Ecallantide Explained

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] 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

, no interaction studies have been conducted.

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

Notes and References

  1. Lehmann A . 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 . August 2008 . 18613770 . 10.1517/14712598.8.8.1187 . 72623604 .
  2. Web site: FDA Approves Ecallantide for Hereditary Angioedema . Waknine Y . . December 4, 2009 . 2009-12-07.
  3. Book: 2013 Nurse's Drug Handbook . 2013 . Jones & Bartlett Publishers . Burlington, MA . 391 . 12th . 978-1-284-19536-1 .
  4. Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, Miner J, Iarrobino R, Chyung Y . 6 . 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 . February 2015 . 25182544 . 10.1016/j.annemergmed.2014.07.014 .
  5. Scalese MJ, Reinaker TS . Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors . American Journal of Health-System Pharmacy . 73 . 12 . 873–9 . June 2016 . 27261237 . 10.2146/ajhp150482 .
  6. Web site: Dyax Corp. . 2009 . Full prescibing information Kalbitor . 2010-05-02.
  7. Bhoola KD, Figueroa CD, Worthy K . Bioregulation of kinins: kallikreins, kininogens, and kininases . Pharmacological Reviews . 44 . 1 . 1–80 . March 1992 . 1313585 .
  8. Book: Offermanns S, Rosenthal W . Encyclopedia of Molecular Pharmacology. 11 December 2010. 2008. Springer. 978-3-540-38916-3. 673–.
  9. Web site: NCATS Inxight: Drugs — ECALLANTIDE . drugs.ncats.io . National Center for Advancing Translational Sciences (NCATS) . 15 May 2019 . en.

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