Allopurinol × Captopril

The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). The mechanism is not fully established; presumed to be an immune reaction to metabolites of both drugs in chronic kidney disease.

Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing (Stevens-Johnson syndrome), angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.

Avoid the combination, especially in chronic kidney disease (higher risk). Alternative to ACE-I: an ARB (losartan) for antihypertensive needs. If rash or fever emerges, stop both drugs immediately.