mcg/kg[3]
External links
US NLMDifelikefalin
License data
Legal status
Bioavailability100% (IV)[5]
MetabolismNot metabolized[5]
Elimination half-life2 hours[5]
ExcretionExcreted as unchanged
drug via bile and urine[5]
Chemical and physical data
Molar mass679.863 g·mol−1
3D model (JSmol)
  • 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

  • as salt: CC(O)=O.CC(C)C[C@@H](NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](N)CC1=CC=CC=C1)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O
  • InChI=1S/C36H53N7O6/c1-24(2)21-29(32(45)40-28(15-9-10-18-37)34(47)43-19-16-36(39,17-20-43)35(48)49)42-33(46)30(23-26-13-7-4-8-14-26)41-31(44)27(38)22-25-11-5-3-6-12-25/h3-8,11-14,24,27-30H,9-10,15-23,37-39H2,1-2H3,(H,40,45)(H,41,44)(H,42,46)(H,48,49)/t27-,28-,29-,30-/m1/s1

  • as salt: InChI=1S/C36H53N7O6.C2H4O2/c1-24(2)21-29(32(45)40-28(15-9-10-18-37)34(47)43-19-16-36(39,17-20-43)35(48)49)42-33(46)30(23-26-13-7-4-8-14-26)41-31(44)27(38)22-25-11-5-3-6-12-25;1-2(3)4/h3-8,11-14,24,27-30H,9-10,15-23,37-39H2,1-2H3,(H,40,45)(H,41,44)(H,42,46)(H,48,49);1H3,(H,3,4)/t27-,28-,29-,30-;/m1./s1

Difelikefalin, sold under the brand name Korsuva, is a medication used to in itchiness in those on hemodialysis due to chronic kidney disease.[3] It may be used in moderate to severe cases.[6] It is given by injection into a vein at the end of dialysis.[3]

Common side effects include diarrhea, dizziness, nausea, risk of falling, high potassium, headache, and sleepiness.[3] It should not be used in people with significant liver problems.[3] It is a kappa opioid receptor (KOR) agonist which binds to specific nerve and immune cells to decrease itching and inflammation.[2]

Difelikefalin was approved for medical use in the United States in 2021 and Europe in 2022.[3][2] In the United Kingdom it costs the NHS about £420 per vial as of 2022.[6] In the United States it costs about 2,000 USD per month.[7]

Medical uses

It reduces itching by about 50% as compared to about 30 to 40% with a placebo in people on dialysis.[2]


It is used at a dose of 0.5 mcg/kg.[3]

Mechanism of action

It acts by activating KORs on peripheral nerve terminals and KORs expressed by certain immune system cells.[5] Activation of KORs on peripheral nerve terminals results in the inhibition of ion channels responsible for afferent nerve activity, causing reduced transmission of pain signals, while activation of KORs expressed by immune system cells results in reduced release of proinflammatory, nerve-sensitizing mediators (e.g., prostaglandins).[5]

Society and culture

Legal status

On 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kapruvia, intended for treatment of moderate-to-severe pruritus associated with chronic kidney disease.[8] The applicant for this medicinal product is Vifor Fresenius Medical Care Renal Pharma France.[8] Difelikefalin was approved for medical use in the European Union in April 2022.[2]


It is under development by Cara Therapeutics as an intravenous agent for the treatment of postoperative pain.[5][9][10] An oral formulation has also been developed.[10] Due to its peripheral selectivity, difelikefalin lacks the central side effects like sedation, dysphoria, and hallucinations of previous KOR-acting analgesics such as pentazocine and phenazocine.[5][9] In addition to use as an analgesic, difelikefalin is also being investigated for the treatment of pruritus (itching).[5][9][11] Difelikefalin has completed phase II clinical trials for postoperative pain and has demonstrated significant and "robust" clinical efficacy, along with being safe and well tolerated.[9][10] It has also completed a phase III clinical trial for uremic pruritus in hemodialysis patients.[12]


  1. Janecka A, Perlikowska R, Gach K, Wyrebska A, Fichna J (2010). "Development of opioid peptide analogs for pain relief". Curr. Pharm. Des. 16 (9): 1126–35. doi:10.2174/138161210790963869. PMID 20030621.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Kapruvia EPAR". European Medicines Agency (EMA). 22 February 2022. Archived from the original on 6 May 2022. Retrieved 28 April 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 "Korsuva- difelikefalin injection, solution". DailyMed. Archived from the original on 12 September 2021. Retrieved 12 September 2021.
  4. https://pdf.hres.ca/dpd_pm/00066996.PDF Archived 2022-10-01 at the Wayback Machine[bare URL PDF]
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Raymond S. Sinatra; Jonathan S. Jahr; J. Michael Watkins-Pitchford (14 October 2010). The Essence of Analgesia and Analgesics. Cambridge University Press. pp. 490–491. ISBN 978-1-139-49198-3.
  6. 6.0 6.1 "Difelikefalin". SPS - Specialist Pharmacy Service. 10 December 2015. Archived from the original on 24 October 2021. Retrieved 28 October 2022.
  7. Watnick, Suzanne; Butler, Catherine R. (August 2022). "Difelikefalin: A Novel Therapy for Dialysis Patient Care". Kidney Medicine. 4 (8): 100519. doi:10.1016/j.xkme.2022.100519.
  8. 8.0 8.1 "Kapruvia: Pending EC decision". European Medicines Agency. 24 February 2022. Archived from the original on 27 October 2022. Retrieved 26 February 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. 9.0 9.1 9.2 9.3 Jeffrey Apfelbaum (8 September 2014). Ambulatory Anesthesia, An Issue of Anesthesiology Clinics. Elsevier Health Sciences. pp. 190–. ISBN 978-0-323-29934-3.
  10. 10.0 10.1 10.2 Charlotte Allerton (2013). Pain Therapeutics: Current and Future Treatment Paradigms. Royal Society of Chemistry. pp. 56–. ISBN 978-1-84973-645-9.
  11. Alan Cowan; Gil Yosipovitch (10 April 2015). Pharmacology of Itch. Springer. pp. 307–. ISBN 978-3-662-44605-8.
  12. Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F (2020). "A phase 3 trial of difelikefalin in hemodialysis patients with pruritus". N Engl J Med. 382 (3): 222–232. doi:10.1056/NEJMoa1912770. PMID 31702883.

External links

External sites:
  • Clinical trial number NCT03422653 for "A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)" at ClinicalTrials.gov
  • Clinical trial number NCT03636269 for "CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-2)" at ClinicalTrials.gov