Acute hereditary angioedema (HAE) is a rare disease (occurring in about 1/10,000 to 1/50,000 people) characterised by an absent or dysfunctional C1 esterase inhibitor molecule (C1INH). C1INH is an important regulator in the metabolic pathways of complement, kinin-kallikrein, and coagulation factors. The symptoms of the disease are due to local accumulations of bradykinin caused by excessive activation of the complement and kinin pathways as a result of the C1INH deficiency. Bradykinin, a potent inflammatory mediator, causes vasodilatation, stimulates nociceptors and increases vascular permeability, leading to rapid accumulation of fluid in the interstitial tissue with swelling, pain and redness of the affected tissues. These symptoms are mediated by bradykinin B2 receptors. Attacks can be life threatening when laryngeal edema occurs.

Icatibant, an orphan drug, is a selective, competitive bradykinin B2 receptor antagonist. It blocks the action of bradykinin and thus relieves the symptoms of vasodilation, edema and pain.

Icatibant has only been tested as treatment during acute attacks, not as prophylaxis, since it is administered


Almost all subjects in the clinical trials developed self limiting mild reactions (erythema, swelling) at the injection site. There does not appear to be hypersusceptibility in groups of subjects but the study populations are inevitably small. Other common adverse effects include rash, redness of the skin, dizziness, nasal congestion, GI-problems and increased blood creatinine phosphokinase levels.

Since bradykinin has potential cardioprotective properties, icatibant could in theory impair cardiac function and decrease coronary blood flow. Patients with heart disease should be carefully monitored.

Co-treatment with ACE inhibitors is a contraindication for icatibant therapy. Icatibant could decrease the antihypertensive effect of ACE inhibitors, since they exert their vasodilating effect partially via increased bradykinin concentrations.

EPAR of icatibant.