Icatibant
A bradykinin receptor blocker that stops hereditary angioedema attacks, and failed at the related condition
Icatibant blocks the bradykinin B2 receptor, the mediator that causes swelling in hereditary angioedema. Approved in 2011 for acute attacks in adults, it is self-injected at the first sign of an attack. In ACE-inhibitor-induced airway swelling, the trials disagree.
What is it?
Hereditary angioedema attacks are driven by bradykinin, not histamine, which is why antihistamines and adrenaline do little. Icatibant blocks the bradykinin B2 receptor directly. Under the skin it is about 97% bioavailable, peaks at roughly 45 minutes and has an elimination half-life of about 1.4 hours, without accumulating over three doses six hours apart (label).
The label is practical: 30 mg injected subcutaneously into the abdomen, repeatable at intervals of at least six hours if the response is inadequate or symptoms return, to a maximum of three injections in 24 hours, and patients may self-administer on recognising an attack. It is approved for adults 18 and over, though a paediatric study exists.
The registration trials were closer than the drug's reputation. In FAST-2, the primary end point (time to symptom relief) was reached in a median 2.0 hours on icatibant against 12.0 hours on tranexamic acid (P < 0.001). In FAST-1, against placebo, the figures were 2.5 against 4.6 hours, which did not reach significance; 13 placebo patients needed rescue medication against 3 on icatibant, which may have masked the difference. No icatibant-related serious adverse events were reported.
Repeated and self-treated attacks behaved like the first. Across the FAST-3 trial and its open-label extension, patients treating one to five attacks reached the onset of symptom relief in a median 1.9 to 2.1 hours, and laryngeal attacks in 1.0 to 2.0 hours. In an open-label study of 97 patients who injected themselves, 89 needed only one injection, median time to relief was 3.8 hours, and 91.7% preferred self-administration to treatment in clinic.
ACE inhibitors cause angioedema through the same mediator, so the drug was an obvious candidate there, and the two randomised trials disagree. In a 2015 trial of 27 patients, complete resolution took a median 8.0 hours on icatibant against 27.1 hours on a glucocorticoid plus antihistamine, and 5 of 13 icatibant patients had fully resolved within four hours against none of 14; one patient on standard therapy needed a tracheotomy. A larger 2017 trial of 121 patients with at least moderately severe upper-airway swelling, treated a median 7.8 hours after onset, found no difference: both groups met discharge criteria in a median 4.0 hours, and symptom relief began at 2.0 hours on icatibant against 1.6 on placebo. Both are carried here rather than the convenient one, and the indication remains hereditary angioedema only.
Children were studied in an open-label trial of 32 patients aged 2 to 17. Among the 22 who were treated during an attack, mostly cutaneous or abdominal and none laryngeal, symptom relief began at a median of 1.0 hour in both children and adolescents. Adverse events, all mild or moderate, occurred in 28.1%, and injection-site redness or swelling in 90.6%, nearly all gone within six hours. A dedicated pharmacokinetic study found exposure rose in proportion to dose from 30 to 90 mg, with half-lives of about 1.5 to 2 hours and no accumulation when 30 mg was repeated every six hours, which is the basis for the label's repeat interval. The US label nonetheless remains limited to adults.
The label's cautions are short. After treating a laryngeal attack, patients should still seek emergency care because of the risk to the airway. Because icatibant blocks bradykinin, it may in theory blunt the blood-pressure-lowering effect of ACE inhibitors; trials excluded people taking them. Injection-site reactions are almost universal and usually brief.
Mechanism of Action
Icatibant blocks the bradykinin B2 receptor, the mediator of swelling in hereditary angioedema attacks.
Bradykinin B2 blockade
Attacks are driven by bradykinin rather than histamine, so blocking its receptor targets the cause directly.
Fast and short
About 97% bioavailable under the skin, peaking at roughly 45 minutes, with a half-life of about 1.4 hours (label).
Shared pathway with ACE inhibitors
ACE inhibitors raise bradykinin, which is why icatibant was tried in their angioedema and why it might blunt their blood-pressure effect.
Published Research
The studies behind icatibant, read from their PubMed abstracts: the FAST trials, repeated and self-treated attacks, children, ACE-inhibitor angioedema, and pharmacokinetics.
The registration trials
In FAST-2 (74 patients), median time to the primary end point (symptom relief) was 2.0 hours on icatibant against 12.0 on tranexamic acid (P < 0.001); in FAST-1 (56 patients) it was 2.5 against 4.6 hours on placebo (P = 0.14), with rescue medication used by 3 icatibant and 13 placebo patients.
