Icatibant

Firazyr, HOE 140, JE 049, Sajazir (US generic brand)

Immune & bioregulators

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Note on this profile. Icatibant is an approved prescription medicine for acute attacks of hereditary angioedema (HAE), supplied as a pre-filled syringe that patients inject themselves. Use for any other purpose is off-label and largely unstudied. This page explains the published science.

1What it is

Icatibant is a small synthetic peptide designed in the late 1980s at Hoechst (Germany) as a stable, long-acting antagonist of bradykinin — a nine-amino-acid peptide the body makes when the contact (kallikrein–kinin) system is activated. Bradykinin itself is in the body's inflammatory toolkit: it dilates vessels, makes them leaky and causes pain. In hereditary angioedema, a genetic shortage of C1-inhibitor lets kallikrein run unchecked, flooding tissues with bradykinin and producing attacks of severe swelling of the skin, gut wall or airway. Icatibant swaps several of bradykinin's residues for unusual amino acids (D-Arg, hydroxyproline, thienylalanine, tetrahydroisoquinoline-carboxylic acid, octahydroindole-carboxylic acid) so it fits the receptor but cannot activate it and survives the enzymes that destroy natural bradykinin within seconds.

It was developed by Jerini, then Shire (now Takeda), approved in the EU in 2008 and the US in 2011, and is one of three on-demand HAE treatments alongside plasma-derived C1-inhibitor and ecallantide. Generic icatibant has been available in the US since 2020 and in the EU since about 2019.

2How it's thought to work

Bradykinin acts on two receptors: B2 (always present, mediates acute swelling) and B1 (induced by inflammation). Icatibant is a selective, competitive B2 antagonist with affinity similar to bradykinin itself.

Blocking B2 stops the endothelial cell contraction and gap formation that let fluid leak into tissue, so an attack already under way stops progressing and resolves as existing fluid is reabsorbed.

It does not touch the underlying cause (low C1-inhibitor or excess kallikrein); it treats the attack, not the disease, which is why prophylactic drugs (C1-inhibitor, lanadelumab, berotralstat, garadacimab) are separate.

Because ACE normally degrades bradykinin, ACE-inhibitor-induced angioedema is also bradykinin-driven, which is why icatibant was tested there (see below).

A selective B2 receptor antagonist occupying the bradykinin pocket without activating it. Bradykinin released during an attack of hereditary angioedema finds nowhere to signal, so the vessel does not leak and the swelling stops progressing.Schematic — not to scale

3What the research shows

Acute HAE attacks

FAST-1 (US, n=56, placebo-controlled) and FAST-2 (Europe, n=74, versus tranexamic acid) reported median time to onset of symptom relief of about 2.5 h versus 4.6 h (placebo) and 2.0 h versus 12.0 h (tranexamic acid); FAST-1 narrowly missed its primary endpoint while FAST-2 met it (Cicardi 2010, NEJM). FAST-3 (n=98, placebo-controlled, cutaneous and abdominal attacks) met its primary endpoint: median time to 50% symptom reduction 2.0 h vs 19.8 h (Lumry 2011, Ann Allergy Asthma Immunol). Open-label extensions covering thousands of attacks showed consistent effect and that self-administration works (Aberer 2014, Allergy). [2][3][4]

Laryngeal attacks

Laryngeal attacks were excluded from the controlled arms for safety, so evidence is from open-label treatment in FAST and registry data (Icatibant Outcome Survey), showing rapid relief in most.

Paediatric HAE

A single-arm study in children and adolescents (n=32) supported EU approval for ages 2 and up (Farkas 2017, J Allergy Clin Immunol). [5]

Graded A (conflicting)

ACE-inhibitor-induced angioedema

A small German (n=27) reported much faster resolution with icatibant than steroid plus antihistamine (8 h vs 27 h) (Baş 2015, NEJM). Two larger trials (CAMEO, n=121; and a Sinert-led US multicentre trial) found no difference from placebo (Sinert 2017, J Allergy Clin Immunol Pract; Straka 2017, J Allergy Clin Immunol). Routine use is not supported; off-label. [6][7]

COVID-19

A small open-label study in hospitalised COVID-19 patients suggested improved oxygenation (van de Veerdonk 2020, JAMA Netw Open); later controlled data did not establish benefit. Off-label and not pursued.

