Introduction
Berinert (C1 esterase inhibitor [human]) is a purified, pasteurized, nanofiltered plasma-derived concentrate used for the treatment of hereditary angioedema (HAE) attacks. HAE is a rare genetic disorder characterized by recurrent episodes of swelling in various body parts, including the extremities, face, abdomen, and airways. Berinert provides exogenous C1 esterase inhibitor to restore regulatory control of the complement and contact system pathways.
Mechanism of Action
Berinert contains functional C1 esterase inhibitor (C1-INH), a serine protease inhibitor that regulates multiple proteolytic systems including:
- Complement system (C1r, C1s)
- Contact system (kallikrein, factor XIIa)
- Fibrinolytic system (plasmin)
- Coagulation system (factor XIa)
By inhibiting these pathways, Berinert prevents the generation of bradykinin, the primary mediator of increased vascular permeability and edema formation in HAE attacks.
Indications
FDA-approved for:
- Treatment of acute abdominal, facial, or laryngeal hereditary angioedema attacks in adult and pediatric patients
EMA-approved for:
- Treatment of acute attacks of hereditary angioedema
- Short-term prophylaxis to prevent HAE attacks during medical or dental procedures
Dosage and Administration
Standard dosing: 20 units/kg body weight administered intravenously Administration:- Reconstitute with provided sterile water for injection
- Administer IV over approximately 10 minutes
- May be repeated if necessary
- Pediatric patients: Same weight-based dosing as adults
- Elderly: No dosage adjustment required
- Renal/hepatic impairment: No specific recommendations
Pharmacokinetics
Absorption: Administered intravenously (100% bioavailability) Distribution: Volume of distribution approximately 3-4 L Half-life: Approximately 56 hours Metabolism: Cleared via the reticuloendothelial system Elimination: Primarily through target protease complex formation and subsequent catabolismContraindications
- 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: Rare cases of thrombosis have been reported Hypersensitivity reactions: May occur, including anaphylaxis Transmissible infectious agents: Theoretical risk of transmission of infectious agents despite manufacturing precautions Blood group antibodies: Contains blood group antibodies (anti-A and anti-B); monitor for hemolysisDrug Interactions
No formal drug interaction studies conducted. Theoretical interactions:
- Antifibrinolytic agents: Potential additive effect on thrombosis risk
- Vaccines: Antibodies in preparation may interfere with response to live virus vaccines
Adverse Effects
Common (>1%):- Headache
- Nausea
- Rash
- Injection site reactions
- Thromboembolic events
- Anaphylaxis
- Hemolysis (particularly in non-O blood groups)
Monitoring Parameters
During administration:- Vital signs
- Signs of hypersensitivity reactions
- Resolution of HAE symptoms
- Hemoglobin/hematocrit (in patients with non-O blood groups)
- Signs of thromboembolic events
- Hepatitis and HIV testing (as clinically indicated)
Patient Education
- Recognize early symptoms of HAE attacks
- Seek immediate treatment for laryngeal swelling
- Carry patient identification card provided with medication
- Report any signs of allergic reactions or unusual symptoms
- Inform healthcare providers of blood type
- Understand proper storage and reconstitution procedures for home use
- Report any history of blood clots or cardiovascular disease
References
1. U.S. Food and Drug Administration. Berinert prescribing information. 2021. 2. Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124(4):801-808. 3. Longhurst HJ, Farkas H, Craig T, et al. HAE international home therapy consensus document. Allergy Asthma Clin Immunol. 2010;6(1):22. 4. Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363(6):513-522. 5. European Medicines Agency. Berinert EPAR product information. 2022.