Ecallantide

{{Short description|Medication}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 414410253

| tradename = Kalbitor | synonyms = DX-88 | Drugs.com = {{drugs.com|monograph|ecallantide}} | DailyMedID = Ecallantide | licence_US = Ecallantide | pregnancy_AU =  | pregnancy_category = | legal_AU =  | legal_CA =  | legal_UK =  | legal_US = Rx-only | routes_of_administration = Subcutaneous injection

| elimination_half-life = 1.5–2.5 hours | excretion = Kidney

| IUPHAR_ligand = 6955 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 460738-38-9 | ATC_prefix = B06 | ATC_suffix = AC03 | PubChem = 118984459 | DrugBank = DB05311 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | UNII_Ref = {{fdacite|changed|FDA}} | UNII = 5Q6TZN2HNM | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1201837 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 34983390  | 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) | C=305 | H=442 | N=88 | O=91 | S=8 }}

'''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.<ref name=Lehmann>{{cite journal | vauthors = Lehmann A | title = Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery | journal = Expert Opinion on Biological Therapy | volume = 8 | issue = 8 | pages = 1187–99 | date = August 2008 | pmid = 18613770 | doi = 10.1517/14712598.8.8.1187 | s2cid = 72623604 }}</ref> 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.<ref name=Lehmann/>

==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.<ref name=Waknine>{{cite web |url=http://www.medscape.com/viewarticle/713401 |title=FDA Approves Ecallantide for Hereditary Angioedema | vauthors = Waknine Y |publisher=Medscape |date=December 4, 2009 |access-date=2009-12-07}}</ref> A single dose requires three separate injections, which are given under the skin.<ref name="2013 Nursebook">{{cite book |title=2013 Nurse's Drug Handbook |date=2013 |publisher=Jones & Bartlett Publishers |location=Burlington, MA |page=391 |edition=12th | isbn = 978-1-284-19536-1 }}</ref>

Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors.<ref>{{cite journal | vauthors = Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, Miner J, Iarrobino R, Chyung Y | display-authors = 6 | title = Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial | journal = Annals of Emergency Medicine | volume = 65 | issue = 2 | pages = 204–13 | date = February 2015 | pmid = 25182544 | doi = 10.1016/j.annemergmed.2014.07.014 }}</ref><ref>{{cite journal | vauthors = Scalese MJ, Reinaker TS | title = Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors | journal = American Journal of Health-System Pharmacy | volume = 73 | issue = 12 | pages = 873–9 | date = June 2016 | pmid = 27261237 | doi = 10.2146/ajhp150482 }}</ref>

==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.<ref name="Dyax">{{cite web |author=Dyax Corp. |year=2009 |title=Full prescibing information Kalbitor |url=http://www.kalbitor.com/pdf/KalbitorFullPrescribingInformation.pdf |access-date=2010-05-02}}</ref>

== Interactions ==

{{as of|2011}}, no interaction studies have been conducted.<ref name="Dyax" />

==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.<ref>{{cite journal | vauthors = Bhoola KD, Figueroa CD, Worthy K | title = Bioregulation of kinins: kallikreins, kininogens, and kininases | journal = Pharmacological Reviews | volume = 44 | issue = 1 | pages = 1–80 | date = March 1992 | doi = 10.1016/S0031-6997(25)00058-4 | pmid = 1313585 }}</ref><ref name="OffermannsRosenthal2008">{{cite book | vauthors = Offermanns S, Rosenthal W |title=Encyclopedia of Molecular Pharmacology|url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA673|access-date=11 December 2010|year=2008|publisher=Springer|isbn=978-3-540-38916-3|pages=673–}}</ref> 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.<ref name="Dyax" /> Ecallantide's inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity.<ref name="NCATS at NIH">{{cite web |title=NCATS Inxight: Drugs — ECALLANTIDE |url=https://drugs.ncats.io/substance/5Q6TZN2HNM |website=drugs.ncats.io |publisher=National Center for Advancing Translational Sciences (NCATS) |access-date=15 May 2019 |language=en}}</ref>

== References == {{reflist}}

Category:Antibody mimetics Category:Hydrolase inhibitors Category:Drugs developed by Takeda Pharmaceutical Company