Skip to content
approvedCardiovascular

Icatibant

Also known as: Firazyr, HOE 140, Icatibant Acetate, Bradykinin B2 Receptor Antagonist

Icatibant (Firazyr) is a synthetic decapeptide and selective bradykinin B2 receptor antagonist approved by the FDA and EMA for the treatment of acute hereditary angioedema (HAE) attacks in adults. Derived from the bradykinin sequence with five non-natural amino acid substitutions for metabolic stability, icatibant competitively blocks bradykinin from binding its B2 receptor, rapidly resolving the vascular permeability, edema, and pain that characterize HAE attacks. It was the first subcutaneously self-administered targeted therapy for acute HAE.

4 cited references·6 researched benefits

Quick Answer

Icatibant (Firazyr) is an FDA-approved synthetic decapeptide that blocks the bradykinin B2 receptor for treating acute hereditary angioedema (HAE) attacks. Administered as a single 30 mg subcutaneous injection, it rapidly reduces swelling by preventing bradykinin from causing vascular leakage. It has a half-life of 1-2 hours and provides symptom relief within 30-60 minutes. It was the first self-injectable targeted therapy for acute HAE episodes.

Key Facts

Mechanism
Icatibant is a competitive, selective antagonist of the bradykinin B2 receptor. In hereditary angioedema (caused by C1-inhibitor deficiency), uncontrolled activation of the kallikrein-kinin system generates excess bradykinin. Bradykinin binding to B2 receptors on vascular endothelial cells activates phospholipase C, increasing intracellular calcium and triggering nitric oxide and prostacyclin release. This causes vasodilation, increased vascular permeability, and tissue edema — the hallmarks of angioedema attacks. Icatibant contains five non-natural amino acids (D-Arg, Hyp, Thi, D-Tic, Oic) that confer resistance to enzymatic degradation while maintaining high B2 receptor binding affinity (Ki ~1 nM). By blocking bradykinin access to B2 receptors, icatibant rapidly reverses the vascular permeability increase.
Research Status
approved
Half-Life
~1-2 hours
Molecular Formula
C₅₉H₈₉N₁₉O₁₃S
Primary Use
Cardiovascular
Table of Contents

Benefits

  • Rapid symptom relief — median time to onset of improvement ~30-60 minutes after subcutaneous injectionstrong
  • Targeted mechanism — specifically blocks the bradykinin B2 receptor responsible for angioedema pathophysiologystrong
  • Self-administration — patients can self-inject subcutaneously without requiring hospital visitsstrong
  • Effective across all HAE attack locations including potentially life-threatening laryngeal attacksstrong
  • Well-tolerated with mainly local injection site reactions as the primary side effectstrong
  • Investigational use in ACE inhibitor-induced angioedema (off-label)moderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (FDA-approved)30 mg (3 mL of 10 mg/mL solution)Single injection per attack; may repeat every 6 hours if needed (maximum 3 injections per 24 hours)Injected slowly into the abdominal skin. Self-administration after training by healthcare provider. Pre-filled syringe with 25-gauge needle. Can be carried at room temperature (up to 25°C/77°F). No dose adjustment for renal or hepatic impairment.
Subcutaneous injection (investigational — ACE inhibitor angioedema)30 mgSingle dose; may repeat onceOff-label use for ACE inhibitor-induced angioedema, which shares the bradykinin-mediated mechanism. Multiple case series and small trials suggest benefit. Not FDA-approved for this indication.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Injection site reactions — erythema, swelling, burning, and itching at injection site (occurs in ~97% but generally mild and transient)common
  • Headachecommon
  • Nauseacommon
  • Feverrare
  • Transient increase in liver enzymesrare
  • Dizzinesscommon
  • Rashrare

Frequently Asked Questions

What is hereditary angioedema and how does icatibant treat it?
Hereditary angioedema (HAE) is a rare genetic disorder (affecting ~1 in 50,000 people) caused by deficiency or dysfunction of C1-inhibitor, a serine protease inhibitor that normally controls the kallikrein-kinin and complement systems. Without functioning C1-inhibitor, kallikrein becomes overactive and generates excessive bradykinin, which triggers sudden episodes of severe swelling (angioedema) in the skin, gastrointestinal tract, and potentially life-threatening laryngeal swelling. Icatibant blocks the bradykinin B2 receptor, directly counteracting the cause of swelling at the receptor level.
How quickly does icatibant work for an HAE attack?
In the FAST-3 clinical trial, icatibant provided onset of symptom relief in a median of approximately 2 hours for cutaneous attacks and 0.8 hours for abdominal attacks, with most patients experiencing noticeable improvement within 30-60 minutes of injection. Complete resolution of symptoms occurred in a median of approximately 8-16 hours depending on attack location. About 10% of patients require a second injection at 6 hours for refractory symptoms. Early treatment at the first sign of an attack generally leads to faster resolution.
Can icatibant be used for ACE inhibitor-induced angioedema?
ACE inhibitor-induced angioedema is also bradykinin-mediated (ACE degrades bradykinin, so ACE inhibitors cause bradykinin accumulation), making icatibant a logical treatment. Multiple case series and the small randomized CAMEO trial have shown that icatibant reduces time to symptom resolution compared to standard care. However, this remains an off-label use. Emergency department protocols increasingly include icatibant for severe ACE inhibitor angioedema, particularly laryngeal involvement, though larger trials are needed for formal approval.
How does icatibant compare to other HAE treatments?
For acute HAE attacks, treatment options include: icatibant (bradykinin B2 antagonist — subcutaneous, self-injectable); C1-inhibitor replacement (Berinert, Cinryze — IV; Haegarda — subcutaneous); ecallantide (kallikrein inhibitor — subcutaneous, requires healthcare administration due to anaphylaxis risk); and fresh frozen plasma (emergency use). For prophylaxis, options include lanadelumab (anti-kallikrein antibody), berotralstat (oral kallikrein inhibitor), and C1-inhibitor replacement. Icatibant is often preferred for acute treatment because of its ease of self-administration, rapid onset, and favorable safety profile.
Why does icatibant contain non-natural amino acids?
Natural bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) has a half-life of only about 15-30 seconds due to rapid degradation by kininases (ACE, aminopeptidase P, carboxypeptidase N). Icatibant replaces five amino acids with non-natural analogs: D-Arg (position 1), Hyp (hydroxyproline, position 3), Thi (β-2-thienyl-L-alanine, positions 5 and 8), and D-Tic (D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, position 7). These substitutions prevent enzymatic cleavage while converting the peptide from an agonist (bradykinin) to an antagonist that blocks the receptor without activating it.

References

  1. 1
    Icatibant for the treatment of acute attacks of hereditary angioedema (FAST-3 trial)(2011)PubMed ↗
  2. 2
    Icatibant: a review of its use in hereditary angioedema and angiotensin-converting enzyme inhibitor-induced angioedema(2012)PubMed ↗
  3. 3
    Bradykinin B2 receptor antagonism: a novel approach to hereditary angioedema therapy(2007)PubMed ↗
  4. 4
    Icatibant for ACE inhibitor-induced angioedema: the CAMEO randomized trial(2015)PubMed ↗

Latest Research

Last updated: 2026-02-19