Icatibant
approvedAlso known as: Firazyr, HOE 140
**Mechanism of Action** Icatibant is a synthetic decapeptide that acts as a selective, competitive antagonist of the bradykinin B2 receptor. By blocking bradykinin binding, it inhibits downstream signaling pathways (e.g., nitric oxide and prostaglandin release) that mediate vasodilation, increased vascular permeability, and smooth muscle contraction. This mechanism directly counteracts the pathological bradykinin overproduction underlying hereditary angioedema (HAE) attacks. **Key Research Findings** Clinical trials (e.g., FAST-1, FAST-2, FAST-3) demonstrated that subcutaneous icatibant significantly reduces time to symptom relief in acute HAE attacks, with median onset of symptom improvement within 2 hours versus placebo. Pharmacokinetic studies show rapid absorption (Tmax ~0.75 h) and a half-life of 1–2 hours, supporting single-dose efficacy. Post-marketing data confirm consistent safety, with transient injection-site reactions as the most common adverse event. No evidence of tachyphylaxis or antibody formation has been reported. **Clinical Relevance** Icatibant is approved (FDA, EMA) for self-administered treatment of acute HAE attacks in adults. Its targeted B2 receptor antagonism offers a non-plasma-derived alternative to C1 esterase inhibitors, with comparable efficacy and favorable tolerability. Limitations include lack of efficacy in other bradykinin-mediated conditions (e.g., ACE inhibitor-induced angioedema) and the need for repeated dosing during recurrent attacks. For research purposes only — not medical advice.
Key data
C59H89N19O13SResearch & studies
BK levels were significantly elevated in TAAD patients and mice compared with controls.; In the BAPN-induced model, icatibant significantly attenuated disease progression, reducing TAAD incidence and mortality independently of blood pressure.; Excessive BK activated endothelial B2R, elevating intracellular superoxide, suppressing NO production, and causing endothelial damage and TAAD.; Icatibant reversed these changes by restoring P-VASP levels and NO bioavailability.
Three open-label phase III studies covering 43 pediatric patients (ages 0-17) were identified.; Median symptom relief onset was 1 hour, with minimum symptoms reached within 2 hours, though repeated dosing showed variability.; Icatibant was well tolerated; injection-site reactions were most common and no serious treatment-related events occurred.; Self- or caregiver administration was feasible and effective in adolescents.
Symptomatic patients were predominantly female (86.3% vs 30.8% male, p<0.0001), with a mean age at first attack of 24±12 years.; 49% of HAE-FXII patients were estrogen-dependent versus 0% of HAE-PLG patients (p<0.01).; 91% of HAE-PLG patients received at least one icatibant treatment with 100% efficacy; 67% of HAE-FXII patients were treated at least once (56% icatibant, 54% C1Inh concentrate during pregnancy).; Long-term prophylaxis was used in 12.6% of HAE-FXII and 47.4% of HAE-PLG patients; tranexamic acid rendered 66.7% of HAE-PLG attack-free, and lanadelumab rendered 100% of HAE-FXII asymptomatic.
Skin mast cells degranulated in response to both substance P and icatibant, relying on Gi proteins and calcium channels.; Gq and PI3K contributed more strongly to exocytosis with icatibant, while JNK was more relevant for substance P.; Both agonists activated ERK, PI3K/AKT, and weakly p38.; In contrast to LAD2 cells, icatibant was at least as potent as substance P in eliciting MRGPRX2 internalization and (cross-)desensitization in skin mast cells.
Plasma-derived C1-inhibitor is the treatment of choice for HAE during pregnancy due to limited knowledge and experience with other options.; The authors' pregnant nC1-INH HAE patient treated with icatibant experienced no adverse effects or abnormalities.; Attack frequency in the patient continued at more or less the same rate during pregnancy.; Icatibant is considered a safe choice for on-demand HAE treatment during pregnancy in cases with limited attack frequency.
Icatibant effectiveness in real-world settings is comparable to clinical trials.; One dose is effective for the majority of attacks.; Early treatment, facilitated by self-administration, leads to faster resolution and shorter attack duration.; Effectiveness and safety are demonstrated across diverse patient subgroups, including children/adolescents and elderly patients.
Frequently asked questions
What is Icatibant?
**Mechanism of Action** Icatibant is a synthetic decapeptide that acts as a selective, competitive antagonist of the bradykinin B2 receptor. By blocking bradykinin binding, it inhibits downstream signaling pathways (e.g., nitric oxide and prostaglandin release) that mediate vasodilation, increased vascular permeability
How does Icatibant work?
Selective bradykinin B2 receptor antagonist decapeptide approved for acute attacks of hereditary angioedema.
What is the research status of Icatibant?
Icatibant is currently classified as approved, with 780 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Icatibant?
Icatibant has a molecular weight of approximately 1304.5 g/mol (formula C59H89N19O13S).
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