Allopurinol Dosing for Gout
Starting Dose
Start allopurinol at 100 mg once daily in patients with normal renal function, or 50 mg once daily in patients with stage 4 or worse chronic kidney disease (CKD). 1, 2, 3, 4
- For patients with CKD stage 3, begin with 50-100 mg daily 1, 5
- The low starting dose minimizes the risk of allopurinol hypersensitivity syndrome (AHS) and acute gout flares 1, 4, 5
- Starting doses ≥1.5 mg per unit of estimated GFR (mg/ml/minute) are associated with a 23-fold increased risk of AHS 5
Dose Titration Schedule
Increase allopurinol by 100 mg increments every 2-4 weeks until serum uric acid reaches <6 mg/dL. 1, 2, 3, 4
- Check serum uric acid every 2-4 weeks during active dose titration 2, 6
- Continue titration until target is achieved, even if this requires doses above 300 mg daily 1, 2, 3
- More than 50% of patients require doses exceeding 300 mg daily to reach target serum uric acid 2, 3
- The maximum FDA-approved dose is 800 mg daily 3, 4
- Doses exceeding 300 mg should be administered in divided doses 2, 4
Target Serum Uric Acid Levels
The therapeutic target is serum uric acid <6 mg/dL for all gout patients. 1, 2, 3, 4
- For patients with severe gout (tophi, chronic arthropathy, or frequent attacks), target <5 mg/dL 1, 2, 6, 3
- Once target is achieved, monitor serum uric acid every 6 months 2, 3
Mandatory Flare Prophylaxis
Always initiate concomitant anti-inflammatory prophylaxis when starting or titrating allopurinol. 1, 6, 3
- Options include colchicine (0.5-1.2 mg daily), NSAIDs, or prednisone/prednisolone 1, 6
- Continue prophylaxis for 3-6 months after starting allopurinol, with ongoing evaluation 1, 6, 3
- Extend prophylaxis duration if flares persist during dose titration 1, 3
Dosing in Chronic Kidney Disease
Allopurinol remains the preferred first-line agent even in patients with CKD stage ≥3, but requires dose adjustment based on creatinine clearance. 1, 6, 3
CKD Stage 3 (CrCl 30-59 mL/min):
- Start at 50-100 mg daily 1, 2
- Titrate gradually with close monitoring for adverse events 1, 7
- Can safely increase above 300 mg with appropriate monitoring 2, 3, 7
CKD Stage 4 (CrCl 15-29 mL/min):
- Start at 50 mg daily 2, 3
- Maximum dose 200 mg daily per FDA labeling 4
- However, recent evidence supports careful titration above this with monitoring 2, 3, 7
CKD Stage 5 (CrCl <15 mL/min):
- Start at 50 mg daily 2
- Maximum dose 100 mg daily per FDA labeling 4
- Consider extending dosing intervals in extreme renal impairment (CrCl <3 mL/min) 4
Important: Patients with advanced CKD accumulate oxypurinol (active metabolite) and may achieve greater serum uric acid lowering at lower doses than those with normal renal function. 8
Special Considerations
HLA-B*5801 Testing:
- Consider testing prior to initiation in Korean patients with CKD stage ≥3, and in Han Chinese or Thai patients regardless of renal function 1, 3
Monitoring During Titration:
- Monitor for hypersensitivity reactions (rash, pruritus, elevated liver enzymes, eosinophilia) 3
- Mild elevations in liver function tests are common and generally not clinically significant 7
- Renal function does not deteriorate with dose escalation when monitored appropriately 7
Critical Pitfalls to Avoid
Do not rely on the standard 300 mg dose without titration to target—this fails to achieve therapeutic serum uric acid in more than half of patients. 2, 3
Do not use outdated renal dosing algorithms that cap allopurinol at 300 mg in CKD—doses can be safely increased with proper monitoring. 2, 3, 7
Do not discontinue allopurinol after achieving symptom control—87% of patients experience recurrence of gout flares within 5 years of discontinuation. 2, 6
Do not wait for a gout flare to resolve before starting allopurinol—initiation during a flare is acceptable with appropriate prophylaxis. 1, 6
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