Allopurinol × Hydrochlorothiazide

Thiazide diuretics raise allopurinol and oxypurinol metabolite levels, increasing hypersensitivity risk, including allopurinol hypersensitivity syndrome (DRESS).

Rash, fever, facial oedema, lymphadenopathy, abnormal liver function. Reactions develop 2–8 weeks after starting allopurinol, more often in older patients and chronic kidney disease.

On the combination, dose allopurinol by creatinine clearance: if below 60 mL/min, start at 100 mg/day with titration of 100 mg every 4 weeks until target uric acid is reached. In Asian patients (especially Han Chinese and Thai), HLA-B*58:01 testing is recommended before starting allopurinol. Alternatives in hyperuricaemia: febuxostat (if no heart failure), or replace the thiazide with losartan (urocosuric effect).