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Pediatric Angioedema Medication

  • Author: Shih-Wen Huang, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Jul 21, 2014
 

Medication Summary

Treatment of urticaria-related angioedema is the same as that for urticaria.[35] Drug therapy for hereditary angioedema (HAE) may be preventive or for the treatment of an acute attack. Few pediatric cases have been reported. Minor episodes of subepithelial swelling need no treatment, but patients with edema of the face and neck should be closely observed for spreading and for signs of airway involvement. Airway involvement can be a true medical emergency in this disorder.

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Androgens

Class Summary

Oral androgens have provided the most successful preventive therapy. Synthetic attenuated androgens (eg, danazol, oxandrolone) taken prophylactically increase the serum concentration of C1 inhibitor (C1INH), presumably by enhancing the function of the C1INH gene (SERPING1). When danazol is used prophylactically in adolescents or preadolescents, the concentration of C1INH and C4 are increased in the plasma.

Danazol

 

This agent increases levels of C4 component of complement and reduces attacks associated with angioedema. In HAE, danazol increases level of deficient C1 esterase inhibitor.

Oxymetholone (Anadrol-50)

 

Oxymetholone is an anabolic and androgenic derivative of testosterone formulated for oral administration. It is a synthetic attenuated androgen with relatively few adverse effects.

Oxandrolone (Oxandrin)

 

Oxandrolone is considered one of the safer anabolic steroids available. It has gained orphan drug status to treat Turner syndrome, constitutional delayed growth or puberty of boys, and alcoholic hepatitis, and has recently been used to treat AIDS-wasting syndrome. Hepatotoxicity (more commonly observed in the group receiving 17 alpha alkylated androgen) has not been observed. Oxandrolone may prevent HAE in cases where other androgens were ineffective.

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Antifibrinolytic Agents

Class Summary

These agents have been successfully used as preventive therapy. The effect may depend on physiologic or pathologic enhancement of plasminogen activation in blood, which may promote activation of C1INH.

Aminocaproic acid (Amicar)

 

Aminocaproic acid is an antifibrinolytic agent used for immediate short-term treatment of angioedema. It inhibits fibrinolysis via the inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. It is widely distributed. The half-life is 1-2 hours. For the inhibition of angioedema, several days of treatment may be required. Hepatic metabolism is minimal. This agent can be used orally or intravenously.

It is thought to prevent extensive edema formation after the onset of an attack. Even if the patient has bouts of intestinal edema, symptoms are markedly ameliorated.

Tranexamic acid (Cyklokapron)

 

Tranexamic acid is used for immediate short-term treatment. It inhibits fibrinolysis by displacing plasminogen from fibrin. It also prevents extensive edema formation and helps ameliorate intestinal symptoms.

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Blood Products

Class Summary

Fresh frozen plasma (FFP) is used for treatment of acute attacks. Replacement therapy is logical in the case of an ongoing attack. Numerous reports indicate that FFP may relieve an episode of edema; on the other hand, symptoms may worsen because FFP also contains sufficient substrate to the enzyme that is to be replaced.

The differences in response to this treatment probably result from differences between the onset of symptoms and the time of an attack. When patient arrives at the emergency department (ED), the attack has probably been underway for a number of hours or more than a day. Some believe that early administration of FFP may worsen edema.

Fresh frozen plasma (FFP)

 

Plasma is the fluid compartment of blood containing many components essential to the complement cascade (ie, C1 esterase inhibitor).

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Sympathomimetic Agents

Class Summary

These agents directly or indirectly stimulate adrenergic receptors. They are used as supportive emergency treatment for airway edema.

Epinephrine (Adrenalin)

 

An oropharyngeal spray of 1:1000 racemic epinephrine helps reduce edema, especially in the upper airway (eg, laryngeal edema).

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Kallikrein Inhibitor

Class Summary

This agent elicits specific kallikrein inhibitor activity resulting in bradykinin reduction. It is useful for treating acute episodic attacks. The 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.

Ecallantide (Kalbitor)

 

A human plasma kallikrein inhibitor, ecallantide binds to plasma kallikrein and blocks its binding site. It reduces conversion of kininogen to bradykinin. Ecallantide is indicated for acute attacks of HAE in adults and children aged 12 years or older. It is available as injectable solution, at 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). Safety and efficacy has not been established in patients younger than 18 years.

Icatibant (Firazyr)

 

Icatibant is a bradykinin B2 receptor antagonist indicated for acute attacks of HAE.

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Serine Proteinase Inhibitors (serpins)

Class Summary

These agents recently received approval from the US Food and Drug Administration (FDA) for use in HAE. They are derived from human plasma.

C1 esterase inhibitor, human (Berinert, Cinryze)

 

C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). It regulates activation of pathway for complement and intrinsic coagulation, as well as the fibrinolytic system. It binds to and neutralizes substrates that activate these systems, thereby suppressing activity.

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 HAE.

C1-INH some of the missing protein, but its 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.

C1 esterase inhibitor recombinant (Ruconest)

 

Recombinant C1 esterase inhibitor is from the milk of genetically modified (transgenic) rabbits. It restores the level of functional C1-esterase inhibitor in a patient's plasma, thereby treating the acute attack of swelling. It is indicated for adolescents and adults to treat acute attacks of HAE. Efficacy for treatment of laryngeal attack was not established.

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Contributor Information and Disclosures
Author

Shih-Wen Huang, MD Professor Emeritus of Pulmonology and Allergy, Department of Pediatrics, University of Florida College of Medicine

Shih-Wen Huang, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

C Lucy Park MD, Head, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago College of Medicine

C Lucy Park is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Medical Association, Chicago Medical Society, Clinical Immunology Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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The mechanism of angioedema resulting from C1-esterase inhibitor deficiency.
Angioedema secondary to ACE inhibitors
 
 
 
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