The efficacy and tolerability of allopurinol dose escalation in patients with gout

Introduction. Allopurinol is still the drug of choice for the longterm control of hyperuricemia in patients with gout. Objective. The aim of the study was to investigate the efficacy and tolerability of different allopurinol doses used in order to attain a target serum uric acid concentration (SUc) of <6 mg/dl (360 µmol/L). Methods. Prospective trial was carried out in patients with primary gout and normal renal function, no relevant liver disease, and SUc­lowering treatment indications involving 1­2 gout episodes per year, presence of tophus and/or chronic urate arthropathy or X­ray finding of erosions. The patients were administered allopurinol in a step­up dose scheme (beginning with 100 mg/ day then raised for 100 mg every four weeks) until therapeutic goal was achieved or development of adverse effects. Results. Forty­one patients were enrolled in the study; 27 end­ ed it so far. The treatment target was reached in 19/27 patients using allopurinol 300 mg/day (70.4%). After the increased dose up to 600 mg/day, the overall treatment success was reached in 25/27 patients (92.5%). Adverse drug reactions (ADRs) were evidenced in 12/27 patients; the most frequent ADRs were gouty flares. The mean SUc reduction from baseline 533.9±83.4 µmol/L to 346.9±87.9 µmol/L was obtained with allopurinol at a dose of 300 mg/day (p=0.000) as well as at a dose up to 600 mg/day (274.9±92.7 µmol/L) (p=0.000). Conclusions. Most of the investigated gouty patients attained target SUc <360 mmol/L at a 300 mg/day allopurinol dose. However, in 30% of patients further dose escalation up to 600 mg/day was needed but the increased dose was well tolerated, and the therapeutic goal was achieved even in 92.5% of patients. Such doses are in general well tolerated under the conditions of well preserved renal function.

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