Generic Name: C1-Esterase Inhibitor (Human)
Class: Complement Inhibitors
Complement 1 (C1)-esterase inhibitor is a naturally occurring inhibitor of certain serine proteases (e.g., C1 complement, kallikrein, coagulation factor XIIa, plasmin) involved in the complement, coagulation (contact), and fibrinolytic systems.1 2 4 5 6 7 8 10 11 12 19
Uses for Cinryze
Hereditary Angioedema: Prevention of Angioedema Attacks
Long-term prophylaxis recommended in patients with HAE who have frequent or severe attacks of angioedema.2 5 6 11 12 13 15 16 19 Consider C1-esterase inhibitor (human) when standard prophylactic regimens (e.g., attenuated androgens, antifibrinolytic agents) are ineffective, not tolerated, or contraindicated.5 8 9 11 12 13
Hereditary Angioedema: Treatment of Acute Angioedema Attacks
Although C1-esterase inhibitor concentrates generally are considered treatment of choice for acute attacks of HAE†, C1-esterase inhibitor (Cinryze ) currently is approved in the US only for prevention of such events.6 8 14 18 19
Cinryze Dosage and Administration
Administer by IV infusion.1
May be self-administered; however, patients should not attempt to self-administer unless appropriate training is provided by a clinician.1
Do not mix with any other drug or solution.1
Vials are for single use only; discard any unused portions.1
Allow vials of drug and diluent (sterile water for injection) to reach room temperature prior to reconstitution; protect unreconstituted drug from light.1
Reconstitute vial containing 500 units of C1-esterase inhibitor (human) with 5 mL of sterile water for injection using a double-ended transfer needle; vacuum will draw in the diluent.1 Do not use vials that lack a vacuum.1 Gently swirl until powder is completely dissolved.1 Resultant solution contains 100 units/mL.1 Discard the reconstituted solution if turbid or discolored.1 Prepare a total of 2 vials to obtain a single 1000-unit dose.1 Use filter needle to withdraw reconstituted contents of both vials into a syringe; remove filter needle and replace with another suitable needle or infusion set prior to administration.1 Observe proper aseptic technique since the drug contains no preservatives.1 Administer within 3 hours of reconstitution.1
Rate of Administration
Infuse IV over 10 minutes at a rate of approximately 1 mL/minute.1
Routine Prophylaxis of Angioedema AttacksIV
Adolescents 13–18 years of age: 1000 units every 3–4 days.1 20 Some clinicians recommend that the frequency of administration be individualized using the lowest possible frequency to prevent acute attacks.5
Routine Prophylaxis of Angioedema AttacksIV
1000 units every 3–4 days.1 Other dosing frequencies (e.g., every 5–7 days) have been used.5 9 13 15 Some clinicians recommend that frequency of administration be individualized using the lowest possible frequency to prevent acute attacks.5
Cautions for Cinryze
Known life-threatening hypersensitivity (e.g., anaphylaxis) to C1-esterase inhibitor (human) or any ingredient in the formulation.1
Risk of thrombosis with high doses.1 17 Serious thromboembolic events, including death, reported in neonates, infants, and children receiving excessive doses up to 500 units/kg of C1-esterase inhibitor (human).1 17
Risk of Transmissible Agents in Plasma-derived Preparations
Potential vehicle for transmission of human viruses (e.g., HIV, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV], parvovirus B19) or other infectious agents (e.g., Creutzfeldt-Jakob disease [CJD]).1 9 12 13 Risk substantially reduced with current donor screening practices and viral inactivating procedures; however, possibility of disease transmission still exists.1 12 15 19 No cases of parvovirus B19, HBV, HCV, or HIV reported to date with currently available C1-esterase inhibitor (human).1 5 8 15
Weigh risks of viral infection against benefits of therapy.1 12 Some experts recommend that patients who receive long-term treatment with blood products be vaccinated against hepatitis A and hepatitis B.12 13 Report any suspected infections thought to be associated with C1-esterase inhibitor (human) to the manufacturer at 877-945-1000.1
Risk of severe hypersensitivity reactions (e.g., hives, urticaria, chest tightness, wheezing, hypotension, anaphylaxis).1 If hypersensitivity occurs, discontinue drug immediately and initiate appropriate treatment.1 Because symptoms of hypersensitivity can resemble acute attacks of hereditary angioedema, carefully consider treatment method.1 Epinephrine should be available for immediate use.1
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.1
Common Adverse Effects
Interactions for Cinryze
No formal drug interaction studies to date.1
Plasma concentrations of C1-esterase inhibitor increase immediately (i.e., within 1 hour) following IV administration; C4 levels subsequently rise 2–24 hours later, indicating consumption of C1-esterase inhibitor and stabilization of the complement activation system.1 5 6 8 15
Not known whether C1-esterase inhibitor is distributed into milk.1
Powder for Injection
Store reconstituted solution at 20–25°C for up to 3 hours.1
