Ecallantide

Ecallantide
Clinical data
Trade names Kalbitor
Synonyms DX-88
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		 Subcutaneous injection
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Elimination half-life 1.5–2.5 hours
    Excretion Renal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    ChEMBL
    Chemical and physical data
    Formula C305H442N88O91S8
    Molar mass 7053.83 g/mol
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    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]

    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]

    For angioedema due to ACE inhibitors it does not appear to have a benefit.[3][4]

    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.[5]

    Interactions

    As of 2011, no interaction studies have been conducted.[5]

    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.[6][7] 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.[5]

    See also

    • Icatibant, another drug for the treatment of HAE

    References

    1. 1 2 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. ↑ Lewis, LM; Graffeo, C; Crosley, P; Klausner, HA; Clark, CL; Frank, A; Miner, J; Iarrobino, R; Chyung, Y (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.
    4. ↑ Scalese, MJ; Reinaker, TS (15 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.
    5. 1 2 3 Dyax Corp. (2009). "Full prescibing information Kalbitor" (PDF). Retrieved 2010-05-02.
    6. ↑ Bhoola, K. D.; Figueroa, C. D.; Worthy, K. (1992). "Bioregulation of kinins: Kallikreins, kininogens, and kininases". Pharmacological Reviews. 44 (1): 1–80. PMID 1313585.
    7. ↑ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
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