Will a patient with a known allergy to Captopril (Angiotensin-Converting Enzyme inhibitor) also be allergic to Enalapril (Angiotensin-Converting Enzyme inhibitor)?

Cross-Allergy Between Captopril and Enalapril

A patient with a documented allergy to captopril may not necessarily be allergic to enalapril, but caution is strongly advised as cross-reactivity can occur, and enalapril is contraindicated in patients with a history of angioedema related to any ACE inhibitor. 1, 2

FDA-Mandated Contraindications

Both FDA drug labels explicitly address this issue:

• Enalapril is contraindicated in patients with a history of angioedema related to previous treatment with any angiotensin-converting enzyme inhibitor 1
• Captopril is contraindicated in patients who have experienced angioedema during therapy with any other ACE inhibitor 2

Type of Allergic Reaction Determines Cross-Reactivity Risk

Angioedema (Class Effect)

• Angioedema is a class-related adverse effect affecting all ACE inhibitors including captopril, enalapril, and lisinopril, occurring in <1% to 0.5% of patients 3, 4, 5
• This reaction can be life-threatening or fatal, with cases of complete airway obstruction and death documented 6, 7
• Angioedema occurs more frequently in Black patients and women 3
• If the captopril allergy was angioedema, enalapril is absolutely contraindicated 3, 1

Selective Hypersensitivity (Structure-Specific)

• Captopril is the only ACE inhibitor containing a sulfhydryl group, which can cause unique immunologic reactions 8
• Research demonstrates that selective allergy to captopril without cross-reactivity to enalapril and lisinopril is possible 8
• One case report documented a patient with positive patch tests to captopril but negative tests and successful oral challenges to both enalapril and lisinopril 8

Clinical Decision Algorithm

If the allergy was angioedema:

• Do not use enalapril or any other ACE inhibitor 3, 1, 2
• Consider an ARB as alternative therapy, though caution is advised as some patients develop angioedema with ARBs as well 3

If the allergy was a cutaneous reaction (rash, maculopapular eruption):

• This may represent selective captopril hypersensitivity related to its unique sulfhydryl group 8
• Patch testing can identify selective captopril allergy and demonstrate tolerance to other ACE inhibitors 8
• Enalapril may be tolerated, but should only be initiated under controlled conditions with close monitoring 8

If the allergy was cough:

• Cough affects up to 20% of patients on ACE inhibitors and is related to bradykinin accumulation, a class effect 3
• All ACE inhibitors including enalapril will likely cause the same reaction 3
• Switch to an ARB, which has a much lower incidence of cough 3

Critical Safety Considerations

• Early-onset adverse effects (within weeks) versus late-onset reactions (months to years after starting therapy) have both been documented with ACE inhibitors 5, 7
• Adverse effects such as rash, dysgeusia, neutropenia, and proteinuria were more common with early high-dose captopril but are less frequent with lower doses and are not typically seen with enalapril 4
• Hypotension, hyperkalemia, and renal impairment are pharmacologic effects common to all ACE inhibitors, not true allergies 3, 4

Bottom Line for Clinical Practice

The nature of the "allergy" is paramount. If angioedema occurred with captopril, enalapril is contraindicated by FDA labeling and clinical guidelines. If the reaction was a non-angioedema cutaneous response, selective captopril allergy is possible, and enalapril may be tolerated—but this requires formal allergy evaluation with patch testing before rechallenge. 3, 1, 2, 8