140th [84:<84 kg; 4200 units in patients weighing ≥84 kg. 1 May administer a second dose if attack symptoms persist. 1 Prescribing Limits Pediatric Patients Hereditary Angioedema Treatment of Acute Angioedema Attacks IV Adolescents 13 17 years of age: Maximum 4200 units per dose; do not exceed 2 doses within a 24-hour period. 1 Adults Hereditary Angioedema Treatment of Acute Angioedema Attacks IV Maximum 4200 units per dose; do not exceed 2 doses within a 24-hour period. 1 Cautions for C1-Esterase Inhibitor (Recombinant) Contraindications Known hypersensitivity to rabbits or rabbit-derived products. 1 16 Known life-threatening immediate hypersensitivity, including anaphylaxis, to C1-esterase inhibitor preparations. 1 Warnings/Precautions Thrombotic Events Risk of thromboembolic events. 1 28 Reported with plasma-derived C1-esterase inhibitor at recommended doses in patients with underlying risk factors (e.g., presence of indwelling venous catheter/access device, history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, immobility). 1 28 Clinical studies to date have not suggested an increased thrombotic risk with C1-esterase inhibitor (recombinant). 15 22 32 37 Closely monitor patients with known risk factors for thromboembolism. 1 Immunogenicity Potential for immunogenicity with use of all therapeutic proteins, including C1-esterase inhibitor (recombinant). 1 Development of non-neutralizing antibodies to C1-esterase inhibitor (recombinant) reported in clinical trials; however, clinically important effects not observed. 1 37 Sensitivity Reactions Hypersensitivity Risk of severe hypersensitivity reactions (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis). 1 (See Contraindications under Cautions.) Anaphylaxis was reported in an individual with preexisting allergy to rabbit protein. 1 37 If hypersensitivity occurs, discontinue drug immediately and initiate appropriate treatment. 1 Because symptoms of hypersensitivity can resemble acute attacks of HAE, carefully consider treatment method. 1 Specific Populations Pregnancy Category B. 1 No adequate and well-controlled studies in pregnant women. 1 30 Animal studies suggest a possibility of adverse embryofetal effects. 1 Lactation Not known whether C1-esterase inhibitor (recombinant) is distributed into human milk. 1 Use with caution. 1 Pediatric Use Safety and efficacy not established in pediatric patients> <13 years of age; use of the drug in adolescents 13 17 years of age is supported by data from approval studies. 1 25 Geriatric Use Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger patients. 1 Hepatic Impairment Pharmacokinetics not evaluated in patients with hepatic impairment. 1 Renal Impairment Pharmacokinetics not evaluated in patients with renal impairment. 1 Common Adverse Effects Headache, 17 18 20 21 32 nausea, 21 32 diarrhea. 18 21 32 Interactions for C1-Esterase Inhibitor (Recombinant) No formal drug interaction studies to date. 1 9 C1-Esterase Inhibitor (Recombinant) Pharmacokinetics Absorption Plasma Concentrations Peak plasma concentrations attained in approximately 0.3 hours following a single 50-unit/kg dose in asymptomatic patients. 1 32 Distribution Extent Not known whether distributed into human milk. 1 Elimination Half-life Approximately 2.5 hours following a 50-unit/kg dose in asymptomatic patients. 1 32 Exhibits nonlinear clearance. 1 Elimination half-life has been reported to be shorter than that of plasma-derived C1-esterase inhibitor due to differences in glycosylation. 15 22 31 34 Stability Storage Parenteral Powder for Injection 2 25°C; do not freeze. 1 Store in original container and protect from light. 1 May store reconstituted solutions at 2 8°C for up to 8 hours; do not freeze. 1 Actions Serine protease inhibitor that principally regulates the activation of the complement and intrinsic coagulation (e.g., contact system) pathways. 1 2 6 7 8 10 12 19 22 23 31 34 Also plays a role in the fibrinolytic system. 2 6 10 12 14 19 31 34 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 6 7 8 9 10 12 13 32 33 Blocks both the spontaneous activation of C1 complement and formation of activated C1 complement, suppressing the classical complement pathway. 1 6 7 12 Also exhibits inhibitory effects on plasmin. 8 12 23 Binds to and forms irreversible complexes with target protease, which are then inactivated and removed from circulation. 1 6 7 9 22 32 Biosynthetic (recombinant DNA origin) preparation of human C1-esterase inhibitor produced from the milk of transgenic (genetically modified) rabbits. 1 37 Undergoes a series of viral reduction steps (e.g., pasteurization, precipitation, nanofiltration, chromatography) to reduce risk of viral transmission. 1 8 15 37 Structurally and functionally similar to plasma-derived C1-esterase inhibitor. 