Can Febuxostat and Prednisone Be Given Together?
Yes, febuxostat and prednisone can and should be given together when initiating urate-lowering therapy for gout. 1
Strong Recommendation for Concurrent Use
The American College of Rheumatology strongly recommends administering concomitant anti-inflammatory prophylaxis therapy (including prednisone/prednisolone) when initiating febuxostat or any urate-lowering therapy. 1 This combination is not only safe but is considered standard of care to prevent gout flares during the initial months of treatment. 1
Evidence Supporting Combined Use
Prophylaxis reduces flare frequency and severity: Real-world clinical data demonstrates that patients receiving prophylactic steroids (mean dose 7.55 mg prednisone equivalent daily) during febuxostat initiation experienced significantly fewer total flares (0.96 vs 2.47 without prophylaxis, p=0.000) and less severe flares. 2
Duration of prophylaxis: Continue prednisone prophylaxis for 3-6 months minimum when starting febuxostat, with extension beyond 6 months if the patient continues to experience flares. 1 The optimal duration in clinical studies was approximately 6 months. 2
Dosing for prophylaxis: A prednisone dose of 7.5 mg daily (or equivalent) is effective and well-tolerated for flare prophylaxis during febuxostat initiation. 2
No Significant Drug Interactions
There are no clinically significant drug interactions between febuxostat and prednisone. 3 Febuxostat has very few known drug interactions, with the most important being azathioprine (and other drugs metabolized by xanthine oxidase). 1, 3 Corticosteroids like prednisone are not metabolized via pathways that interact with febuxostat's mechanism of action as a xanthine oxidase inhibitor. 3
Critical Distinction: Azathioprine Warning
While febuxostat and prednisone are safe together, never combine febuxostat with azathioprine - this carries a substantially increased risk of life-threatening myelotoxicity. 1 This warning applies to all xanthine oxidase inhibitors (both allopurinol and febuxostat theoretically have similar effects). 1
Practical Implementation
Start febuxostat at low dose: Begin with 40 mg daily or less, then titrate upward every 2-4 weeks to reach target serum urate <6 mg/dL. 1
Initiate prednisone simultaneously: Start prednisone 7.5 mg daily (or equivalent corticosteroid) on the same day as febuxostat. 2
Monitor for corticosteroid side effects: Watch for mood disorders, dysphoria, elevated blood glucose, immune suppression, and fluid retention - these are the known harms of corticosteroids, not drug interactions with febuxostat. 1
Alternative prophylaxis options: If prednisone is contraindicated, colchicine (0.5-1 mg daily) or NSAIDs are equally recommended alternatives for flare prophylaxis. 1 Colchicine may be slightly superior to steroids in reducing flare frequency. 2
Common Pitfalls to Avoid
Do not skip prophylaxis: Initiating febuxostat without anti-inflammatory prophylaxis leads to significantly more frequent and severe gout flares, which reduces patient adherence to urate-lowering therapy. 2
Do not stop prophylaxis too early: Discontinuing prednisone before 3 months increases flare risk during the critical period when urate crystals are mobilizing. 1
Do not confuse prophylactic dosing with treatment dosing: The 7.5 mg daily prednisone dose is for flare prevention; acute gout flares require higher therapeutic doses of corticosteroids. 1