Icatibant
Also known as: Firazyr, HOE 140, HOE-140, JE049, bradykinin B2 receptor antagonist, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin
Synthetic bradykinin B2 receptor antagonist; decapeptide; selective competitive antagonist
What it is
Icatibant (Firazyr) is a self-injected medicine that stops the swelling attacks in hereditary angioedema (HAE), a rare inherited condition where patients can develop sudden, painful, potentially life-threatening swelling of the face, throat, abdomen, or limbs. It is FDA-approved, and patients administer it themselves subcutaneously at the first sign of an attack.
The scientific side
icatibant is a synthetic 10-amino acid peptide structurally analogous to bradykinin, designed to function as a highly selective and competitive antagonist at the bradykinin B2 receptor (B2R). The B2 receptor is a G-protein coupled, seven-transmembrane domain receptor that is constitutively expressed throughout the body, particularly on vascular endothelium, smooth muscle, and sensory neurons. Bradykinin, the endogenous ligand for the B2R, is the principal mediator of the pathological swelling in hereditary angioedema (HAE). In HAE types I and II, mutations in the SERPING1 gene reduce the quantity or functionality of C1-inhibitor (C1-INH), resulting in uncontrolled activation of the contact (kallikrein-kinin) pathway, excessive cleavage of high-molecular-weight kininogen by plasma kallikrein, and a resulting surge in bradykinin production. Bradykinin binding to B2Rs on vascular endothelium activates intracellular signaling cascades that produce prostaglandins, nitric oxide, and arachidonic acid metabolites, collectively causing profound vasodilation and dramatically increased vascular permeability — the hallmark of HAE attacks. Icatibant's structural modifications (including D-amino acid substitutions at positions 3, 7, and 8, and the non-natural amino acid oic at position 8) confer high B2R binding affinity while preventing receptor activation, thereby competitively blocking bradykinin from triggering these vasopermeability responses. At the approved 30 mg subcutaneous dose, icatibant achieves rapid absorption with peak plasma concentrations within approximately 30 minutes. Its pharmacological action halts ongoing bradykinin-mediated vascular leak, allowing acute angioedema attacks to resolve. This same mechanism underlies its investigated utility in ACE inhibitor-induced angioedema, where reduced bradykinin catabolism — rather than overproduction — produces a mechanistically similar bradykinin excess state. The B2R antagonism also has potential utility in other bradykinin-driven conditions including certain viral infections where kinin system dysregulation has been proposed as a pathogenic mechanism.
Class: Synthetic bradykinin B2 receptor antagonist; decapeptide; selective competitive antagonist
Administration & storage
- Administration
- Subcutaneous injection into the abdomen (at least 5 cm from the navel)thighor upper armSlow injection technique recommended to minimize injection site discomfortSelf-injection after appropriate training — supported as equivalent to HCP-administered injection in efficacy and safety
- Storage
- Store below 25°C (77°F). Do not refrigerate or freeze. Keep in original packaging to protect from light. The pre-filled syringe should be inspected visually before use; do not use if particulates are present or if the solution is discolored.
- Cautions
- Icatibant is approved only for adults ≥18 years; safety and efficacy in pediatric patients have not been formally established though real-world off-label use is documented.,Patients with known laryngeal involvement should seek emergency medical care even after self-injecting icatibant, as airway obstruction can be rapid and fatal.,Injection site reactions occur in nearly all treated patients (erythema, swelling, burning, pain at injection site) but are typically mild to moderate, transient, and resolve without treatment.,Icatibant is a bradykinin B2 antagonist — it has no effect on bradykinin B1 receptor activity, histamine, or IgE-mediated reactions; it is NOT appropriate for treatment of allergic (histamine-mediated) angioedema.,Pregnancy: limited data; icatibant should be used in pregnancy only if clearly necessary. Animal reproductive toxicity studies show effects at high doses. Bradykinin plays a role in uterine contractility.,The LactMed database notes that due to its peptide nature (MW 1305 Da) icatibant is likely to be present in breastmilk at very low levels, partially destroyed in the infant GI tract, and minimally absorbed; a waiting period of 6–12 hours post-dose before breastfeeding is recommended as a precaution.
Legal & regulatory status
FDA-approved (NDA 022150) as Firazyr (icatibant acetate) 30 mg/3 mL subcutaneous injection for treatment of acute attacks of hereditary angioedema (HAE) in adults (≥18 years). Approved August 25, 2011. Indicated for…
Icatibant is not included on the current WADA Prohibited List. It is a prescription-only therapeutic peptide with no known performance-enhancing application in sport. It is used exclusively for the treatment of a rare…
Firazyr (icatibant acetate) has received marketing authorization in Canada for treatment of acute HAE attacks in adults with C1 inhibitor deficiency. Canada approval followed the European Medicines Agency (EMA) approval…
What it's studied for
- Acute attacks of hereditary angioedema types I and II — on-demand treatment (FDA-approved indication) Phase III RCT
- Laryngeal hereditary angioedema attacks — life-threatening airway involvement Phase III RCT (open-label and controlled subgroup)
- Self-administration at home for hereditary angioedema — on-demand home therapy Prospective multicenter cohort
- ACE inhibitor-induced angioedema — off-label use in bradykinin-excess angioedema Phase II RCT; conflicting evidence
- Acquired C1 inhibitor deficiency angioedema — off-label acute treatment Clinical review / case series
- Pediatric hereditary angioedema — emerging real-world evidence Retrospective database study / observational
Safety signals
- Injection site reactions (nearly universal)
- Delayed efficacy or non-response in ACE inhibitor-induced angioedema
- Potential for serious cardiac adverse events (rare)
- Pregnancy safety — limited human data; precautionary concern
- Lack of efficacy in histamine-mediated or allergic angioedema
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 30 mg (3 mL) subcutaneous injection | — | Adults with HAE types I/II (approved indication) | Research |
| Unspecified | 30 mg subcutaneous injection | — | Adults with ACE inhibitor-induced angioedema (off-label) | Research |
| subcutaneous injection into the abdomen | 30 mg (one pre-filled 3 mL syringe) | once per attack; repeat at 6-hour intervals if symptoms persist (max 3 injections per 24 hours) | adults with hereditary angioedema types I or II (C1-INH deficiency or dysfunction) |