What is the typical starting dose of Allopurinol (xanthine oxidase inhibitor) for an adult patient with gout and normal renal function?

Allopurinol Dosing for Gout

Starting Dose

For adults with gout and normal renal function, start allopurinol at 100 mg once daily and titrate upward by 100 mg increments every 2-5 weeks until achieving a target serum uric acid level of <6 mg/dL, with most patients ultimately requiring 400-600 mg daily. 1

Initial Dosing by Renal Function

• Normal renal function (CrCl >60 mL/min): Start at 100 mg daily 2, 3, 1
• Stage 4 CKD or worse (CrCl <30 mL/min): Start at 50 mg daily 2, 3
• CrCl 10-20 mL/min: Maximum 200 mg daily 1
• CrCl <10 mL/min: Maximum 100 mg daily 1

The FDA label explicitly recommends starting with a low dose of 100 mg daily to reduce the risk of acute gout flares and hypersensitivity reactions 1. The 2012 American College of Rheumatology guidelines strongly support this approach, noting that the highest risk of severe allopurinol hypersensitivity syndrome occurs in the first few months of therapy 2. Research confirms that starting doses above 1.5 mg per unit of estimated GFR significantly increase hypersensitivity risk (odds ratio 23.2) 4.

Dose Titration Strategy

• Increase by 100 mg increments every 2-5 weeks based on serum uric acid monitoring 2, 3, 5
• Target serum uric acid: <6 mg/dL for all gout patients 3, 5, 1
• Lower target of <5 mg/dL for severe gout with tophi, chronic arthropathy, or frequent attacks 3, 5
• Maximum FDA-approved dose: 800 mg daily 3, 1

Dosing Above 300 mg Daily

More than 50% of patients fail to achieve target serum uric acid with allopurinol 300 mg daily or less, making dose escalation essential for most patients. 2, 3, 5 The American College of Rheumatology explicitly states that allopurinol can be safely titrated above 300 mg daily, even in patients with renal impairment, provided there is adequate monitoring for hypersensitivity reactions 2, 3.

• Doses exceeding 300 mg should be administered in divided doses 1
• The average maintenance dose is 400-600 mg daily for moderately severe tophaceous gout 1
• Outdated renal dosing algorithms that cap allopurinol at 300 mg in renal impairment should not be used 5

Mandatory Flare Prophylaxis

Concomitant anti-inflammatory prophylaxis must be initiated when starting allopurinol to prevent paradoxical gout flares. 3, 6, 1

Prophylaxis Options:

• Colchicine 0.5-1 mg daily (preferred) 3, 6
• Low-dose NSAIDs 3, 6
• Prednisone/prednisolone 3, 6

Continue prophylaxis for at least 3-6 months after starting allopurinol, with ongoing evaluation and extended prophylaxis if flares persist 3, 6. The FDA label emphasizes that maintenance doses of colchicine should generally be given prophylactically when allopurinol is begun 1.

Monitoring Requirements

During Titration Phase:

• Check serum uric acid every 2-5 weeks while actively titrating the dose 3, 6, 5
• Monitor for hypersensitivity reactions: pruritus, rash, elevated liver enzymes, eosinophilia 2, 3

After Achieving Target:

• Check serum uric acid every 6 months once target is achieved 3, 5

Special Considerations

HLA-B*5801 Screening

Consider HLA-B*5801 testing before initiating allopurinol in high-risk populations: 2, 3

• Korean patients with stage 3 or worse CKD (HLA-B*5801 allele frequency ~12%)
• Han Chinese or Thai patients regardless of renal function (HLA-B*5801 allele frequency ~6-8%)

If HLA-B*5801 positive, prescribe an alternative to allopurinol 2. Universal screening is not recommended for Caucasians (prevalence ~2%) 2.

Renal Impairment

Allopurinol remains the preferred first-line agent even in moderate-to-severe CKD (stage ≥3). 3, 6 Research demonstrates that patients with advanced CKD accumulate the active metabolite oxypurinol, potentially achieving greater serum urate lowering at lower doses 7. However, this may also create a ceiling effect, making careful dose titration essential 7.

Common Pitfalls to Avoid

• Do not rely solely on the standard 300 mg dose – this fails to achieve target urate levels in more than half of patients 2, 3, 5
• Do not discontinue allopurinol after achieving symptom control – approximately 87% of patients experience recurrence of gout flares within 5 years of discontinuation 6, 5
• Do not use outdated renal dosing algorithms that unnecessarily cap doses at 300 mg in renal impairment 2, 5
• Do not skip flare prophylaxis – inadequate prophylaxis during dose adjustment leads to increased flare frequency 3
• Ensure adequate hydration – maintain daily urinary output of at least 2 liters with neutral or slightly alkaline urine 1