Evaluation of the clinical dose and effectiveness of allopurinol and benzbromarone on hyperuricemia in patients with different renal function

• Main Authors: Pei-Fen Chuang, 莊佩芬
• Other Authors: Yaw-Bin Huang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/78434176373964277614

碩士 === 高雄醫學大學 === 臨床藥學研究所 === 96 === Background: There are some noticeable points for urate-lowering therapy. 1. The potential of allopurinol severe cutaneous adverse reactions led to the development of clinical guidelines that advocate dosing of allopurinol according to renal function. For achieving therapy target, appropriate dose adjustments of allopurinol should base on serum uric acid level. 2. Benzbromarone may have no effects on patients with severe renal dysfunction and treatment with this drug might lead to potential liver toxicity. 3. Poor compliance with urate-lowering therapy and a fixed dose of allopurinol may result in undertreatment and difficult management of disease. Objective: Dose for prescription, espically the adjusted dose in different renal function and the percent of regular laboratory monitoring are all prescription patterns discussed. The effectiveness of fixed daily dose after 3 months treatment and factors associated with 1 year compliance are all evaluated and analyzed in this study. Patients and methods: This study population is from a regional hospital in Kaohsiung who received allopurinol or benzbromarone prescriptions in 2004. Patients who were less than 18 years, with only one time prescription of urate-lowering drug and with prescriptions from dialysis department are excluded. Prescriptions from emergency department and inpatients are also exclusion criteria to enhance the doses for patients with stable situation. The prescription doses from 2004~2007/6 are analyzed. Newly treated patients with baseline serum uric acid and creatinine, with first 6 months of continued use and with gout are inclusion criteria for three different discussion parts including the daily dose in different renal function, the percent of regular laboratory monitoring and the association between factors and compliance. Results: The most commonly used allopurinol daily dose was 100 mg/day in these prescriptions of study population within 2004 to June 2007. Most patients received allopurinol 100 mg/day as initial daily dose, although with different renal function. More than 50% patients with lower allopurinol daily dose when compared with recommended. Patients receiving daily dose less than 100 mg/day were with more severe renal dysfunction. There were 11 patients receiving benzbromarone with renal function < 30 ml/min/1.73m2. Titrating allopurinol dose might not be considered in 60.0% patients with first 6 months of continued use and the awareness of the liver toxicity of benzbromarone might be less than 50%. In this study, the percent of patient achieving normal uric acid were 18.2% and 92.3% in patients with fixed allopurinol and benzbromarone daily dose 100 mg/day after 3 months treatment. Mean duration of continuous drug treatment was less than 3 months in newly treated patients and compliance with treatment for 1 year was 7.6% in gout patients. Increasing age was associated with compliance (odds ratio, 1.04; 95% confidence interval, 1.01-1.07, P-value=0.0091) and patients with more gout attacks within 1 year before the start of drug treatment was associated with compliance (odds ratio, 1.24; 95% confidence interval, 1.08-1.41, P-value=0.0018). Conclusions: Generally, the initial daily doses were lower than recommended, suggesting conservative therapy for fear of allopurinol severe cutaneous adverse reactions. Adjusting daily dose and monitoring uric acid adequately might bring more benefit of therapy because of few patients with fixed allopurinol 100 mg/day achieved normal uric acid after 3 months treatment. Benzbromarone 100 mg/day may well achieve target uric acid. It is noticeable that the awareness of possible liver toxicity in patients with benzbromarone might be less than 50%. Urate-lowering drugs were not being used long term in this study population. Age and the experience of gout attack before start of drug treatment were associated with compliance.