From the Guidelines
Allopurinol should be switched to febuxostat in patients with hyperuricemia when they experience inadequate response to allopurinol, develop intolerance or adverse reactions to allopurinol, or have moderate to severe kidney impairment. According to the 2020 American College of Rheumatology guideline for the management of gout 1, the decision to switch from allopurinol to febuxostat should be based on the individual patient's response to treatment and their underlying health conditions. Some key considerations for switching to febuxostat include:
- Inadequate response to allopurinol, defined as failure to reach target serum uric acid levels below 6 mg/dL despite appropriate dosing
- Intolerance or adverse reactions to allopurinol, such as rash, gastrointestinal upset, or liver function abnormalities
- Moderate to severe kidney impairment, defined as a creatinine clearance (CrCl) of less than 60 mL/min, where allopurinol dosing becomes challenging When transitioning from allopurinol to febuxostat, the following steps can be taken:
- Febuxostat is typically started at a dose of 40 mg daily and can be increased to 80 mg daily if needed to reach target uric acid levels
- No washout period is required between medications, but patients should be monitored for potential gout flares during the transition
- Febuxostat works by selectively inhibiting xanthine oxidase and is metabolized primarily by the liver, making it suitable for patients with renal impairment However, febuxostat should be used with caution in patients with cardiovascular disease, as some studies have suggested a potential increased risk of cardiovascular events compared to allopurinol 1. It's also important to note that the 2017 updated EULAR evidence-based recommendations for the management of gout suggest that febuxostat or a uricosuric are indicated if allopurinol cannot be tolerated or if the SUA target cannot be reached by an appropriate dose of allopurinol 1. Overall, the decision to switch from allopurinol to febuxostat should be individualized and based on the patient's specific needs and health status.
From the Research
Switching from Allopurinol to Febuxostat
- Allopurinol is commonly used to treat hyperuricemia, but it may not be suitable for patients with renal impairment due to the risk of allopurinol hypersensitivity syndrome (AHS) 2.
- Febuxostat is a non-purine, selective xanthine oxidase inhibitor that does not require dosage adjustment in patients with mild or moderate renal impairment, making it a potential alternative to allopurinol 3.
- Studies have shown that febuxostat is more effective in lowering serum uric acid levels than allopurinol in patients with hyperuricemia and gout, particularly in those with renal impairment 3, 4, 5.
Indications for Switching
- Patients with chronic kidney disease (CKD) and hyperuricemia may benefit from switching to febuxostat, as it has been shown to reduce serum uric acid levels and slow the progression of renal disease 4, 6.
- Renal transplant recipients with hyperuricemia may also benefit from switching to febuxostat, as it has been shown to reduce serum uric acid levels and improve renal function 5.
- Patients with gout and renal impairment who are at risk of AHS or have experienced adverse events with allopurinol may also be considered for switching to febuxostat 3, 2.
Considerations
- The decision to switch from allopurinol to febuxostat should be based on individual patient factors, including renal function, serum uric acid levels, and medical history 3, 4, 2, 5, 6.
- Close monitoring of serum uric acid levels and renal function is recommended after switching to febuxostat to ensure efficacy and safety 4, 5.