Icatibant

Overview

Hereditary angioedema is usually caused by C1-esterase inhibitor deficiency or dysfunction, leading to unregulated activation of the contact/kallikrein-kinin system and overproduction of bradykinin. Bradykinin binding to the B2 receptor increases vascular permeability, producing the painful, potentially life-threatening subcutaneous and submucosal swelling that characterizes HAE attacks.

Icatibant blocks this final step by competitively antagonizing the B2 receptor. Its incorporation of non-natural amino acids makes it resistant to peptidase degradation, allowing a clinically useful duration after a single subcutaneous dose. In the pivotal FAST-3 trial, a single 30 mg subcutaneous injection reduced the median time to meaningful symptom relief to about 2 hours versus roughly 20 hours with placebo, and the earlier FAST-1 and FAST-2 studies supported its efficacy. Because it can be self-administered, it enables prompt at-home treatment of attacks.

The most common adverse effect is a transient injection-site reaction (redness, swelling, pain). Additional doses may be given if a response is incomplete, up to a defined daily maximum.

Mechanism of Action

In HAE, deficient or dysfunctional C1-esterase inhibitor permits excess generation of bradykinin, the principal mediator of attacks. Icatibant occupies the B2 receptor competitively, halting bradykinin-induced endothelial retraction and fluid extravasation. Its non-natural amino-acid substitutions render it resistant to peptidase cleavage, giving a sufficient duration of action from a single subcutaneous dose to abort an acute attack.

Reconstitution Calculator