No, lisinopril should NOT be used if allergic to enalapril
If a patient has experienced angioedema with enalapril, all ACE inhibitors including lisinopril are absolutely contraindicated for life. This is a class effect, and the risk of recurrent, potentially fatal angioedema makes switching between ACE inhibitors unacceptable.
Why All ACE Inhibitors Are Contraindicated
Both enalapril and lisinopril FDA labels explicitly state that these drugs are contraindicated in patients with "a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor" 1, 2. The 2013 ACC/AHA Heart Failure guidelines reinforce this, stating that "angioedema occurs in <1% of patients who take an ACE inhibitor...Because its occurrence may be life-threatening, clinical suspicion of this reaction justifies the subsequent avoidance of all ACE inhibitors for the lifetime of the patient. ACE inhibitors should not be initiated in any patient with a history of angioedema" 3.
The mechanism is identical across all ACE inhibitors: they inhibit the breakdown of bradykinin, which directly or indirectly causes angioedema 4, 5. This is not drug-specific but rather a class effect inherent to ACE inhibition itself.
The Alternative: ARBs (With Caution)
For patients with ACE inhibitor-induced angioedema, angiotensin receptor blockers (ARBs) are the recommended alternative, though they must be used with caution. The 2017 ACC/AHA guidelines state: "Patients intolerant to ACE inhibitors because of cough or angioedema should be started on ARBs" 4.
Important Caveats About ARBs:
- There is a 2-17% risk of recurrent angioedema when switching from an ACE inhibitor to an ARB in patients who experienced ACE inhibitor-induced angioedema 6
- Wait at least 6 weeks after discontinuing the ACE inhibitor before starting an ARB 7
- The 2018 ACC/AHA Hypertension guidelines note: "Patients with a history of angioedema with an ACE inhibitor can receive an ARB beginning 6 weeks after ACE inhibitor is discontinued" 7
- Despite this risk, "most patients who have experienced ACE-I–induced angioedema can safely use ARBs without recurrence of angioedema" 6
If the Allergy is NOT Angioedema
If the "allergy" to enalapril was something other than angioedema (such as cough, rash, or other non-life-threatening reactions), the situation differs:
- For cough: This is also a class effect due to bradykinin accumulation. Switching to lisinopril will likely reproduce the cough. ARBs are preferred 3, 8, 9
- For other reactions (rash, dysgeusia): These were more common with early high-dose captopril and are less frequent with other ACE inhibitors at recommended doses 10. However, cross-reactivity is still possible
Clinical Bottom Line
The term "allergic to enalapril" must be clarified immediately:
- If angioedema occurred: Never use any ACE inhibitor again. Use an ARB instead (waiting 6 weeks after stopping enalapril)
- If cough occurred: Switching to lisinopril is futile; use an ARB
- If other reactions occurred: Consider ARB as safer alternative, though some ACE inhibitors might theoretically be tolerated
The safest approach is to avoid all ACE inhibitors and use an ARB when a patient reports any significant adverse reaction to an ACE inhibitor, particularly given that ARBs have comparable mortality and morbidity benefits in heart failure and post-MI patients 3, 4, 11.