Ecallantide

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Ecallantide
Systematic (IUPAC) 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)
Clinical data
Trade names Kalbitor
AHFS/Drugs.com monograph
Licence data US FDA:link
Pregnancy cat.
Legal status
Routes Subcutaneous injection
Pharmacokinetic data
Half-life 1.5–2.5 hours
Excretion Renal
Identifiers
CAS number 460738-38-9 YesY
ATC code B06AC03
PubChem CID 44152182
UNII 5Q6TZN2HNM N
ChEMBL CHEMBL1201837 N
Chemical data
Formula C305H442N88O91S8 
Mol. mass 7053.83 g/mol (7054 Da)
 N (what is this?)  (verify)

Ecallantide (trade name Kalbitor, investigational name DX-88) 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] On November 27, 2009, ecallantide was approved by the U.S. Food and Drug Administration for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age.[2]

If approved for cardiothoracic surgery, it could become a replacement for aprotinin,[citation needed] which was withdrawn in 2007 after being shown to cause complications.

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.[3]

Interactions[edit]

As of 2011, no interaction studies have been conducted.[3]

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.[4][5] 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.[3]

See also[edit]

  • Icatibant, another drug for the treatment of HAE

References[edit]

  1. ^ 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 Opin Biol Ther 8 (8): 1187–99. doi:10.1517/14712598.8.8.1187. PMID 18613770. 
  2. ^ Waknine, Yael (December 4, 2009). "FDA Approves Ecallantide for Hereditary Angioedema". Medscape. Retrieved 2009-12-07. 
  3. ^ a b c Dyax Corp. (2009). "Full prescibing information Kalbitor". Retrieved 2010-05-02. 
  4. ^ Bhoola, K. D.; Figueroa, C. D.; Worthy, K. (1992). "Bioregulation of kinins: Kallikreins, kininogens, and kininases". Pharmacological reviews 44 (1): 1–80. PMID 1313585.  edit
  5. ^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.