What is the treatment for lisinopril (Angiotensin-Converting Enzyme inhibitor) associated angioedema?

Treatment of Lisinopril-Associated Angioedema

The cornerstone of treatment for ACE inhibitor-associated angioedema is immediate discontinuation of the ACE inhibitor (lisinopril). 1

Initial Management

• Discontinue lisinopril immediately and permanently document the ACE inhibitor allergy in the patient's medical record 1, 2
• Closely monitor patients with oropharyngeal or laryngeal involvement in a medical facility capable of performing intubation or tracheostomy if necessary 2
• Consider elective intubation if signs of impending airway closure are present, with backup tracheostomy equipment available 2
• Be aware that airway anatomy may be distorted by angioedema, potentially requiring physicians highly skilled in airway management 2

Pharmacological Management

• Standard treatments for allergic reactions have limited efficacy in ACE inhibitor-induced angioedema: 1, 2

  • Antihistamines, corticosteroids, and epinephrine have not been shown to be reliably effective 1, 2
  • Despite limited evidence, the following medications are often administered:
    • IV methylprednisolone 125 mg 2
    • IV diphenhydramine 50 mg 2
    • Ranitidine 50 mg IV or famotidine 20 mg IV 2
    • If angioedema worsens despite above treatments, consider epinephrine (0.1%) 0.3 mL subcutaneously or by nebulizer 0.5 mL 2

• For severe cases, consider bradykinin pathway-targeted therapies: 1, 2

  • Icatibant (a selective bradykinin B2 receptor antagonist): 30 mg subcutaneously in the abdominal area; additional injections may be administered at 6-hour intervals (maximum 3 injections in 24 hours) 2
  • Fresh frozen plasma has shown efficacy in some cases, though controlled studies are lacking 1, 2
  • Plasma-derived C1 esterase inhibitor (20 IU/kg) has been used successfully in some cases 2

Observation and Follow-up

• The duration of observation should be based on severity and location of angioedema 2
• Be aware that the propensity to develop angioedema can continue for up to 6 weeks after discontinuation of the ACE inhibitor 2
• Avoid direct visualization of the airway unless necessary, as trauma from the procedure can worsen angioedema 2

Future Antihypertensive Selection

• After an episode of ACE inhibitor-induced angioedema, use extreme caution when considering an ARB as a replacement therapy 1, 3
• A meta-analysis found the risk of recurrent angioedema when switching from an ACE inhibitor to an ARB ranges from 2% to 17% 1, 3
• When deciding whether to use an ARB, carefully weigh the benefits of continuing renin-angiotensin system blockade against the risk of recurrent angioedema 3
• Consider alternative antihypertensive classes such as calcium channel blockers, which have not shown increased risk of angioedema after ACE inhibitor reactions 1, 3

Special Considerations

• African American patients (like the patient in 4), smokers, older individuals, and females are at higher risk for ACE inhibitor-induced angioedema 1, 2
• The mechanism involves impaired degradation of bradykinin, leading to increased plasma bradykinin levels 1, 2
• Angioedema can occur at any time during treatment - from the first dose to many years later, as demonstrated in a case where life-threatening angioedema occurred after 11 years on lisinopril 5
• Be aware that ACE inhibitor-induced angioedema can affect not only the face, lips, and tongue but also the intestines, presenting as abdominal pain and diarrhea 4