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.