that youngsters [20:<20 units/kg; efficacy of 10-unit/kg dose not established. 21 22 Cautions for C1-Esterase Inhibitor (Human) Contraindications Known life-threatening hypersensitivity (e.g., anaphylaxis) to C1-esterase inhibitor (human) or any ingredient in the formulation. 1 21 Warnings/Precautions Warnings Thrombotic Events Risk of thromboembolic events (e.g., MI, cerebrovascular accident, DVT, PE); reported in association with recommended as well as with higher than recommended (e.g., ≥100 units/kg) doses. 1 17 21 28 Closely monitor patients with known risk factors for thrombosis. 1 21 Risk of Transmissible Agents in Plasma-derived Preparations Potential vehicle for transmission of human viruses (e.g., HIV, hepatitis A virus [HAV], HBV, HCV, parvovirus B19) or other infectious agents (e.g., Creutzfeldt-Jakob disease [CJD]). 1 9 12 13 21 Risk substantially reduced with current donor screening practices and viral inactivating procedures; however, possibility of disease transmission still exists. 1 12 15 19 21 Although cases of suspected viral transmission (including HCV) have been reported with use of Berinert outside the US, manufacturer states no causal relationship to the drug has been established since introduction of a pasteurization step in 1985. 21 Weigh risks of viral infection against benefits of therapy. 1 12 21 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. 1 21 Laryngeal Attacks Because of potential for airway obstruction, patients who self-administer C1-esterase inhibitor (human) for treatment of a laryngeal attack should seek immediate medical attention in an appropriate healthcare facility after the drug is administered. 21 Immunogenicity Potential for immunogenicity with use of all therapeutic proteins, including C1-esterase inhibitor (human). 1 Development of noninhibitory antibodies to C1-esterase inhibitor (human) reported in clinical trials; however, clinically important effects not observed. 1 38 39 Sensitivity Reactions Hypersensitivity Risk of severe hypersensitivity reactions (e.g., hives, urticaria, chest tightness, wheezing, hypotension, anaphylaxis). 1 21 If hypersensitivity occurs, discontinue drug immediately and initiate appropriate treatment. 1 21 Because symptoms of hypersensitivity can resemble acute attacks of hereditary angioedema, carefully consider treatment method. 1 21 Epinephrine should be available for immediate use. 1 21 Specific Populations Pregnancy Category C. 1 21 Lactation Not known whether C1-esterase inhibitor (human) is distributed into milk. 1 21 Use with caution and only if clearly needed. 1 21 Pediatric Use Safety and efficacy of Cinryze not established in neonates, infants, and children> <13 years of age; use in adolescents 13 18 years of age supported by data from approval study. 1 20 Safety and efficacy of Berinert not established in pediatric patients 12 years of age, although used successfully for the treatment of acute HAE attacks in a limited number of children as young as 6 years of age. 21 25 37 Geriatric Use Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. 1 21 Hepatic Impairment Pharmacokinetics not evaluated in patients with hepatic impairment. 1 21 Renal Impairment Pharmacokinetics not evaluated in patients with renal impairment. 1 21 Common Adverse Effects Headache, 1 21 22 33 nausea, 1 21 22 rash, 1 vomiting, 1 22 dysgeusia, 21 abdominal pain. 21 22 33 Interactions for C1-Esterase Inhibitor (Human) No formal drug interaction studies to date. 1 21 C1-Esterase Inhibitor (Human) Pharmacokinetics Absorption Onset 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 Plasma Concentrations Peak plasma concentrations attained in approximately 4 hours following a single 1000-unit dose of Cinryze . 1 8 Distribution Extent Not known whether C1-esterase inhibitor is distributed into milk. 1 Elimination Half-life Cinryze : Mean half-life about 56 hours (range 11 108 hours) following a single 1000-unit dose in asymptomatic patients. 1 8 Berinert : Following administration of single doses (500 1500 units) in patients with mild to severe HAE, half-life approximately 18 hours in adults and 17 hours in pediatric patients 6 13 years of age. 21 Difference in half-life observed between Cinryze and Berinert may be due to differences in patient populations evaluated (e.g., asymptomatic versus symptomatic). 34 Special Populations Limited data on Berinert suggest that half-life of C1-esterase inhibitor (human) may be decreased and clearance increased in pediatric patients> <12 years of age compared with adults; clinical importance of such findings not known. 21 Stability Storage Parenteral Powder for Injection 2 25°C; do not freeze. 1 21 Store in original container and protect from light. 1 21 May store reconstituted solutions at room temperature for up to 3 hours (Cinryze ) or up to 8 hours (Berinert ); do not refrigerate or freeze. 1 21 Actions 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 21 Also plays a role in the fibrinolytic system. 1 2 6 8 12 21 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 21 Blocks both the spontaneous activation of C1 complement and formation of activated C1 complement, suppressing the classical complement pathway. 1 6 7 12 21 Also exhibits inhibitory effects on plasmin. 4 11 12 Binds to and forms irreversible complexes with target protease; the complexes are then inactivated and removed from circulation. 1 6 7 8 11 21 Preparation of highly purified C1-esterase inhibitor derived from pooled human plasma. 1 8 19 21 Undergoes a series of viral reduction steps (e.g., pasteurization, precipitation, nanofiltration, chromatography) to reduce risk of viral transmission. 1 8 19 21 Advice to Patients Importance of discussing potential risks and benefits of therapy with the patient prior to prescribing or administering the drug. 1 21 Importance of clinicians providing clear instructions and training on proper IV administration technique to patients self-administering C1-esterase inhibitor (human). 