fbpx
Wikipedia

Ecallantide

April 10, 2024

Ecallantide (trade name Kalbitor) is a drug used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery.[2] It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein.[2]

Ecallantide
Clinical data
Trade namesKalbitor
Other namesDX-88
AHFS/Drugs.comMonograph
License data
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life1.5–2.5 hours
ExcretionKidney
Identifiers
  • [Glu20,Ala21,Arg36,Ala38,His39,Pro40,Trp42]tissue factor pathway inhibitor (human)-(20-79)-peptide (modified on reactive bond region Kunitz inhibitor 1 domain containing fragment)
CAS Number
  • 460738-38-9 Y
PubChem CID
  • 118984459
IUPHAR/BPS
  • 6955
DrugBank
  • DB05311 Y
ChemSpider
  • 34983390 Y
UNII
  • 5Q6TZN2HNM
ChEMBL
  • ChEMBL1201837 N
CompTox Dashboard (EPA)
  • DTXSID90196709
Chemical and physical data
FormulaC305H442N88O91S8
Molar mass7053.90 g·mol−1
 NY (what is this?)  (verify)

Medical uses edit

Angioedema edit

On November 27, 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age.[3] A single dose requires three separate injections, which are given under the skin.[4]

Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors.[5][6]

Adverse effects edit

The most common adverse effects are headache, nausea, fatigue and diarrhea. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infections, fever, vomiting, itching and upper abdominal pain. Up to 4% of patients showed anaphylaxis, which led to a black box warning in the US.[7]

Interactions edit

As of 2011, no interaction studies have been conducted.[7]

Mechanism of action edit

HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease that is responsible for liberating bradykinin from its precursor kininogen.[8][9] An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE.

Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein.[7] Ecallantide's inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity.[10]

References edit

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ a b Lehmann A (August 2008). "Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery". Expert Opinion on Biological Therapy. 8 (8): 1187–99. doi:10.1517/14712598.8.8.1187. PMID 18613770. S2CID 72623604.
  3. ^ Waknine Y (December 4, 2009). "FDA Approves Ecallantide for Hereditary Angioedema". Medscape. Retrieved 2009-12-07.
  4. ^ 2013 Nurse's Drug Handbook (12th ed.). Burlington, MA: Jones & Bartlett Publishers. 2013. p. 391. ISBN 978-1-284-19536-1.
  5. ^ Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, et al. (February 2015). "Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial". Annals of Emergency Medicine. 65 (2): 204–13. doi:10.1016/j.annemergmed.2014.07.014. PMID 25182544.
  6. ^ Scalese MJ, Reinaker TS (June 2016). "Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors". American Journal of Health-System Pharmacy. 73 (12): 873–9. doi:10.2146/ajhp150482. PMID 27261237.
  7. ^ a b c Dyax Corp. (2009). "Full prescibing information Kalbitor" (PDF). Retrieved 2010-05-02.
  8. ^ Bhoola KD, Figueroa CD, Worthy K (March 1992). "Bioregulation of kinins: kallikreins, kininogens, and kininases". Pharmacological Reviews. 44 (1): 1–80. PMID 1313585.
  9. ^ Offermanns S, Rosenthal W (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
  10. ^ "NCATS Inxight: Drugs — ECALLANTIDE". drugs.ncats.io. National Center for Advancing Translational Sciences (NCATS). Retrieved 15 May 2019.

