Introduction
Cinryze (C1 esterase inhibitor [human]) is a plasma-derived therapy approved for the treatment of hereditary angioedema (HAE). HAE is a rare genetic disorder characterized by recurrent episodes of swelling in various body parts, including the extremities, face, abdomen, and airways. Cinryze provides targeted replacement therapy for the deficient C1 esterase inhibitor protein, addressing the underlying pathophysiology of HAE attacks.
Mechanism of Action
Cinryze contains purified human C1 esterase inhibitor, which functions as a serine protease inhibitor. In HAE patients, deficiency or dysfunction of this regulatory protein leads to uncontrolled activation of the contact system and complement pathway, resulting in excessive bradykinin production. Bradykinin is the primary mediator of vascular permeability and edema formation in HAE attacks. Cinryze restores regulatory control by:
- Inhibiting activated C1r and C1s of the classical complement pathway
- Inhibiting plasma kallikrein and factor XIIa of the contact system
- Regulating bradykinin generation and preventing its vasodilatory effects
Indications
FDA-approved indications:
- Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE
- Treatment of acute abdominal or facial attacks of HAE in adult patients
Dosage and Administration
Prophylactic dosing: 1000 units administered intravenously every 3-4 days Acute attack treatment: 1000 units administered intravenously (may be repeated if needed) Administration:- Reconstitute with 10 mL sterile water for injection
- Gently swirl to dissolve (do not shake)
- Administer IV over approximately 10 minutes
- Store under refrigeration (2-8°C)
- Pediatric patients: Safety established ≥6 years
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations
Pharmacokinetics
Absorption: Administered intravenously (100% bioavailability) Distribution: Volume of distribution approximately 2.0-2.5 L Metabolism: Cleared via plasma protease pathways Elimination: Mean half-life approximately 62 hours Steady-state: Achieved within approximately 2 weeks of prophylactic dosingContraindications
- 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: Cases of arterial and venous thrombosis have been reported Hypersensitivity reactions: May occur, including anaphylaxis Transmissible infectious agents: As with all plasma-derived products, potential risk of transmitting infectious agents Monitoring: Observe patients for signs of thrombosis during and after administrationDrug Interactions
- No formal drug interaction studies conducted
- Theoretical potential for interactions with anticoagulants and antiplatelet agents due to thromboembolic risk
- Consider monitoring when administered with other thrombogenic agents
Adverse Effects
Most common adverse reactions (≥2%):- Headache
- Nausea
- Rash
- Diarrhea
- Vomiting
- Abdominal pain
- Fatigue
- Injection site reactions
- Thromboembolic events
- Hypersensitivity reactions
- Anaphylaxis
Monitoring Parameters
Before administration:- Verify HAE diagnosis
- Assess thrombosis risk factors
- Screen for hypersensitivity history
- Monitor for signs of thrombosis
- Observe for hypersensitivity reactions during and after infusion
- Track attack frequency and severity for prophylactic efficacy
- Regular assessment of HAE control
- Monitoring for development of inhibitors (rare)
- Periodic assessment of quality of life measures
Patient Education
Key points for patients:- Understand the signs and symptoms of HAE attacks
- Recognize early symptoms requiring treatment
- Be aware of potential side effects, especially thromboembolic events
- Report any signs of allergic reaction immediately
- Keep a treatment diary to track attack frequency and severity
- Understand proper storage and handling requirements
- Carry medical identification indicating HAE diagnosis
- Inform all healthcare providers about HAE and Cinryze use
- Report travel plans (requires special temperature considerations)
References
1. 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. 2. Cinryze [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2021. 3. 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. 4. Longhurst HJ, Carr S, Khair K. C1-inhibitor concentrate home therapy for hereditary angioedema: a viable, effective treatment option. Clin Exp Immunol. 2007;147(1):11-17. 5. FDA Approval Letter: Cinryze. October 2008. 6. Cicardi M, Bork K, Caballero T, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67(2):147-157.