Community / self-directed use

Essentially none outside prescribed HAE patients. Occasional discussion of use for other swelling disorders has no evidence base.

4Reported side effects and interactions

Literature-reported

Injection-site reactions in about 97% — redness, swelling, warmth, burning, itching and pain — typically lasting a few hours and resolving without treatment. Less common: fever, raised liver transaminases, dizziness, nausea, headache, rash. No anaphylaxis signal; no antibody-related loss of effect over repeated use. Safety in pregnancy is limited to registry data (no signal found so far).

Community-reported

none beyond the patient population; no research-community use.

Theoretical. bradykinin has protective effects in the heart during ischaemia, so the label advises caution and clinical monitoring in people with acute ischaemic heart disease or unstable angina, and in the weeks after stroke. Blocking B2 could in principle blunt the blood-pressure effects of ACE inhibitors.

Interactions. none established in formal studies; not metabolised by CYP enzymes. ACE inhibitors and icatibant act on the same pathway in opposite directions; no clinical interaction documented.

Markers researchers commonly monitor

Icatibant treats attacks and needs little laboratory monitoring; the markers below belong to HAE care generally:

Marker	Why it's watched
C4, C1-inhibitor level and function	diagnostic markers of HAE, not changed by icatibant; they confirm the right diagnosis before the drug is prescribed.
Attack diary (frequency, location, time to relief, doses used)	the real outcome measure, and what regulators and registries collect.
Liver transaminases (ALT/AST)	transient rises were seen in trials; checked if symptomatic or on repeated use.
ECG / cardiac symptoms in anyone with ischaemic heart disease	because of the theoretical loss of bradykinin's cardioprotection.
Injection-site inspection	nearly universal reactions; worth recording to distinguish from a spreading attack.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as a 30 mg/3 mL pre-filled syringe with a 25-gauge needle; no . Patients are trained to inject slowly (over about 30 seconds) into the abdominal fat, 5–10 cm from the navel, at the first sign of an attack, and to seek emergency care for any laryngeal attack even after injecting. Store below 25 °C; do not freeze. The site calculator is not applicable.

6Commonly studied alongside

Plasma-derived or recombinant C1-inhibitor (Berinert, Cinryze, Ruconest) and ecallantide as alternative on-demand treatments; lanadelumab, berotralstat, garadacimab and prophylactic C1-inhibitor as long-term prevention that patients use alongside on-demand icatibant; tranexamic acid as a comparator in FAST-2. No research-community pairings.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Firazyr, 2011) for acute HAE attacks in adults 18+; generics from Cipla and Fresenius Kabi (2020), Sandoz and Glenmark (2021), Eugia (2023) and others; Sajazir is a branded generic
European Union	EMA-authorised (Firazyr, 2008) for acute attacks in adults, adolescents and children aged 2 and over; generic icatibant authorised †
United Kingdom	MHRA-licensed (Firazyr and generics); NHS-funded for HAE
Australia	TGA-registered (Firazyr); PBS-listed for HAE †
South Africa	Registered with SAHPRA (Firazyr, Takeda) †
Sport	Not prohibited by WADA

8Open questions

Why it fails in ACE-inhibitor angioedema in larger trials when the mechanism is the same pathway.
Oral B2 antagonists (e.g. deucrictibant, in Phase 3) may replace injection; results due 2025–2026 †.
Long-term safety data in pregnancy and in children under 2 remain limited.

9References

1Hock FJ et al. (1991). Hoe 140, a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. PubMed · DOI
2Cicardi M et al. (2010). Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema (FAST-1 and FAST-2). NEJM. PubMed · DOI
3Lumry WR et al. (2011). Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. PubMed · DOI
4Aberer W et al. (2014). Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema. Allergy. PubMed
5Farkas H et al. (2017). Icatibant for the treatment of hereditary angioedema with C1-inhibitor deficiency in adolescents and in children aged over 2 years. J Allergy Clin Immunol. [verify exact journal] PubMed · DOI
6Baş M et al. (2015). A randomized trial of icatibant in ACE-inhibitor-induced angioedema. NEJM. PubMed · DOI
7Sinert R et al. (2017). Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. PubMed · DOI
8Firazyr (icatibant) US prescribing information and EU Summary of Product Characteristics (current). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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