Naturally occurring serine protease inhibitor that principally regulates the activation of the complement and intrinsic coagulation (e.g., contact system) pathways.1 2 4 5 6 7 8 10 11 12 19 Also plays a role in the fibrinolytic system.1 2 6 8 12
Regulates contact system activation by inhibiting plasma kallikrein and coagulation factor XIIa; such actions prevent formation of bradykinin, the presumed mediator of increased vascular permeability in HAE.1 2 4 5 6 7 10 11 12 13
Preparation of highly purified C1-esterase inhibitor derived from pooled human plasma.1 8 19 Undergoes a series of viral reduction steps (e.g., pasteurization, precipitation, nanofiltration) to reduce risk of viral transmission.1 8 19
Advice to Patients
Importance of discussing potential risks and benefits of therapy with patient prior to prescribing or administering the drug.1
Importance of using C1-esterase inhibitor (human) only for the condition prescribed.1
Advise patients to notify a clinician inmediately, if swelling is not controlled following treatment with C1-esterase inhibitor (human).1
Risk of transmission of human viruses (i.e., HAV, HBV, HCV, HIV, parvovirus B19) and other infectious agents (i.e., causative agent for Creutzfeldt-Jakob disease).1 12 Advise patient that current donor screening and viral inactivating procedures have reduced, but not completely eliminated the risk of disease transmission.1
Advise patients not to use C1-esterase inhibitor (human) if they have experienced life-threatening immediate hypersensitivity reactions (e,g., anaphylaxis).1 Importance of discontinuing therapy and immediately informing clinician if any symptoms of hypersensitivity (e.g., rash, hives, swelling of the face, chest tightness, fast heartbeat, wheezing, breathing difficulty, turning blue [lips, gum], low BP, faintness, anaphylaxis) occur.1
Advise patients to bring an adequate supply of C1-esterase inhibitor (human) while traveling and to consult a clinician prior to travel.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
For injection, for IV infusion
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions September 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Lev Pharmaceuticals. Cinryze (C1 inhibitor, human) prescribing information. New York, NY; 2009 May.
2. Zuraw BL. Hereditary angioedema. N Engl J Med. 2008; 359:1027-36. [PubMed 18768946]
3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; [May 5, 2003]. From FDA web site.
4. Maplethorpe C. C1 inhibitor (human) clinical review. Rockville, MD: Food and Drug Administration; 2008 Oct 20.
5. Prematta MJ, Prematta T, Craig TJ. Treatment of hereditary angioedema with plasma-derived C1 inhibitor. Ther Clin Risk Manag. 2008; 4:975-82. [PubMed 19209279]
6. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001; 161:2417-29. [PubMed 11700154]
7. Caliezi C, Wuillemin WA, Zeerleder S et al. C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Pharmacol Rev. 2000; 52:91-112. [PubMed 10699156]
8. US Food and Drug Administration. Briefing document from the blood products advisory committee. May 2, 2008. From FDA website (http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4355B2-2.pdf).
9. Levi M, Choi G, Picavet C et al. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol. 2006; 117:904-8. [PubMed 16630950]
10. Frank MM. 8. Hereditary angioedema. J Allergy Clin Immunol. 2008; 121:S398-401; quiz S419.
11. Bork K, Witzke G. Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. J Allergy Clin Immunol. 1989; 83:677-82. [PubMed 2926086]
12. Gompels MM, Lock RJ, Abinun M et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005; 139:379-94. [PubMed 15730382]
13. Bowen T, Cicardi M, Bork K et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol. 2008; 100 (Supp 2):S30-40.
14. Temiño VM, Peebles RS. The spectrum and treatment of angioedema. Am J Med. 2008; 121:282-6. [PubMed 18374684]
15. Frank MM, Jiang H. New therapies for hereditary angioedema: disease outlook changes dramatically. J Allergy Clin Immunol. 2008; 121:272-80. [PubMed 18206518]
16. Farkas H, Varga L, Széplaki G et al. Management of hereditary angioedema in pediatric patients. Pediatrics. 2007; 120:e713-22.
17. Horstick G, Berg O, Heimann A et al. Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects. Circulation. 2001; 104:3125-31. [PubMed 11748112]
18. Zuraw B, Busse P, White M et al. Efficacy and safety of long term prophylaxis with C1 inhibitor (C1INH) concentrate in patients with hereditary angioedema. J Allergy Clin Immunol. 2008; 21:S272, Abstract 1049.
19. Epstein TG, Bernstein JA. Current and emerging management options for hereditary angioedema in the US. Drugs. 2008; 68:2561-73.
20. ViroPharma: Personal communication.
More Cinryze resources
- Cinryze Prescribing Information (FDA)
- Cinryze Advanced Consumer (Micromedex) - Includes Dosage Information
- Cinryze MedFacts Consumer Leaflet (Wolters Kluwer)
- Cinryze Consumer Overview
- Berinert Prescribing Information (FDA)
- Berinert MedFacts Consumer Leaflet (Wolters Kluwer)
- Berinert Consumer Overview