1 8 32 Advice to Patients Importance of discussing potential risks and benefits of therapy with the patient prior to prescribing or administering the drug. 1 Importance of instructing patients to read the manufacturer's product information and instructions for use. 1 Importance of patients immediately informing a clinician if any signs or symptoms of hypersensitivity (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis) occur during or after administration of C1-esterase inhibitor (recombinant). 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.) 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 (Recombinant) Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV use 2100 units Ruconest Salix AHFS DI Essentials. Copyright 2017, Selected Revisions January 29, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Salix Pharmaceuticals, Inc. Ruconest (C1 inhibitor [recombinant]) prescribing information. Raleigh, NC; 2015 Feb. 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. From FDA web site. 4. ViroPharma. Cinryze (C1 inhibitor, human) prescribing information. Exton, PA; 2014 Feb. 5. CSL Behring. Berinert (C1 esterase inhibitor, human) prescribing information. Kankakee, IL; 2015 Feb. 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. Cardona LP, Bellfill RL, Caus JM. Recent developments in the treatment of acute abdominal and facial attacks of hereditary angioedema: focus on human C1 esterase inhibitor. Appl Clin Genet . 2010; 3:133-46. [PubMed 23776358] 9. Cruz MP. Conestat alfa (ruconest): first recombinant c1 esterase inhibitor for the treatment of acute attacks in patients with hereditary angioedema. P T . 2015; 40:109-14. [PubMed 25673959] 10. Frank MM. 8. Hereditary angioedema. J Allergy Clin Immunol . 2008; 121:S398-401; quiz S419. 11. Zuraw BL, Banerji A, Bernstein JA et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract . 2013 Sep-Oct; 1:458-67. 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. Riedl M. Recombinant Human C1 Esterase Inhibitor in the Management of Hereditary Angioedema. Clin Drug Investig . 2015; 35:407-17. [PubMed 26091744] 16. MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol . 2014; 25:420-7. [PubMed 24313851] 17. Riedl MA, Bernstein JA, Li H et al. Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol . 2014; 112:163-169.e1. [PubMed 24468257] 18. Zuraw B, Cicardi M, Levy RJ et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol . 2010; 126:821-827.e14. [PubMed 20920772] 19. Epstein TG, Bernstein JA. Current and emerging management options for hereditary angioedema in the US. Drugs . 2008; 68:2561-73. [PubMed 19093699] 20. Riedl MA, Levy RJ, Suez D et al. Efficacy and safety of recombinant C1 inhibitor for the treatment of hereditary angioedema attacks: a North American open-label study. Ann Allergy Asthma Immunol . 2013; 110:295-9. [PubMed 23535096] 21. Moldovan D, Reshef A, Fabiani J et al. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy . 2012; 42:929-35. [PubMed 22909164] 22. Plosker GL. Recombinant human c1 inhibitor (conestat alfa): in the treatment of angioedema attacks in hereditary angioedema. BioDrugs . 2012; 26:315-23. [PubMed 22946752] 23. Relan A, Bakhtiari K, van Amersfoort ES et al. Recombinant C1-inhibitor: effects on coagulation and fibrinolysis in patients with hereditary angioedema. BioDrugs . 2012; 26:43-52. [PubMed 22171564] 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. Caballero T, Farkas H, Bouillet L et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol . 2012; 129:308-20. [PubMed 22197274] 31. Sabharwal G, Craig T. Recombinant human C1 esterase inhibitor for the treatment of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE). Expert Rev Clin Immunol . 2015; 11:319-27. [PubMed 25669442] 32. Moldovan D, Bernstein JA, Cicardi M. Recombinant replacement therapy for hereditary angioedema due to C1 inhibitor deficiency. Immunotherapy . 2015; :1-14. 33. Varga L, Farkas H. rhC1INH: a new drug for the treatment of attacks in hereditary angioedema caused by C1-inhibitor deficiency. Expert Rev Clin Immunol . 2011; 7:143-53. [PubMed 21426252] 34. Davis B, Bernstein JA. Conestat alfa for the treatment of angioedema attacks. Ther Clin Risk Manag . 2011; 7:265-73. [PubMed 21753889] 35. Bhardwaj N, Craig TJ. Treatment of hereditary angioedema: a review (CME). Transfusion . 2014; 54:2989-96; quiz 2988. [PubMed 24735226] 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. US Food and Drug Administration. Summary Basis for Regulatory Action: BLA# BL-125495/0. From FDA website. 38. van Doorn MB, Burggraaf J, van Dam T et al. A phase I study of recombinant human C1 inhibitor in asymptomatic patients with hereditary angioedema. J Allergy Clin Immunol . 2005; 116:876-83. [PubMed 16210064] 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 (Human) (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 , Cinryze , Ruconest , icatibant , Kalbitor , ecallantide , C1 esterase inhibitor (human) , conestat alfa , More... 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