Introduction
Haegarda® (C1 esterase inhibitor subcutaneous [human]) is a plasma-derived therapy approved for routine prophylaxis to prevent hereditary angioedema (HAE) attacks. Manufactured by CSL Behring, it represents a significant advancement in HAE management by offering convenient subcutaneous administration for long-term preventive treatment.
Mechanism of Action
Haegarda contains C1 esterase inhibitor, which functions by replenishing deficient or dysfunctional C1 esterase inhibitor protein in patients with HAE. This enzyme regulates the complement system and contact activation pathways. By restoring physiological levels of functional C1 inhibitor, Haegarda prevents excessive kallikrein activation and subsequent bradykinin production, which is the primary mediator of HAE attacks involving increased vascular permeability and edema formation.
Indications
Haegarda is FDA-approved for routine prophylaxis to prevent hereditary angioedema attacks in adolescent and adult patients. It is indicated for:
- Prevention of HAE type I and II attacks
- Reducing frequency and severity of angioedema episodes
- Long-term prophylactic management
Dosage and Administration
Standard dosing: 60 IU/kg administered subcutaneously twice weekly Administration:- Administer via subcutaneous injection in the abdominal area
- Rotate injection sites to prevent local reactions
- Allow refrigerated product to reach room temperature (15-25°C) before administration
- Do not shake the reconstituted solution
- Use within 3 hours after reconstitution
- No dosage adjustment required for renal or hepatic impairment
- Elderly patients: Use standard dosing
- Pediatric patients: Safety and effectiveness established for adolescents (≥12 years)
Pharmacokinetics
Absorption: Bioavailability approximately 40% following subcutaneous administration Distribution: Volume of distribution approximately 4-5 L Metabolism: Undergoes catabolism through plasma protease pathways Elimination: Mean terminal half-life approximately 62 hours Steady-state: Achieved within 2-3 weeks of initiationContraindications
- History of anaphylaxis or severe systemic reaction to C1 esterase inhibitor preparations
- Known hypersensitivity to any components of the product
Warnings and Precautions
Thromboembolic events: Monitor for signs of thrombosis, particularly in patients with known risk factors Hypersensitivity reactions: May occur; monitor patients during and after administration Transmissible infectious agents: As with all plasma-derived products, theoretical risk of transmitting infectious agents exists Monitoring: Observe patients for signs of fluid overload in those at riskDrug Interactions
No formal drug interaction studies conducted. However:
- Theoretical potential for interactions with other anticoagulant or fibrinolytic therapies
- Caution advised when administering with medications affecting coagulation
- No known interactions with androgens or ACE inhibitors
Adverse Effects
Most common adverse reactions (≥5%):- Injection site reactions (bruising, redness, pain, swelling)
- Headache
- Rash
- Diarrhea
- Thromboembolic events (rare)
- Hypersensitivity reactions
- Anaphylaxis (rare)
Monitoring Parameters
Baseline:- HAE attack frequency and severity assessment
- Coagulation parameters in at-risk patients
- Allergy history
- Frequency and severity of breakthrough attacks
- Injection site reactions
- Signs of hypersensitivity
- Thrombotic events in high-risk patients
- Patient adherence and technique assessment
- Annual comprehensive metabolic panel
- Quality of life assessment
- Treatment efficacy evaluation
Patient Education
Key points for patients:- Proper injection technique and site rotation
- Recognition of breakthrough attacks requiring rescue medication
- Storage and handling instructions (refrigerate at 2-8°C)
- Recognition of hypersensitivity reactions
- Importance of adherence to prescribed schedule
- When to seek emergency medical care
- Carry HAE identification card
- Report any new medications to healthcare provider
- Demonstrate proper subcutaneous injection technique
- Teach appropriate needle disposal
- Provide guidance on managing missed doses
References
1. Longhurst H, et al. Efficacy and safety of subcutaneous C1-inhibitor for prevention of attacks of hereditary angioedema: the COMPACT trial. J Allergy Clin Immunol. 2017;140(4):1050-1057. 2. Haegarda® [package insert]. Kankakee, IL: CSL Behring LLC; 2020. 3. Busse PJ, et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021;9(1):132-150. 4. Craig TJ, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012;5(12):182-199. 5. FDA Approval: Haegarda (C1 esterase inhibitor subcutaneous [human]). US Food and Drug Administration. 2017.
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.