Ecallantide (trade name Kalbitor) is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

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 Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

which was developed from a Kunitz domain through

phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...

to mimic antibodies inhibiting kallikrein.

Medical uses

Angioedema

On November 27, 2009, ecallantide was approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

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 Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

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

, 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.

References