Ecallantide

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.[1] 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.[1]

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
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC305H442N88O91S8
Molar mass7053.90 g·mol−1
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Medical uses

Angioedema

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.[2] A single dose requires three separate injections, which are given under the skin.[3]

Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors.[4][5]

Adverse effects

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.[6]

Interactions

As of 2011, no interaction studies have been conducted.[6]

Mechanism of action

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.[7][8] 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.[6] Ecallantide's inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity.[9]

References
  1. 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.
  2. Waknine Y (December 4, 2009). "FDA Approves Ecallantide for Hereditary Angioedema". Medscape. Retrieved 2009-12-07.
  3. 2013 Nurse's Drug Handbook (12 ed.). Burlington, MA: Jones & Bartlett Publishers. 2013. p. 391.
  4. 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.
  5. 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.
  6. Dyax Corp. (2009). "Full prescibing information Kalbitor" (PDF). Retrieved 2010-05-02.
  7. Bhoola KD, Figueroa CD, Worthy K (March 1992). "Bioregulation of kinins: kallikreins, kininogens, and kininases". Pharmacological Reviews. 44 (1): 1–80. PMID 1313585.
  8. Offermanns S, Rosenthal W (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
  9. "NCATS Inxight: Drugs — ECALLANTIDE". drugs.ncats.io. National Center for Advancing Translational Sciences (NCATS). Retrieved 15 May 2019.
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