Hereditary Angioedema Medication

  • Author: Michael M Frank, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Feb 8, 2012
 

Medication Summary

The goals of pharmacotherapy for hereditary angioedema (HAE) are to reduce morbidity and to prevent complications. Medication may be used for acute or preventive treatment.

In Europe, purified C1 inhibitor (C1-INH) has been available for treatment of acute attacks for decades, but it has not been available in the United States until recently.[2, 38, 39] In October 2008, the US Food and Drug Administration (FDA) approved the use of C1-INH (Cinryze) at a dose of 1000 units IV 2-3 times/week for prophylaxis to prevent attacks. In October 2009, the FDA approved C1-INH (Berinert) at a dose of 20 units/kg IV for the treatment of acute abdominal and facial angioedema attacks in adolescents and adults with HAE.[21] In January 2012, an additional indication for laryngeal angioedema was approved by the FDA. Berinert is also approved for patient self-administration after proper training by a healthcare professional.

In December 2009, ecallantide (Kalbitor), a kallikrein inhibitor, at a dose of 30 mg SC was approved for the treatment of acute attacks.

In August 2011, icatibant (Firazyr), a selective bradykinin B2 receptor antagonist, was approved for treatment of acute attacks of HAE in adults at a dose of 30 mg SC in the abdominal area.

Purified C1-INH, fresh frozen plasma (FFP), or attenuated androgen is given prophylactically prior to surgery.

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Blood Products

Class Summary

These agents are used to improve the clinical aspects of the disease.

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Fresh frozen plasma

 

Infuse prior to airway manipulation (eg, dental extraction) to prevent angioedema. Administering 2 units of FFP sustains complement control and prevents development of angioedema. Improved screening programs greatly reduce risk of hepatitis. FFP is not recommended for treatment of acute attacks.

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Androgens and Androgen Derivatives

Class Summary

Some agents in this class may increase levels of C1 inhibitor and C4 component of complement.[40, 41, 42]

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Danazol (Danocrine)

 

Danazol reduces the frequency of attacks in most patients, especially those involving the airway. For prophylaxis, the dose is adjusted to lowest dose that controls symptoms.

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C1-Inhibitor Concentrates

Class Summary

These concentrates are used in the acute treatment of angioedema. They have recently been approved by the US FDA for routine prophylaxis against angioedema attacks and as treatment for acute attacks.

C1-inhibitor, human (Cinryze) and C1 esterase inhibitor, human (Berinert) are the same plasma protein, although for historical reasons they have been given different names. The methods of purification are somewhat different.

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C1-inhibitor, human (Cinryze)

 

C1-INH is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). It regulates activation of the pathway for complement and intrinsic coagulation, and it also regulates the fibrinolytic system.

This agent is available as a sterile, lyophilized preparation derived from human plasma. Specific activity is 4-9 U/mg protein. One unit corresponds to the mean quantity of C1 inhibitor present in 1 mL of normal fresh plasma. It is indicated for routine prophylaxis against angioedema attacks in adolescents and adults with hereditary angioedema.

C1-INH some of the missing protein, but the half-life in the circulation is short. Approved use is 1000 units biweekly with the possibility of a third dose of 1000 units/wk if needed. Although FDA approval is for prophylaxis only at this time, this agent has been available for treatment of acute attacks in Europe for decades and has an excellent safety profile.

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C1 esterase inhibitor, human (Berinert)

 

This agent is a serine proteinase inhibitor found in human blood that regulates activation of the kinin system, complement pathway, intrinsic coagulation system, and fibrinolytic system. It binds to and neutralizes substrates that activate these systems, thereby suppressing activity. It is available as a pasteurized, lyophilized preparation derived from purified human plasma. One unit corresponds to the mean quantity of C1 inhibitor present in 1 mL of normal fresh plasma. C1 esterase inhibitor is indicated for acute laryngeal, abdominal, and facial angioedema attacks in adolescents and adults with HAE.

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Kallikrein Inhibitor

Class Summary

This agent has specific kallikrein inhibitor activity resulting in bradykinin reduction. It is useful for treating acute episodic attacks. Package insert carries a black box warning because a small subset of patients may have anaphylactic reactions to the drug. It must be administered by medical personnel capable of treating anaphylaxis.

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Ecallantide (Kalbitor)

 

A human plasma kallikrein inhibitor, ecallantide binds to plasma kallikrein and blocks its binding site. It reduces conversion of kininogen to bradykinin. This agent is indicated for acute attacks of HAE. It is available as an injectable solution; 10 mg/mL per single-use vial.

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Bradykinin Receptor Antagonists

Class Summary

Bradykinin receptor antagonists such as icatibant inhibit bradykinin from binding the B2 receptor and thereby treat the clinical symptoms of an acute attack. Recommended dose of icatibant is 30 mg SC in the abdominal area. It is available as a single-use, prefilled syringe, which delivers a dose of 30 mg (10 mg/mL).

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Icatibant (Firazyr)

 

Bradykinin B2 receptor antagonist indicated for acute attacks of hereditary angioedema (HAE).

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Antifibrinolytic Agents

Class Summary

These agents act through the inhibition of plasmin. They are potent inhibitors of fibrinolysis and can reverse states that are associated with excessive fibrinolysis.[12]

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Aminocaproic acid (Amicar)

 

Aminocaproic acid is a lysine analog that inhibits fibrinolysis via inhibition of plasminogen activator substances; to a lesser degree, through antiplasmin activity.

It is widely distributed. Half-life is 1-2 h. For inhibition of angioedema, several days of treatment may be required. Hepatic metabolism is minimal. This agent can be used PO/IV.

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Tranexamic acid (Cyklokapron)

 

An alternative to aminocaproic acid, tranexamic acid inhibits fibrinolysis by displacing plasminogen from fibrin.

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Contributor Information and Disclosures
Author

Michael M Frank, MD  Samuel L Katz Professor of Pediatrics, Professor of Medicine and Immunology, Duke University School of Medicine, Duke University Medical Center

Michael M Frank, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, and Society for Pediatric Research

Disclosure: ViroPharma Consulting fee research; Shire Consulting fee Consulting; CSL Behring Consulting fee Consulting; Dyax Consulting fee Consulting

Coauthor(s)

Warren R Heymann, MD  Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Amanda T Moon, MD  Resident Physician, Department of Dermatology, University of Rochester, Strong Memorial Hospital

Amanda T Moon, MD, is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen Rosenfeld, MD  Professor Emeritus, Department of Medicine, Allergy, Immunology and Rheumatology Unit, University of Rochester School of Medicine and Dentistry

Stephen Rosenfeld, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American Federation for Clinical Research, Clinical Immunology Society, and Medical Society of the State of New York

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Paul Krusinski, MD  Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting fee Consulting; sunovian Consulting fee Consulting; dey Honoraria Review panel membership

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Kathleen M Rossy, MD,to the development and writing of a source article.

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