Pediatric Angioedema Medication

Treatment of urticaria-related angioedema is the same as that for urticaria.^[23] 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.

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.

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.

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).

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 inhibitor, human (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.

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.

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).

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. It is available as injectable solution, at 10 mg/mL per single-use vial.

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)

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

C1 esterase inhibitor, human (Berinert)

This agent is a serine proteinase inhibitor found in human blood that regulates activation of the 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.

This agent is indicated for acute laryngeal, abdominal, and facial angioedema attacks in adolescents and adults with HAE.