April 10, 2024
ecallantide, trade, name, kalbitor, drug, used, treatment, hereditary, angioedema, prevention, blood, loss, cardiothoracic, surgery, inhibitor, protein, kallikrein, amino, acid, polypeptide, which, developed, from, kunitz, domain, through, phage, display, mimi. Ecallantide trade name Kalbitor is a drug used for the treatment of hereditary angioedema HAE and in the prevention of blood loss in cardiothoracic surgery 2 It is an inhibitor of the protein kallikrein and a 60 amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein 2 EcallantideClinical dataTrade namesKalbitorOther namesDX 88AHFS Drugs comMonographLicense dataUS DailyMed Ecallantide US FDA EcallantideRoutes ofadministrationSubcutaneous injectionATC codeB06AC03 WHO Legal statusLegal statusUS WARNING 1 Rx onlyPharmacokinetic dataElimination half life1 5 2 5 hoursExcretionKidneyIdentifiersIUPAC name Glu20 Ala21 Arg36 Ala38 His39 Pro40 Trp42 tissue factor pathway inhibitor human 20 79 peptide modified on reactive bond region Kunitz inhibitor 1 domain containing fragment CAS Number460738 38 9 YPubChem CID118984459IUPHAR BPS6955DrugBankDB05311 YChemSpider34983390 YUNII5Q6TZN2HNMChEMBLChEMBL1201837 NCompTox Dashboard EPA DTXSID90196709Chemical and physical dataFormulaC 305H 442N 88O 91S 8Molar mass7053 90 g mol 1 N Y what is this verify Contents 1 Medical uses 1 1 Angioedema 2 Adverse effects 3 Interactions 4 Mechanism of action 5 ReferencesMedical uses editAngioedema edit On November 27 2009 ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age 3 A single dose requires three separate injections which are given under the skin 4 Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors 5 6 Adverse effects editThe most common adverse effects are headache nausea fatigue and diarrhea Less common but observed in more than 5 of patients in clinical trials are respiratory tract infections fever vomiting itching and upper abdominal pain Up to 4 of patients showed anaphylaxis which led to a black box warning in the US 7 Interactions editAs of 2011 update no interaction studies have been conducted 7 Mechanism of action editHAE is caused by a mutation of the C1 inhibitor gene Defective or missing C1 inhibitor permits activation of kallikrein a protease that is responsible for liberating bradykinin from its precursor kininogen 8 9 An excess of bradykinin leads to fluid leakage from blood vessels causing swelling of tissues typical of HAE Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein 7 Ecallantide s inhibitory constant Ki for kallikrein is 25 picoMolar indicating high affinity 10 References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved 22 Oct 2023 a b Lehmann A August 2008 Ecallantide DX 88 a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on pump cardiothoracic surgery Expert Opinion on Biological Therapy 8 8 1187 99 doi 10 1517 14712598 8 8 1187 PMID 18613770 S2CID 72623604 Waknine Y December 4 2009 FDA Approves Ecallantide for Hereditary Angioedema Medscape Retrieved 2009 12 07 2013 Nurse s Drug Handbook 12th ed Burlington MA Jones amp Bartlett Publishers 2013 p 391 ISBN 978 1 284 19536 1 Lewis LM Graffeo C Crosley P Klausner HA Clark CL Frank A et al February 2015 Ecallantide for the acute treatment of angiotensin converting enzyme inhibitor induced angioedema a multicenter randomized controlled trial Annals of Emergency Medicine 65 2 204 13 doi 10 1016 j annemergmed 2014 07 014 PMID 25182544 Scalese MJ Reinaker TS June 2016 Pharmacologic management of angioedema induced by angiotensin converting enzyme inhibitors American Journal of Health System Pharmacy 73 12 873 9 doi 10 2146 ajhp150482 PMID 27261237 a b c Dyax Corp 2009 Full prescibing information Kalbitor PDF Retrieved 2010 05 02 Bhoola KD Figueroa CD Worthy K March 1992 Bioregulation of kinins kallikreins kininogens and kininases Pharmacological Reviews 44 1 1 80 PMID 1313585 Offermanns S Rosenthal W 2008 Encyclopedia of Molecular Pharmacology Springer pp 673 ISBN 978 3 540 38916 3 Retrieved 11 December 2010 NCATS Inxight Drugs ECALLANTIDE drugs ncats io National Center for Advancing Translational Sciences NCATS Retrieved 15 May 2019 Retrieved from https en wikipedia org w index php title Ecallantide amp oldid 1190952097, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.