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 |
|
| Pregnancy category |
|
| Routes of administration | Subcutaneous injection |
| Legal status |
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| Pharmacokinetic data | |
| Biological half-life | 1.5–2.5 hours |
| Excretion | Renal |
| Identifiers | |
| CAS Number |
460738-38-9  |
| ATC code | B06AC03 |
| PubChem | CID 44152182 |
| IUPHAR/BPS | 6955 |
| ChemSpider | none |
| UNII |
5Q6TZN2HNM  |
| ChEMBL |
CHEMBL1201837 |
| Chemical data | |
| Formula | C305H442N88O91S8 |
| Molar mass | 7053.83 g/mol |
| (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]
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]
Other
If approved for cardiothoracic surgery, it could become a replacement for aprotinin, which was withdrawn in 2007 after being shown to cause complications.
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.[4]
Interactions
As of 2011, no interaction studies have been conducted.[4]
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.[5][6] 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.[4]
See also
- Icatibant, another drug for the treatment of HAE
References
- 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.
- ↑ Waknine, Yael (December 4, 2009). "FDA Approves Ecallantide for Hereditary Angioedema". Medscape. Retrieved 2009-12-07.
- ↑ 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.
- 1 2 3 Dyax Corp. (2009). "Full prescibing information Kalbitor" (PDF). Retrieved 2010-05-02.
- ↑ Bhoola, K. D.; Figueroa, C. D.; Worthy, K. (1992). "Bioregulation of kinins: Kallikreins, kininogens, and kininases". Pharmacological reviews 44 (1): 1–80. PMID 1313585.
- ↑ 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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