Ecallantide

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	US FDA:link
Pregnancy category	US: C (Risk not ruled out)
Legal status	US: ℞-only
Routes of administration	Subcutaneous injection
Pharmacokinetic data
Biological half-life	1.5–2.5 hours
Excretion	Renal
Identifiers
CAS Number	460738-38-9 Y
ATC code	B06AC03 (WHO)
PubChem	CID: 44152182
IUPHAR/BPS	6955
UNII	5Q6TZN2HNM N
ChEMBL	CHEMBL1201837 N
Chemical data
Formula	C305H442N88O91S8
Molecular mass	7053.83 g/mol (7054 Da)
NY (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. 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.

For angioedema due to ACE inhibitors it does not appear to have a benefit.

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If approved for cardiothoracic surgery, it could become a replacement for aprotinin, which was withdrawn in 2007 after being shown to cause complications.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.

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.

See also

• Icatibant, another drug for the treatment of HAE