SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite some competition from a newer drug, febuxostat, according to Dr. John Pendleton.
Allopurinol is generally very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the annual meeting of the American College of Physicians.
Photo credit: ©craftvision/iStockphoto.com
Photo credit:©craftvision/iStockphoto.comResearchers found that allopurinol was safe, effective and the most cost-effective as a first-line treatment for gout, compared with febuxostat.
"I still recommend allopurinol as the initial treatment, because you don’t need a 24-hour urine collection to give it; it’s effective in both overproducers and underexcretors [of uric acid]; it can be taken just once a day; and it’s safe and effective for those with mild renal insufficiency when the dose is adjusted," said Dr. Pendleton, an internist in Roanoke, Va.
Price is also an important factor, he noted. "Generic allopurinol costs about $15 per month. The brand name costs about $43 per month. But the price for febuxostat comes in at about $156 per month."
With either drug, the treatment goal should be to lower uric acid levels to be 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks. "This study noted that among the 81 patients with a uric acid of less than 6 mg/dL, 88% had no recurrent attacks during the 3-year observational period" (Arthritis Rheum. 2004;51:321-5).
Allopurinol has been the "standby drug" for gouty arthritis for 60 years, and still performs admirably, Dr. Pendleton said. Although most initial doses range from 50 to 300 mg/day, "some recent studies suggest that only 25% of patients will reach the uric acid target on that regimen. For many patients, we need to increase the dose to get that level down."
The dose should be incrementally increased every 3-4 weeks to reach the uric acid target level; doses of up to 800 mg/day are approved for this indication. "But if you’re not able to achieve this desired level by pushing the dose close to 800 mg, I would consider trying febuxostat."
Febuxostat, a xanthine oxidase inhibitor, is more selective and potent than allopurinol. "It’s metabolized in the liver and very little of the active drug is excreted renally, raising the possibility that it might be safer in patients with mild to moderate renal insufficiency," Dr. Pendleton said.
It’s not easy to fully compare the two, because all three of the studies on the basis of which febuxostat was approved used a fixed-dose allopurinol regimen. "None of them allowed the total upward titration of allopurinol for a fair comparison," Dr. Pendleton pointed out.
The studies concluded that 40 mg of febuxostat was as effective as 300 mg of allopurinol. "The higher dose [of febuxostat 80 mg] seemed to be more effective than 400 mg allopurinol, but again, the studies did not allow for an upward titration" of the comparator, he said.
Although none of the patients in those trials had a creatinine level of more than 2.5 mg/dL, "a short-term study suggests that febuxostat dosing would not need to be adjusted even with a very low creatinine clearance [of 10-29 mL/min]. But just the same I would be very careful in that setting," Dr. Pendleton said (Am. J. Ther. 2005;12:22-34).
Febuxostat also appears to be safe for patients with mild hepatic dysfunction, with an adverse event profile similar to that of allopurinol. However, febuxostat is contraindicated in patients who are taking azathioprine, mercaptopurine, and theophylline.
Probenecid could be another option for some patients, especially those who underexcrete uric acid. Although probenecid has a somewhat better adverse event profile than allopurinol, it requires a 24-hour urine collection to rule out overproduction of uric acid and it seems to increase the risk of kidney stones. The drug is not as effective in patients with a low creatinine clearance (less than 60 mL/min), and "seems to have no effect at all at a creatinine level of 30 mL/min or lower," Dr. Pendleton said. Probenecid also must be taken three times a day – another drawback, in his opinion.
Dr. Pendleton said that he had no relevant financial disclosures.