Allopurinol 4- Benzbromarone

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. 

The daily dose of benzbromarone is 50-200 mg. In combination with allopurinol, the benzbromarone dose is reduced to 20 mg. Benzbromarone is well tolerated. Rare side effects are headaches, gastrointestinal problems, and exanthems. 

Lartigue-Mattei, C., Chabard, J.L., Ristori, J.M., Bussiere, J.L., Bargnoux, H., Petit, J., and Berger, J.A., Kinetics of allopurinol and it s metabolite oxypurinol after oral administration of allopurinol alone or associated with benzbromarone in man. Simultaneous assay of hypoxanthine and xanthine by gas chromatogra-phy-mass spectrometry, Fund. Clin. Pharm., 5,621,1991. 

This potent uricosuric agent is used in Europe. It is a potent and reversible inhibitor of the urate-anion exchcmger in the proximal tubule. As the micronized powder, it is effective in a single daily dose of 40-80 mg. It is effective in patients with renal insufficiency and may be useful clinically in patients who are either allergic or refractory to other drugs used for the treatment of gout. Preparations that combine allopurinol and benzbromarone lower serum uric acid levels more effectively than either drug alone, despite the fact that benzbromarone lowers plasma levels of oxypurinol, the active metabolite of allopurinol. 

Pyrazinamide commonly causes hyperuricaemia and may therefore reduce the uricosuric effect of benzbromarone and probenecid. Allopurinol is unlikely to be effective against pyrazinamide-induced hyperuricaemia, and may exacerbate the situation, whereas benzbromarone may have modest efficacy in reducing hyperuricaemia caused by pyrazinamide. 

Twenty-five kidney transplant patients taking eielosporin were given benzbromarone 100 mg daily to treat hyperurieaemia. The plasma uric acid levels decreased from 579 to 313 micromol/L and the 24-hour urinary uric acid secretion rose from 2082 to 3233 micromol after 4 weeks of treatment. The plasma uric acid levels normalised in 21 of the patients who had creatinine clearances of over 25 mL/minute. No significant adverse effects developed and the ciclosporin serum levels remained unchanged. The authors of the report emphasise the advantages of benzbromarone over allop-urinol because of its efficacy, lack of significant adverse effects and because, unlike allopurinol, it does not interact with azathioprine, which often accompanies ciclosporin treatment. ... 

Probenecid appears to increase the renal excretion of the active metabolite of allopurinol, oxipurinol, while allopurinol is thought to inhibit the metabolism of probenecid. Allopurinol can increase the half-life and raise the serum levels of probenecid by about 50% and 20%, respectively. In another study, benzbromarone lowered the AUC of oxipurinol by about 40%, but did not affect allopurinol levels. ... 

Muller FO, Scl ll Groenewoud G, Hundt HKL, van der Merwe JC, van Dyk M The effect of benzbromarone on allopurinol/oj urinol kinetics in patients witii gout EurJ Clin Phar-maco/(1993) 44,69-72. 

Probenecid and benzbromarone increase the renal excretion of oxipurinol, the active metabolite of allopurinol, but this probably does not alter clinical efficacy. Theoretically, the use of uricosuric drugs with allopurinol could lead to uric acid precipitation in the kidneys and therefore maintenance of a high urine output is recommended when allopurinol is given by injection. Probenecid markedly increases the serum levels of allopurinol riboside, which may be advantageous in some circumstances. 

Like benziodarone (3) benzbromarone remains affective in case of mild renal failure in eight of our cases, blood creatinine level was over 2 mg per cent, and this, is of practical interest, in some of our patients with nephropathy who became intolerant either to allopurinol or to thiopurinol and developed cutaneous rashes. 

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