From the Guidelines
Allopurinol is typically the preferred initial choice for treating gout and hyperuricemia due to its lower cost, extensive safety record, and once-daily dosing, while febuxostat may be more suitable for patients with renal impairment or those who have failed allopurinol therapy. The choice between allopurinol and febuxostat depends on various factors, including patient characteristics, comorbidities, and potential side effects. Key differences between the two medications include:
- Dosing: Allopurinol is typically started at 100mg daily and titrated up to 300-600mg daily as needed, while febuxostat is usually dosed at 40-80mg daily.
- Mechanism of action: Both medications inhibit xanthine oxidase to reduce uric acid production, but febuxostat is more selective in its inhibition.
- Side effects: Allopurinol can cause rash, while febuxostat carries a higher cardiovascular risk and cost.
- Monitoring: Regular monitoring of liver function, renal function, and uric acid levels is necessary for both medications, with a target serum uric acid level below 6 mg/dL for most patients. According to the most recent and highest quality study 1, febuxostat (80 mg/d) was more effective than allopurinol (300 mg/d) at decreasing serum urate levels, but there was no difference in gout flare incidence between lower doses of febuxostat (40 or 80 mg/d) and allopurinol (100 to 300 mg/d). Some important considerations when initiating either medication include:
- Counseling patients about potential gout flares during the first few months of therapy, which can be mitigated with prophylactic colchicine, NSAIDs, or low-dose corticosteroids.
- Adjusting doses according to renal function and monitoring for adverse effects.
- Considering alternative therapies, such as uricosurics or combination therapy, for patients who do not respond to or cannot tolerate allopurinol or febuxostat.
From the Research
Comparison of Allopurinol and Febuxostat
- Allopurinol and febuxostat are two commonly used medications for the treatment of hyperuricemia, with allopurinol being the first-line drug for serum urate-lowering therapy in gout 2.
- Febuxostat is clinically equivalent to allopurinol in terms of efficacy, but may have a more favorable safety profile in certain patients 3.
- A pooled analysis of registrative studies found that febuxostat was more effective than allopurinol in lowering serum uric acid levels in patients with gout and hyperuricemia, with a higher proportion of patients achieving target serum uric acid levels (<6 mg/dL or ≤5 mg/dL) 4.
Efficacy and Safety
- Febuxostat has been shown to be more effective than allopurinol in achieving target serum uric acid levels, with a faster time to reach these levels 4.
- Allopurinol dosing is often limited to <300 mg/d due to concerns about hypersensitivity reactions, but this may not be sufficient to adequately control hyperuricemia in some patients 2.
- Febuxostat may be a suitable alternative for patients with financial limitations or those who do not respond to allopurinol, and can be used in combination with other medications such as probenecid to achieve synergistic effects 5.
Renal Outcomes
- A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and chronic kidney disease, with a higher estimated glomerular filtration rate and reduced risk for renal disease progression 6.
- However, the evidence is based on small long-term retrospective studies with serious risk of bias, and more methodologically rigorous studies are needed to determine the clinical applicability of these results 6.