From the Guidelines
Febuxostat and allopurinol should not be given together. These medications are both xanthine oxidase inhibitors that work through the same mechanism to lower uric acid levels, so combining them does not provide additional therapeutic benefit but increases the risk of side effects. Taking both medications simultaneously could lead to excessive uric acid lowering and potentially cause more adverse effects such as rash, liver function abnormalities, or hypersensitivity reactions. Instead, these medications should be used as alternatives to each other - allopurinol is typically tried first for gout management, while febuxostat may be used when allopurinol is not tolerated or is ineffective. If changing from one medication to the other, it's essential to discontinue the first medication before starting the second. The appropriate dosing depends on kidney function and treatment response, with allopurinol typically started at 100mg daily and febuxostat at 40mg daily, then titrated based on uric acid levels, as suggested by the American College of Physicians guideline 1. Patients should always consult their healthcare provider before making any changes to their gout medication regimen.
Some key points to consider:
- High-quality evidence from a systematic review showed no difference between febuxostat (40 mg/d) and allopurinol (300 mg/d) for decreasing serum urate levels 1.
- Evidence comparing harms between allopurinol and febuxostat was inconclusive, partly because of limited information about the adverse effects of febuxostat 1.
- Prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy, as supported by high-quality evidence from a randomized controlled trial (RCT) 1.
It is crucial to weigh the benefits and risks of urate-lowering therapy and discuss them with patients before initiating treatment, considering factors such as costs, individual preferences, and potential adverse effects, as recommended by the American College of Physicians guideline 1.
From the Research
Combination Therapy of Febuxostat and Allopurinol
- There is no direct evidence from the provided studies that febuxostat and allopurinol can be given together as a standard treatment regimen for hyperuricemia or gout.
- However, a study 2 mentions that lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of adverse events.
Efficacy and Safety Comparison
- Studies 3, 2, 4, and 5 compare the efficacy and safety of febuxostat and allopurinol, with febuxostat generally showing greater urate-lowering efficacy, especially in patients with renal impairment.
- Febuxostat is also shown to be well-tolerated, with similar or lower rates of adverse events compared to allopurinol 3, 2, 4, and 5.
Renal Outcomes
- A systematic review 6 suggests that febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and chronic kidney disease, based on evidence from small long-term retrospective studies with serious risk of bias.
- However, more methodologically rigorous studies are needed to determine the clinical applicability of these results 6.