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An initial allopurinol dose of 1.5 mg per unit of glomerular filtration rate seems reasonable.

參考機轉：圖解藥理學～11痛風發炎4

Acute hypersensitivity reactions — often including rash, hepatotoxicity, and renal toxicity — are a rare but feared complication of allopurinol. To determine whether the starting dose of allopurinol is a risk factor for hypersensitivity, New Zealand researchers identified 54 cases of allopurinol hypersensitivity syndrome that occurred during a 12-year period in patients with gout. Each case patient was matched (by age, sex, diuretic use, and renal function) with three allopurinol-treated controls with gout who did not develop hypersensitivity. At baseline, estimated mean glomerular filtration rate (GFR) was about 50 mL/minute/1.73 m² in both cases and controls.

Median time from starting allopurinol to development of acute hypersensitivity was 30 days; nearly all reactions developed within 6 months. The starting dose was significantly higher in cases than in controls (mean, 184 vs. 112 mg daily). Among cases, mean daily dose was 218 mg at the time of the reaction. Eventually, however, many controls received daily allopurinol doses >200 mg. From these data, the authors estimate that a starting dose of roughly 1.5 mg of allopurinol per unit of estimated GFR (e.g., 100 mg daily for a person with a GFR of 70 mL/minute/1.73 m²) would lower risk for hypersensitivity.

Comment: Despite the limitations of case-control methodology in establishing cause and effect, the authors' recommended formula for determining an allopurinol starting dose is reasonable. They also recommend that clinicians increase doses slowly (i.e., over many months), because rushing to lower uric acid is unnecessary as long as patients are "covered" by low-dose colchicine or nonsteroidal anti-inflammatory drugs to prevent breakthrough gout attacks.

— Allan S. Brett, MD

Published in Journal Watch General Medicine August 21, 2012