What is the recommended dosage of allopurinol (xanthine oxidase inhibitor) for gout prevention?

Allopurinol for Gout Prevention: Dosing Strategy

Starting Dose

Start allopurinol at 100 mg once daily for all patients with normal renal function, and 50 mg daily for patients with stage 4 or worse chronic kidney disease. 1

• The low starting dose minimizes the risk of allopurinol hypersensitivity syndrome (AHS), which increases dramatically with higher initial doses 2
• Starting doses ≥1.5 mg per unit of estimated GFR are associated with a 23-fold increased risk of AHS 2
• The FDA label recommends starting at 100 mg daily to reduce the possibility of acute gout flare-ups 3

Dose Titration Protocol

Increase the dose by 100 mg every 2-4 weeks until serum uric acid is <6 mg/dL, without exceeding 800 mg daily. 4, 1

• Monitor serum uric acid every 2-5 weeks during titration 1
• The American College of Rheumatology emphasizes that doses up to 300 mg can be given as a single daily dose, but doses exceeding 300 mg should be divided 1, 3
• Most patients require doses above 300 mg daily to achieve target uric acid levels 1
• More than 50% of patients fail to achieve target with 300 mg daily or less 1

Therapeutic Target

The primary goal is to maintain serum uric acid <6 mg/dL (360 μmol/L) for all gout patients. 4, 1

• For patients with severe gout (tophi, chronic arthropathy, frequent attacks), target <5 mg/dL until complete crystal dissolution occurs 4, 1
• Once crystal dissolution is achieved in severe gout, the target can be relaxed back to <6 mg/dL 5

Prophylaxis During Initiation

Concomitant anti-inflammatory prophylaxis with colchicine or NSAIDs is strongly recommended during the first 3-6 months of allopurinol therapy. 4, 3

• Acute gout flares commonly occur during early allopurinol therapy due to mobilization of urate crystals from tissue deposits 3
• Continue prophylaxis until serum uric acid has normalized and the patient has been free from acute attacks for several months 3
• Initiating allopurinol during an acute gout attack does not prolong the attack when appropriate anti-inflammatory therapy is used 6

Dose Escalation in Renal Impairment

Allopurinol can be safely titrated above 300 mg even in patients with moderate to severe chronic kidney disease, with appropriate monitoring. 1

• The American College of Rheumatology recommends allopurinol as the preferred first-line agent for all patients with gout, including those with moderate to severe CKD 4
• Outdated renal dosing algorithms that cap allopurinol at 300 mg in renal impairment should be abandoned 1
• For creatinine clearance 10-20 mL/min, a maximum daily dose of 200 mg is suitable; for <10 mL/min, do not exceed 100 mg daily 3
• Monitor closely for hypersensitivity reactions when escalating doses in renal impairment 1, 3

Long-Term Monitoring

Once target serum uric acid is achieved, monitor every 6 months to ensure maintenance of target levels and assess adherence. 4, 5

• At each visit, check serum uric acid, assess clinical symptoms, evaluate medication adherence and tolerability, and monitor for adverse effects 5
• Monitor renal function every 6 months, as allopurinol dosing may need adjustment if renal function changes 5
• Watch for hypersensitivity reactions including rash, pruritus, elevated hepatic transaminases, and eosinophilia 4

Duration of Therapy

Lifelong therapy is recommended, as discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years. 4, 1, 5

• The primary goal is to maintain serum uric acid below the saturation point for monosodium urate to promote crystal dissolution and prevent new crystal formation 4, 5
• Do not discontinue allopurinol after achieving symptom control 1, 5

Critical Pitfalls to Avoid

• Never rely solely on the standard 300 mg dose—this fails to achieve target urate levels in more than half of patients 4, 1
• Never discontinue allopurinol after symptom improvement—this leads to recurrence in 87% of patients within 5 years 4, 1
• Never use outdated renal dosing caps—doses can be safely increased above 300 mg with proper monitoring even in renal impairment 1
• Never start at high doses—this dramatically increases the risk of potentially fatal hypersensitivity syndrome 2