Vázquez-Mellado J, Morales E M, Pacheco-Tena C, Burgos-Vargas R
Rheumatology Unit, Hospital General de México, México DF.
Ann Rheum Dis. 2001 Oct;60(10):981-3. doi: 10.1136/ard.60.10.981.
Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance. However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (< or =390 micromol/l) and to halt disease progression.
To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate.
Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed. Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol.
During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate. Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three of these (including the case of AHS) occurred in group A and two in group B (p=NS). The duration of allopurinol treatment was the same in both groups (group A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in group B had a creatinine clearance rate of <50 ml/min. None of the patients received concomitant diuretics, ampicillin, or azathioprine.
No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopurinol maintenance doses than those recommended according to creatinine clearance rate.
由于别嘌醇的严重不良反应与肌酐清除率降低和氧嘌呤醇半衰期延长有关,因此建议根据肌酐清除率调整剂量。然而,在一些痛风患者中,该剂量不足以降低血清尿酸水平(≤390微摩尔/升)并阻止疾病进展。
根据剂量和肌酐清除率确定原发性痛风患者中别嘌醇所致不良反应的发生率。
回顾性分析120例接受别嘌醇治疗的痛风患者的数据,这些患者起始剂量根据肌酐清除率进行调整,部分患者随后增加剂量以控制病情。比较两组:A组,52例接受根据肌酐清除率调整维持剂量别嘌醇的患者;B组,68例接受未调整的较高维持剂量别嘌醇的患者。
随访期间,57%的患者需要比根据其肌酐清除率推荐的剂量更高的别嘌醇剂量。120例连续患者中仅5例(4%)出现别嘌醇相关不良反应:4例轻微皮肤反应和1例别嘌醇超敏综合征(AHS)。其中3例(包括AHS病例)发生在A组,2例发生在B组(p=无显著性差异)。两组别嘌醇治疗持续时间相同(A组:2.3(3.3)年;B组:3.7(4.8)年)。A组无患者肌酐清除率<50毫升/分钟,而B组为44%。所有患者均未同时服用利尿剂、氨苄西林或硫唑嘌呤。
接受高于根据肌酐清除率推荐剂量的别嘌醇维持剂量的患者,别嘌醇不良反应发生率未见增加。