Introduction
Firazyr (icatibant acetate) is a synthetic bradykinin B2 receptor antagonist approved for the treatment of acute attacks of hereditary angioedema (HAE) in adults. HAE is a rare genetic disorder characterized by recurrent episodes of subcutaneous or submucosal swelling that can be life-threatening when affecting the upper airway. Firazyr represents a targeted therapeutic approach that addresses the underlying pathophysiology of HAE attacks.
Mechanism of Action
Firazyr works as a competitive antagonist at the bradykinin B2 receptor. In hereditary angioedema, deficiency or dysfunction of C1 esterase inhibitor leads to uncontrolled activation of the contact system and subsequent excessive bradykinin production. Bradykinin, acting through B2 receptors, increases vascular permeability, leading to the characteristic swelling episodes. Icatibant binds selectively to B2 receptors, blocking bradykinin-mediated effects and reducing edema formation.
Indications
Firazyr is FDA-approved for the treatment of acute attacks of hereditary angioedema in adults 18 years and older. It is indicated for both subcutaneous and abdominal attacks, as well as laryngeal attacks that can cause airway obstruction.
Dosage and Administration
The recommended dosage is 30 mg administered subcutaneously in the abdominal area. If the attack persists, repeat doses of 30 mg may be administered at intervals of at least 6 hours. No more than 3 doses should be administered within a 24-hour period.
Special Populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment necessary
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of approximately 0.75 hours Distribution: Volume of distribution is approximately 20-30 L Metabolism: Undergoes proteolytic degradation to inactive metabolites Elimination: Terminal half-life is approximately 1-2 hours; primarily eliminated via proteolytic degradation Bioavailability: Approximately 97% following subcutaneous administrationContraindications
Firazyr is contraindicated in patients with known hypersensitivity to icatibant acetate or any component of the formulation.
Warnings and Precautions
- Laryngeal Attacks: Patients experiencing laryngeal attacks should seek immediate medical attention after administration
- Ischemic Heart Disease: Use with caution in patients with acute ischemic heart disease or unstable angina
- Pregnancy: Use only if clearly needed (Pregnancy Category C)
- Breastfeeding: Caution should be exercised when administering to nursing women
Drug Interactions
No formal drug interaction studies have been conducted. However, theoretical interactions may occur with:
- ACE inhibitors (may interfere with Firazyr's mechanism of action)
- Other bradykinin-mediated therapies
- No known interactions with CYP450 enzymes
Adverse Effects
Most common adverse reactions (≥5%):- Injection site reactions (97%): erythema, swelling, pain, pruritus, burning
- Pyrexia (6%)
- Transaminase elevation (5%)
- Dizziness (5%)
- Rash (5%)
- Anaphylactoid reactions (rare)
- Worsening of ischemic heart disease
Monitoring Parameters
- Resolution of angioedema symptoms
- Injection site reactions
- Vital signs during and after administration
- Liver function tests (periodically)
- For laryngeal attacks: continuous airway assessment
Patient Education
- Proper technique for subcutaneous self-administration
- Recognition of HAE attack symptoms
- Importance of seeking emergency care for laryngeal attacks
- Proper storage and handling of medication
- Recognition and reporting of adverse effects
- Carry emergency identification indicating HAE diagnosis
- Have a plan for emergency treatment access
References
1. FDA Prescribing Information: Firazyr (icatibant) injection 2. Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532-541. 3. Longhurst HJ, Bresnick R, Bork K, et al. Icatibant for the treatment of hereditary angioedema: the long-term safety of frequently administered icatibant. Allergy. 2020;75(3):676-684. 4. Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491-1493. 5. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update. Allergy. 2018;73(8):1575-1596.