FAST-3: repeated attacks, including the larynx
In patients treating one to five attacks, median time to onset of symptom relief was 1.9 to 2.1 hours, and 1.0 to 2.0 hours for laryngeal attacks; two serious adverse events (arrhythmia, chest pain) were judged related.
Self-administration in 97 patients
89 of 97 patients used a single injection, median time to relief was 3.8 hours, no serious adverse events or hospitalisations occurred, and 91.7% preferred self-administration.
Faster than steroids in ACE-inhibitor angioedema
In 27 patients, complete resolution took a median 8.0 hours on icatibant against 27.1 hours on a glucocorticoid plus antihistamine (P = 0.002), and 5 of 13 against 0 of 14 had resolved within four hours.
And no better than placebo in another
In 121 patients with at least moderately severe ACE-inhibitor angioedema of the upper airway, time to discharge criteria was a median 4.0 hours in both groups, symptom relief began at 2.0 against 1.6 hours (P = 0.57), and no secondary endpoint differed.
In children
In 32 patients aged 2 to 17, symptom relief after a single injection began at a median 1.0 hour in the 22 treated during an attack; adverse events, all mild or moderate, occurred in 28.1%. Injection-site reactions affected 90.6% of patients, mostly redness and swelling, and almost all resolved within six hours. Peak concentration came about half an hour after dosing.
Single and repeat dosing
Single 30 mg and 90 mg doses peaked within an hour with dose-proportional exposure and half-lives of 1.48 and 2.00 hours; repeated 30 mg doses six hours apart did not accumulate.
Dosing Data
Firazyr is a single 30 mg injection under the skin of the abdomen, repeatable if the attack persists.
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Side Effects & Contraindications
Reported Side Effects
From the trials above and the Firazyr prescribing information (DailyMed set ed6657ca, version 19, effective July 7, 2025).
Contraindications & Cautions
From the label.
Legal Status
Approved, and designed for self-administration.
Frequently Asked Questions
?How is icatibant given?
30 mg injected under the skin of the abdomen, which patients may do themselves when they recognise an attack; repeat doses at least six hours apart, no more than three in 24 hours.
?Why do antihistamines not work in hereditary angioedema?
Because the swelling is driven by bradykinin rather than histamine, which is the receptor icatibant blocks.
?Does it work for ACE-inhibitor angioedema?
The evidence is split: one randomised trial found faster resolution than steroid plus antihistamine, another found it no better than placebo in moderately severe upper airway swelling.
?What is the most common side effect?
Injection-site reactions, which affected 90.6% of patients in the paediatric study and mostly resolved within six hours.
?Can patients inject it themselves?
Yes; the label allows self-administration, and in an open-label study 89 of 97 self-treating patients needed only one injection, with relief in a median 3.8 hours.
?How long does it last in the body?
The label gives an elimination half-life of about 1.4 hours, with a peak around 45 minutes after injection.
?Does it interact with other drugs?
The label notes it may weaken the blood-pressure-lowering effect of ACE inhibitors, since both act through bradykinin; trials excluded people taking them.
?Is it approved for children?
Not in the US, where the label covers adults 18 and over. An open-label study in 32 patients aged 2 to 17 found symptom relief began at a median of one hour, with mild or moderate side effects.
References
- [fda-pi] Firazyr (icatibant) prescribing information, sections 1 and 2 (DailyMed SPL version 19, effective July 7, 2025; read October 1, 2026).
- [pubmed] Cicardi M, et al. "Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema." N Engl J Med, 2010;363(6):532-41. PMID: 20818888.
- [pubmed] Lumry WR, et al. "Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3." Int Arch Allergy Immunol, 2015;168(1):44-55. PMID: 26556097.
- [pubmed] Aberer W, et al. "Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema." Allergy, 2014;69(3):305-14. PMID: 24438203.
- [pubmed] Baş M, et al. "A randomized trial of icatibant in ACE-inhibitor-induced angioedema." N Engl J Med, 2015;372(5):418-25. PMID: 25629740.
- [pubmed] Sinert R, et al. "Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema." J Allergy Clin Immunol Pract, 2017;5(5):1402-1409.e3. PMID: 28552382.
- [pubmed] Farkas H, et al. "Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema." J Allergy Clin Immunol Pract, 2017;5(6):1671-1678.e2. PMID: 28601641.
- [pubmed] Leach JK, et al. "Pharmacokinetics of single and repeat doses of icatibant." Clin Pharmacol Drug Dev, 2015;4(2):105-11. PMID: 27128215.
Sources & Citations
Studies were read from their PubMed records (October 5, 2026); the label and Drugs@FDA are listed below with their read dates.
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