Trade names Kalbitor License data US FDA: ECALLANTIDE ATC code B06AC03 (WHO) | AHFS/Drugs.com Monograph Routes of
administration Subcutaneous injection | |
Pregnancy
category US: C (Risk not ruled out) | ||
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.
Contents
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If approved for cardiothoracic surgery, it could become a replacement for aprotinin, which was withdrawn in 2007 after being shown to cause complications.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.