What is the management of angioedema caused by Lisinopril (Angiotensin-Converting Enzyme Inhibitor)?

From the Guidelines

Management of angioedema due to lisinopril requires immediate discontinuation of the medication and all other ACE inhibitors permanently. For acute management, assess airway patency first as severe cases may require intubation or emergency tracheostomy 1. The following steps can be taken:

• Administer epinephrine 0.3-0.5 mg IM (1:1000 solution) for severe reactions, though it may be less effective than in allergic angioedema
• Give antihistamines such as diphenhydramine 25-50 mg IV/PO and H2 blockers like famotidine 20 mg IV/PO to help with symptoms
• Corticosteroids (methylprednisolone 125 mg IV or prednisone 40-60 mg PO) may be used, though their benefit is primarily for preventing biphasic reactions
• In severe cases unresponsive to standard therapy, icatibant (30 mg SC) or C1 inhibitor concentrates may be considered 1
• Monitor the patient for at least 24 hours as symptoms typically resolve within this timeframe For future antihypertensive therapy, avoid all ACE inhibitors and consider alternatives such as angiotensin receptor blockers (though cross-reactivity occurs in about 10% of cases), calcium channel blockers, or thiazide diuretics 1. ACE inhibitor-induced angioedema occurs due to bradykinin accumulation rather than histamine release, explaining why traditional allergy medications may have limited effectiveness.

From the FDA Drug Label

1. 2 Angioedema and Anaphylactoid Reactions Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred

The management of angioedema due to lisinopril involves:

• Prompt discontinuation of lisinopril
• Appropriate therapy and monitoring until complete and sustained resolution of signs and symptoms of angioedema has occurred
• Close observation for patients with a history of airway surgery, as they are at higher risk of airway obstruction 2

From the Research

Management of Angioedema due to Lisinopril

• Angioedema associated with lisinopril use has been reported, with an incidence greater than that associated with captopril or enalapril 3.
• The condition typically presents with edema of the lips, buccal mucosa, and face, but can progress to involve the tongue and airway 3, 4.
• Standard management includes discontinuation of lisinopril and treatment with antihistamines, such as diphenhydramine, and corticosteroids 3, 5.

Pharmacotherapy for ACEI-Induced Angioedema

• A systematic review of pharmacotherapy for ACEI-induced angioedema found that bradykinin antagonists, kallikrein inhibitors, and C1 inhibitor replacement may be effective in treating the condition, but further study is needed to establish their efficacy 5.
• Icatibant, a bradykinin B2 receptor antagonist, has been shown to improve symptoms more rapidly than corticosteroids and antihistamines in one study 5.
• C1 inhibitors, such as C1 esterase inhibitor, have been used to treat ACEI-induced angioedema and may reduce mechanical ventilation time 4, 6.

Risk Factors and Treatment Considerations

• Certain populations, including blacks, women, and smokers, are at increased risk for ACEI-induced angioedema 7.
• Angioedema may occur at any time during treatment with ACEIs and may continue after the medication is discontinued 7.
• Treatment with C1 inhibitors, such as C1 esterase inhibitor, may be considered for patients who remain symptomatic after initial interventions and are at risk of a compromised airway 6.