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

Introduction: Allopurinol is still the drug of choice for the long-term 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 micromol/L).

Methods: Prospective trial was carried out in patients with primary gout and normal renal function, no relevant liver disease, and SUc-lowering treatment indications involving 1-2 gout episodes per year, presence oftophus and/or chronic urate arthropathy or X-ray finding of erosions. The patients were administered allopurinol in a step-up 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: Forty-one patients were enrolled in the study; 27 ended 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 micromol/L to 346.9+/-87.9 micromol/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 micromol/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.