Ecallantide

Ecallantide

Clinical data
Trade names	Kalbitor
Other names	DX-88
AHFS/Drugs.com	Monograph
License data	US DailyMed: Ecallantide US FDA: Ecallantide
Routes of administration	Subcutaneous injection
ATC code	B06AC03 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Elimination half-life	1.5–2.5 hours
Excretion	Kidney
Identifiers
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)
CAS Number	460738-38-9 checkY
PubChem CID	118984459
IUPHAR/BPS	6955
DrugBank	DB05311 checkY
ChemSpider	34983390 checkY
UNII	5Q6TZN2HNM
ChEMBL	ChEMBL1201837 ☒N
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C305H442N88O91S8
Molar mass	7053.90 g·mol−1
☒NcheckY (what is this?)  (verify)

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. 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.

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. A single dose requires three separate injections, which are given under the skin.

Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors.

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.

Interactions

As of 2011, 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. 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.