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Allopurinol, oxipurinol, benzbromarone and probenecid for lowering uric acid

 

Clinical bottom line

They work, in that serum uric acid levels are reduced, but evidence for reduced incidence of acute attacks is not extensive.


References


HE Paulus et al. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis and Rheumatism 1974 17: 609-614.


HR Arntz et al. Serum uric acid lowering effect of allopurinol and benzbromarone in low dosage. Fortschr Med 1979 19: 1-3.


GW Schepers et al. Benzbromarone therapy in hyperuricaemia: comparison with allopurinol and probenecid. J Int Med Res 1981 9: 511-515.


PW Bull & JT Scott. Intermittent control of hyperuricaemia in the treatment of gout. J Rheumatol 1989 16: 1246-1248.


H Berg. Effectiveness and tolerance of long-term uricosuric treatment. Z Gestamte Inn Med 1990 45: 719-20.


I Walter-Sack et al. Uric acid lowering effects of oxipurinol sodium in hyperuricaemic patients - therapeutic equivalence to allopurinol. J Rheumatol 1996 23: 498-501.

 

Background

Allopurinol, oxipurinol, benzbromarone and probenecid are treatments that lower uric acid, and which are used for treatment of gout. Reducing uric acid should reduce the number and severity of acute attacks, tophus formation, and disability. Bandolier is seeking the evidence base for this (June 2002), but the trials are often old and hard to find. Outcomes are neither always clear, nor useful. Reduction in serum uric acid is always reported, but studies are usually too small to report on adverse effects or on clinical outcomes like reduction in acute attacks.

While studies are being found, or until a systematic review appears, new information will be added to this page as it appears. Table 1 summarises the studies.

Table 1: Allopurinol, benzbromarone and probenecid in gout

Reference Design Included patients Outcomes Results
HE Paulus et al, 1974 Randomised, double blind comparison of probenecid 500 mg three times a day plus placebo versus probenecid plus colchicine for up to six months 53 men with gout and serum uric acid above 7.5 mg/dL Uric acid Results reported only for men with significant and sustained falls in uric acid (38/52), when mean reduction was to 6.3 mg/dL from about 8.8 mg/dL. Acute attacks 0.5/month with probenecid alone, and 0.2/month with probenecid plus colchicine. Pretreatment attacks averaged 3-4/12 months.
Arntz et al, 1979 Random comparison of 100 mg allopurinol, 20 mg benzbromarone and the combination in a crossover trial with four week treatment periods Twelve patients with hyperuricaemia and type IV hyperlipidaemia Uric acid Significant falls for all treatments, but more so for the combination.
Schepers, 1981 Non-random crossover of probenecid 1000 mg, allopurinol 300 mg daily, benzbromarone 100 mg daily in six patients. One week of treatment with two week wash out. Serum uric acid of 450 µmol/L or more. Uric acid Claims benzbromarone superior to other two treatments
Bull & Scott, 1989 Random (last digit of hospital number) to continuous daily allopurinol 300 mg (10) or allopurinol 300 mg (10) for two months every year. Aim of continuous treatment was uric acid below 6 mg/100 mL. Duration 2-4 years. At least three attacks of classical gouty arthritis with hyperuricaemia. Patients new to allopurinol. Acute attacks 20 attacks versus 26 attacks (continuous /intermittent) in first two years. No attacks per 166 patient months thereafter for continuous, versus 10/140 months for intermittent.
Berg, 1990 Randomised comparison of 100 mg allopurinol plus 20 mg benzbromarone daily compared with 300 mg allopurinol over 24 weeks. Serum uric acid above 6 mg/100 mL in 30 patients with asymptomatic hyperuricaemia. Uric acid In both groups mean uric acid fell from over 7 mg/100 mL to about 5.5 mg/100 mL.
Walter-Sack et al, 1996 randomised, double blind crossover study of rapid release allopurinol 300 mg/day and 384 mg/day of oxipurinol sodium for 14 days each. Plasma uric acid above 7.5 mg/100 mL in men Uric acid Mean pretreatment levels of about 8.5 mg/100 mL fell to about 5.5-6.0 mg/dL with treatment.

Comment

Not exactly a wealth of information yet. The longer duration study by Bull & Scott implies that maintaining a serum uric acid level below 6 mg/100 mL (350 µmol/L) eventually depletes body stores and gives good relief from acute attacks. The Paulus probenecid study did not appear to show any reduction in attacks without addition of prophylactic colchicine.