When should allopurinol (Uric Acid Lowering Therapy - ULT) be started in a patient with gout who is not currently taking it?

When to Start Allopurinol in Gout Patients

Start allopurinol for patients with frequent gout flares (≥2 per year), presence of tophi, or radiographic damage attributable to gout, and conditionally start it for patients with >1 flare but infrequent attacks (<2/year) or after a first flare with high-risk features (CKD stage ≥3, serum urate >9 mg/dL, or urolithiasis). 1

Strong Indications for Starting Allopurinol

The 2020 American College of Rheumatology guidelines provide clear criteria for when urate-lowering therapy should be initiated:

• Frequent gout flares (≥2 per year): Strongly recommended to start allopurinol 1
• Presence of one or more subcutaneous tophi: Strongly recommended to initiate therapy 1
• Radiographic damage attributable to gout (any imaging modality): Strongly recommended to start allopurinol 1
• Renal stones/urolithiasis: Indicated for allopurinol initiation 1

Conditional Indications for Starting Allopurinol

The following scenarios warrant consideration for starting allopurinol, though the recommendation strength is conditional:

• Patients with >1 previous flare but infrequent attacks (<2/year): Conditionally recommended to start therapy 1
• First gout flare with high-risk comorbidities: Conditionally recommended if the patient has CKD stage ≥3, serum urate >9 mg/dL, or history of urolithiasis 1
• Young patients (<40 years) with first gout flare: Consider initiating therapy close to the time of first diagnosis 2

When NOT to Start Allopurinol

• Asymptomatic hyperuricemia alone (serum urate >6.8 mg/dL with no prior gout flares or tophi): Conditionally recommended AGAINST initiating therapy, as only 20% of patients with serum urate >9 mg/dL develop gout within 5 years 1
• Asymptomatic hyperuricemia with MSU crystal deposition on imaging: Still recommended against treatment in the absence of clinical gout 1

Timing Relative to Acute Flares

A common clinical question is whether to wait for flare resolution before starting allopurinol:

• Starting during an acute flare is conditionally recommended over waiting for flare resolution, as this addresses hyperuricemia sooner and prevents the risk of patients not returning for delayed initiation 1, 3, 2
• Two randomized controlled trials demonstrated that starting allopurinol during an acute attack does not significantly prolong flare duration or worsen severity compared to delayed initiation 4, 5
• The traditional practice of waiting for complete flare resolution is no longer recommended and may lead to delayed appropriate therapy 2

Dosing Strategy When Starting Allopurinol

Start low and go slow to minimize the risk of precipitating flares:

• Starting dose: 100 mg/day for most patients (≤100 mg/day, and lower in patients with CKD stage ≥3) 1, 6
• For patients with severely impaired renal function (CKD stage ≥4): Start as low as 50 mg/day 3, 6
• Dose escalation: Increase by 100 mg increments every 2-5 weeks (or weekly per FDA label) until target serum urate is achieved 3, 6
• Target serum urate: <6 mg/dL (or <5 mg/dL if tophi present) 3, 2
• Maximum dose: 800 mg/day (FDA-approved maximum) 1, 6

The rationale for starting low is that higher initial doses (e.g., standard 300 mg) increase the risk of allopurinol hypersensitivity syndrome and flare precipitation 1. A 2024 study confirmed that starting with allopurinol 100 mg daily was associated with a 3.21-fold increased risk of gout flares in the first six months compared to lower starting doses 7.

Mandatory Prophylaxis When Starting Allopurinol

Always initiate concomitant anti-inflammatory prophylaxis when starting allopurinol:

• Strongly recommended by the American College of Rheumatology to prevent flares during initiation 1, 6
• Options include: Colchicine 0.5-1 mg/day, NSAIDs, or prednisone/prednisolone 1, 3
• Duration: Continue for 3-6 months minimum, with extension beyond 6 months if flares continue 1, 3
• The FDA label specifically states that "maintenance doses of colchicine generally should be given prophylactically when allopurinol tablets are begun" 6

Patients who had a gout flare in the month before starting allopurinol are at particularly high risk (2.65-fold increased odds of flare) and especially benefit from prophylaxis 7.

Monitoring Requirements

• Serum urate levels: Check every 2-5 weeks during dose titration to guide escalation toward target <6 mg/dL 3, 6
• Renal function: Assess before starting and monitor closely during early stages, especially in patients with pre-existing renal disease 6
• Hypersensitivity reactions: Monitor for pruritus, rash, elevated liver enzymes, and eosinophilia during dose escalation 3
• HLA-B*5801 testing: Conditionally recommended in high-risk populations (Korean patients with CKD stage ≥3, Han Chinese, Thai patients) before starting allopurinol 3

Common Pitfalls to Avoid

• Starting at 300 mg daily without checking renal function: This standard dose is too high for initial therapy and increases flare risk 1, 6
• Waiting for complete flare resolution: This delays appropriate therapy and is no longer recommended 2
• Failing to provide prophylaxis: This dramatically increases the risk of flares during the first 3-6 months 1, 6
• Stopping allopurinol during a flare: If already on therapy, continue the current dose to maintain steady urate-lowering effects 2
• Inadequate dose titration: Many patients require >300 mg/day (often 400-600 mg/day) to achieve target serum urate 1, 6