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Table 1. Gout patients that may be candidates for benzbromarone or allopurinol for 3 months resulted in
uricase-polyethylene glycol 20 a statistically significant, but modest, drop in uric acid
(285.5 mol/L to 261.7 mol/L for benzbromarone, and
Organ transplant patients with recurrent gout attacks 356.9 mol/L to 327.1 mol/L for allopurinol). This approxi-
or tophi
mately 15% lowering of uric acid with fenofibrate and
Allopurinol allergy patients
Renal insufficiency patients benzbromarone or allopurinol was less than that observed
Tumor lysis hyperuricemia patients in a prior study with fenofibrate and allopurinol [52],
Acute gout attacks not responding to conventional but similar to that observed in a prior study of fenofibrate
treatments (200 mg per day) and losartan in non-diabetes patients
Chronic gout patients not responding to conventional with hypertension treated for 8 weeks [53].
treatments Another study used fenofibrate (200 mg per day) in
patients with gout on allopurinol (300 to 900 mg per day)
[54]. Fenofibrate was associated with a 19% reduction in
pyrimidine metabolism [48]. This drug is a more potent serum urate after 3 weeks of treatment. Long-term treat-
inhibitor of xanthine oxidase in vitro and in animals than ment of two patients with fenofibrate resulted in sustained
allopurinol. The pharmacokinetics and pharmacodynam- reduction in lipid levels, with remission from recurrent
ics of febuxostat 80 mg orally once per day for 7 days have attacks of gout [55]. There is a similar case reporting the
been evaluated in male and female subjects with normal usefulness of fenofibrate [56].
and abnormal renal function [49]. No serious adverse Fenofibrate (200 mg per day) also was investigated in an
events were reported, although diarrhea, abdominal pain, 8-week trial in patients without diabetes with hypertension
and headache occurred. There was no clinically significant treated with indapamide, which is associated with hyper-
change in the pharmacodynamics with increasing renal uricemia [57]. Indapamide induced hyperuricemia, because
impairment. Based on this study, dose adjustment for renal of a decrease in the fractional excretion of uric acid, and was
dysfunction does not appear necessary. An 8-week dose- reversed in a statistically significant manner with feno-
response (10, 20, or 40 mg daily) clinical trial in Japanese fibrate, because of an in-urate excretion. Thus, fenofibrate
subjects with gout or hyperuricemia has been reported may correct the hyperuricemia induced by indapamide.
[50]. Febuxostat reduced serum uric acid levels in a dose- This modest effect of fenofibrate and losartan nonethe-
dependent manner and was equally effective in under- less may be useful for patients with hypertension and
excretors and over-producers. The most frequent side hyperlipidemia associated with gout; their role in asympto-
effects were gout flare, common cold syndrome, and ele- matic hyperuricemia remains to be elucidated [58]. Losar-
vated C-reactive protein, creatine kinase, and serum tan is not without side effects; a case of exercise-induced
glutamate pyruvate transaminase; three of 96 (3%) febux- acute renal failure with hypouricemia, and acute tubular
ostat-treated subjects prematurely terminated the treat- necrosis with interstitial necrosis has been reported [59].
ment because of adverse events. The role of long-term fenofibrate therapy on hyperurice-
Febuxostat and Y-700 are promising oral xanthine oxi- mia and attacks of gout in patients with hyperlipidemia
dase inhibitors. Further studies in larger patient groups are is not yet determined. The fenofibrate decrease in serum
needed to confirm their effectiveness and safety. Combina- uric acid is modest (approximately 15% to 20%) and has
tion therapy with allopurinol also should be investigated. only been evaluated in short-term studies. Longer-term
studies are needed to attempt to confirm its usefulness as
chronic therapy in patients with hyperuricemia.
Fenofibrate, Losartan, and Amlodipine Amlodipine, a calcium channel blocker, also has been
Fenofibrate, a hypolipidemic fibric acid derivative, and investigated in cyclosporin-induced hyperuricemia in
losartan, an angiotensin II receptor antagonist, have been hypertensive renal transplant recipients [60]. Patients on
reported to reduce serum uric acid through enhanced renal a stable dose of cyclosporin were randomized to receive
clearance. These agents were studied in combination with amlodipine (5 to 10 mg per day) or the beta-adrenorecep-
the antihyperuricemic agents benzbromarone (50 mg once tor antagonist tertatolol (5 to 10 mg per day) for 60 days.
daily) or allopurinol (200 mg twice a day) [51]. Benzbro- Amlodipine statistically significantly decreased serum
marone was used for underexcretory gout and allopurinol uric acid, although the effect was modest (483 mol/L to
for overexcretors of uric acid. The addition of fenofibrate 431 mol/L). Tertatolol significantly increased serum uric
(300 mg once daily) to hypertriglyceridemic patients with acid. Amlodipine may be useful in treatment of hyper-
gout taking benzbromarone or allopurinol resulted in a tension in hypertensive, hyperuricemic renal transplant
statistically significant drop in serum uric acid at 2 months, patients. Benziodarone and allopurinol have been shown
although the effects were modest (350.9 mol/L to 297.4 to be effective in controlling hyperuricemia in renal trans-
mol/L for benzbromarone, and 362.8 mol/L to 309.3 mol/ plant patients, and benziodarone at greater than 75 mg
L for allopurinol). Similarly, addition of losartan (50 mg per day is statistically significantly more effective than
once daily) to hypertensive patients with gout receiving allopurinol [61].
244 Crystal Arthritis
also may be beneficial. New treatments for hyperuricemia References and Recommended Reading
and its rheumatologic, vascular, and nephrologic sequelae Papers of particular interest, published recently, have been
are needed. highlighted as:
• Of importance
•• Of major importance
Acknowledgments 1. Arrondee E, Michet CJ, Crowson CS, et al.: Epidemiology
Grant support provided by US Food and Drug Administra- of gout: is the incidence rising? J Rheumatol 2002,
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246 Crystal Arthritis
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