As First-Line Gout Tx, Allopurinol Is Effective, Economical

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“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.

“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,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “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,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “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 allopurnol. “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).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“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.

“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,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “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,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “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 allopurnol. “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).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“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.

“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,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “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,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “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 allopurnol. “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).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.