If a patient has a known allergy to captopril (Angiotensin-Converting Enzyme (ACE) inhibitor), will they also be allergic to enalapril (ACE inhibitor)?

Cross-Reactivity Between Captopril and Enalapril

If you have a true allergy to captopril, you will NOT necessarily be allergic to enalapril—the type of reaction determines cross-reactivity risk.

Understanding ACE Inhibitor Hypersensitivity Patterns

The critical distinction lies in whether your captopril reaction was:

1. Angioedema (Life-Threatening Swelling)

• All ACE inhibitors are absolutely contraindicated for life if you experienced angioedema with captopril 1, 2.
• The FDA drug label explicitly states captopril is contraindicated in patients hypersensitive to "any other angiotensin-converting enzyme inhibitor" 2.
• Angioedema occurs through bradykinin accumulation—a class effect shared by all ACE inhibitors including enalapril, lisinopril, and perindopril 1, 3.
• This reaction can occur at any time during treatment and may continue even after discontinuation 3.
• Never rechallenge with enalapril or any ACE inhibitor 1, 2.
• Consider angiotensin receptor blockers (ARBs) as alternatives, though use extreme caution as cross-reactivity occurs in <10% of cases 1, 3.

2. Cough (Most Common Side Effect)

• Cough affects 5-10% of white patients and up to 50% of Chinese patients 1.
• This is a class effect mediated by bradykinin accumulation—switching from captopril to enalapril will not help 1.
• If cough recurs after rechallenge with another ACE inhibitor, this confirms the class effect 1.
• ARBs are the appropriate alternative, as they do not cause cough 1.

3. Skin Rash, Taste Disturbance, or Proteinuria (Captopril-Specific)

• These reactions are captopril idiosyncrasies related to its sulfhydryl group, not shared by enalapril 4, 5.
• Research demonstrates lack of cross-reactivity: patients with captopril-induced rash, taste disturbance, or proteinuria tolerated enalapril without recurrence 4, 5.
• In one study, all 11 patients who developed captopril side effects (proteinuria, rash, taste disturbance) successfully switched to enalapril without recurrence 5.
• Patch testing confirmed captopril-specific allergy with tolerance to enalapril and lisinopril 4.
• Enalapril is safe to use in these cases 4, 5.

Clinical Decision Algorithm

Step 1: Identify the exact reaction type to captopril:

• Angioedema (facial/tongue/throat swelling, difficulty breathing) → Avoid all ACE inhibitors permanently 1, 2
• Persistent dry cough → Avoid all ACE inhibitors, use ARB instead 1
• Rash, taste changes, or proteinuria → Enalapril is safe to trial 4, 5

Step 2: If angioedema occurred:

• Document absolute contraindication to all ACE inhibitors in medical record 2
• Prescribe ARB (valsartan, candesartan, losartan) with close monitoring for first dose 1
• Warn patient that ARB cross-reactivity risk exists but is <10% 3

Step 3: If captopril-specific reaction (rash/taste/proteinuria):

• Start enalapril at low dose (2.5 mg twice daily) 1
• Monitor for recurrence of symptoms over first 2-4 weeks 5
• Titrate to target dose if tolerated 1

Critical Safety Considerations

• Black patients, women, smokers, and those over 65 years have increased risk of ACE inhibitor-induced angioedema 3.
• Angioedema can occur with late onset—even after months to years of therapy 6.
• Antihistamines and corticosteroids are ineffective for ACE inhibitor-induced angioedema 3.
• Monitor renal function and potassium within 1-2 weeks of starting any ACE inhibitor or ARB 1, 7.