21 Advise patients to record the lot number of the C1-esterase inhibitor (human) vial used each time they self-administer the drug. 1 21 Importance of patients not starting self-administration if an HAE attack has progressed to a point where the patient or caregiver is unable to successfully prepare or administer the drug. 21 After self-administering the drug to treat an acute laryngeal attack of HAE, importance of seeking immediate medical attention in an appropriate healthcare facility because of the potential for airway obstruction during such attacks. 21 After self-administering the drug to treat a suspected abdominal HAE attack, importance of contacting clinician to rule out the possibility of other potentially serious causes. 21 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 21 Advise patient that current donor screening and viral inactivating procedures have reduced, but not completely eliminated, the risk of disease transmission. 1 Importance of discontinuing therapy and immediately informing clinician if any signs or symptoms of hypersensitivity (e.g., rash, hives, chest tightness, wheezing, hypotension, anaphylaxis) occur. 1 21 Risk of thrombotic events; advise patients to immediately report any signs and symptoms of thrombosis (e.g., new-onset swelling and pain in the limbs or abdomen; new-onset chest pain; shortness of breath; loss of sensation or motor ability; altered consciousness, vision, or speech). 21 Advise patients to bring an adequate supply of C1-esterase inhibitor (human) while traveling and to consult a clinician prior to travel. 1 21 Advise patients to bring their drug with them when visiting a healthcare provider or facility for an acute HAE attack. 21 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 21 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. 1 21 Importance of informing patients of other important precautionary information. 1 21 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. C1-esterase Inhibitor Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV infusion 500 units Berinert CSL Behring Cinryze Viro Pharma AHFS DI Essentials. Copyright 2017, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. VioPharma. Cinryze (C1 inhibitor, human) prescribing information. Exton, PA; 2012 Nov. 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. 21. CSL Behring. Berinert (C1 esterase inhibitor, human) prescribing information. Kankakee, IL; 2012 July. 22. 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; 124:801-8. [PubMed 19767078] 23. Food and Drug Administration. Summary Basis for Regulatory Action: B:A Supplement#STN 125287/110. From FDA website. 24. Thomas MC, Shah S. New treatment options for acute edema attacks caused by hereditary angioedema. Am J Health Syst Pharm . 2011; 68:2129-38. [PubMed 22058099] 25. Farkas H, Csuka D, Zotter Z et al. Treatment of attacks with plasma-derived C1-inhibitor concentrate in pediatric hereditary angioedema patients. J Allergy Clin Immunol . 2013; 131:909-11. [PubMed 23063583] 26. Lang DM, Aberer W, Bernstein JA et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol . 2012; 109:395-402. [PubMed 23176876] 27. 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; 131:1491-3. [PubMed 23726531] 28. Gandhi PK, Gentry WM, Bottorff MB. Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database. Pharmacotherapy . 2012; 32:902-9. [PubMed 23033229] 29. Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet . 2012; 379:474-81. [PubMed 22305226] 30. Zuraw BL, Busse PJ, White M et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med . 2010; 363:513-22. [PubMed 20818886] 31. Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med . 1996; 334:1630-4. [PubMed 8628358] 32. . Three new drugs for hereditary angioedema. Med Lett Drugs Ther . 2010; 52:66-7. [PubMed 20724964] 33. Wasserman RL, Levy RJ, Bewtra AK et al. Prospective study of C1 esterase inhibitor in the treatment of successive acute abdominal and facial hereditary angioedema attacks. Ann Allergy Asthma Immunol . 2011; 106:62-8. [PubMed 21195947] 34. Bernstein JA, Ritchie B, Levy RJ et al. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol . 2010; 105:149-54. [PubMed 20674826] 35. Bork K, Barnstedt SE. Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with hereditary angioedema. Arch Intern Med . 2001; 161:714-8. [PubMed 11231704] 36. Craig T, Aygören-Pürsün E, Bork K et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J . 2012; 5:182-99. [PubMed 23282420] 37. Schneider L, Hurewitz D, Wasserman R et al. C1-INH concentrate for treatment of acute hereditary angioedema: a pediatric cohort from the I.M.P.A.C.T. studies. Pediatr Allergy Immunol . 2013; 24:54-60. [PubMed 23173714] 38. Craig TJ, Bewtra AK, Bahna SL et al. C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study. Allergy . 2011; 66:1604-11. [PubMed 21884533] 39. Craig TJ, Bewtra AK, Hurewitz D et al. Treatment response after repeated administration of C1 esterase inhibitor for successive acute hereditary angioedema attacks. Allergy Asthma Proc . 2012 Jul-Aug; 33:354-61. Next Interactions Print this page Add to My Med List More about C1 esterase inhibitor (human) Side Effects During Pregnancy or Breastfeeding Dosage Information Drug Interactions Support Group En Español 5 Reviews Add your own review/rating Drug class: miscellaneous coagulation modifiers Consumer resources Complement C1 esterase inhibitor ... +5 more Professional resources C1-Esterase Inhibitor (Recombinant) (AHFS Monograph) C1 Inhibitor (Human) (Wolters Kluwer) Other brands: Berinert , Cinryze Related treatment guides Hereditary Angioedema> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Drug Class Miscellaneous coagulation modifiers Related Drugs Hereditary Angioedema Firazyr , Berinert , Haegarda , Ruconest , Cinryze , icatibant , Kalbitor , ecallantide , C1 esterase inhibitor (human) , conestat alfa , More... 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