Major
Allopurinol × Enalapril
Xanthine oxidase inhibitors×Angiotensin-converting enzyme inhibitors (ACEi)
Mechanism
The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). Risk is higher in chronic kidney disease. Mechanism: presumed immune reaction to metabolites of both drugs.
Symptoms
Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing, angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.
Management
Avoid the combination, especially in chronic kidney disease. Alternative to ACE-I: an ARB (losartan, valsartan). If rash or fever emerges, stop both drugs immediately.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.