No, Allopurinol and Febuxostat Should Not Be Given Together
Allopurinol and febuxostat must never be combined, as both are xanthine oxidase inhibitors with redundant mechanisms of action, and the 2012 American College of Rheumatology guidelines explicitly state that febuxostat and allopurinol should not be used in combination with each other. 1
Why Combination Therapy Is Contraindicated
- Both medications inhibit the same enzyme (xanthine oxidase) through different mechanisms, making concurrent use pharmacologically redundant 2
- Combining two xanthine oxidase inhibitors exposes patients to the adverse effect profiles of both medications simultaneously without any therapeutic justification 2
- The drug label information specifically prohibits their combined use 1
Appropriate Management Strategy for Your Patient
Given your patient's clinical scenario (type 2 diabetes, eGFR ≥45 mL/min/1.73 m², currently on prednisone for acute gout flare), you should:
Choose One Xanthine Oxidase Inhibitor and Titrate to Target
- Select allopurinol as first-line therapy for most patients with eGFR ≥60 mL/min, as it has over 40 years of clinical safety data 2
- Start allopurinol at ≤100 mg/day (lower if CKD present) and titrate upward every 2-5 weeks until serum uric acid <6 mg/dL is achieved 3, 2
- Maximum allopurinol dose can reach 800 mg daily when properly titrated 4
Alternative: Febuxostat Can Be Used Instead (Not In Addition)
- Febuxostat is preferred over allopurinol in patients with moderate-to-severe renal impairment (eGFR 30-59 mL/min) since it requires no dose adjustment for kidney function 2, 5
- Start febuxostat at ≤40 mg/day and titrate to 80 mg daily (maximum FDA-approved dose in the US) if serum uric acid remains >6 mg/dL after 2-4 weeks 3, 2
- Critical cardiovascular warning: If your patient has established cardiovascular disease, consider allopurinol instead of febuxostat due to increased CVD-related mortality risk with febuxostat 3, 2
If Single-Agent Therapy Fails to Achieve Target
When one xanthine oxidase inhibitor at maximum appropriate dose fails to achieve serum uric acid <6 mg/dL:
- Add a uricosuric agent (probenecid, fenofibrate, or losartan) to the xanthine oxidase inhibitor rather than combining two xanthine oxidase inhibitors 1
- The 2017 EULAR guidelines specifically recommend combining an xanthine oxidase inhibitor with a uricosuric for refractory cases 1
- Alternatively, switch from one xanthine oxidase inhibitor to the other (allopurinol to febuxostat or vice versa) in cases of drug intolerance or adverse events 1
Essential Prophylaxis Requirements
- Mandatory anti-inflammatory prophylaxis must be initiated when starting either medication: colchicine 0.5-1 mg daily, NSAIDs, or prednisone/prednisolone 3, 2
- Continue prophylaxis for 3-6 months, with ongoing evaluation if flares persist 3
- Since your patient is already on prednisone for the acute flare, you can initiate urate-lowering therapy immediately during the flare rather than waiting for resolution 3
Common Pitfalls to Avoid
- Never use both xanthine oxidase inhibitors simultaneously—this is the most critical error 1, 2
- Do not use the 40 mg febuxostat dose as the final dose without checking serum uric acid; most patients require 80 mg to achieve target 2
- Avoid switching between medications without ensuring adequate dose titration of the first agent 2
- Always provide flare prophylaxis throughout dose titration to prevent acute gout flares that commonly occur when initiating urate-lowering therapy 3, 2