Allopurinol is for Prevention, Not Acute Gout Flares

Allopurinol is a urate-lowering therapy used for long-term prevention of gout attacks, not for treating acute gout flares. 1, 2, 3

Role in Acute Gout Flares

Allopurinol has no anti-inflammatory effect and does not treat the pain or inflammation of an acute gout attack. 1, 2
Acute gout flares must be treated with anti-inflammatory medications: NSAIDs, colchicine, or corticosteroids. 1, 2
The FDA label explicitly states allopurinol is "not recommended for the treatment of asymptomatic hyperuricemia" and warns that initiating therapy can actually increase acute gout attacks. 3

Allopurinol reduces serum uric acid levels over weeks to months by inhibiting xanthine oxidase, which prevents future gout attacks. 1
High-strength evidence shows urate-lowering therapy does not reduce acute attacks in the first 6 months, but moderate-strength evidence demonstrates it reduces flares after approximately 1 year of continuous therapy. 4
Long-term therapy (>1 year) with allopurinol significantly reduces gout flare frequency. 1

The American College of Rheumatology conditionally recommends starting allopurinol during an acute flare (rather than waiting) if anti-inflammatory therapy is provided concurrently. 2
Two small randomized trials (n=51 and n=31) showed that initiating allopurinol at 100-300 mg during acute attacks did not prolong flare duration or worsen severity when patients received concurrent anti-inflammatory treatment. 4, 5, 6
However, EULAR guidelines note these trials were underpowered and do not provide firm conclusions, particularly for more potent urate-lowering regimens. 4

Historically, allopurinol initiation was delayed 2 weeks after flare resolution to avoid triggering or prolonging attacks. 1
This remains a reasonable approach if not starting during the acute phase. 4

Immediately initiate NSAIDs, colchicine, or corticosteroids for symptom relief. 1, 2

Start allopurinol at 100 mg daily (not higher) and increase by 100 mg every 2-4 weeks until serum uric acid <6 mg/dL (360 μmol/L). 4, 1, 3
Mandatory anti-inflammatory prophylaxis with colchicine 0.5-1 mg daily or low-dose NSAIDs must be continued for at least 6 months when starting allopurinol. 4, 1
High-quality evidence from the CONFIRMS trial showed that continuing prophylaxis for 6 months (versus 8 weeks) prevented the spike in flares seen after early discontinuation. 4

Maximum FDA-approved dose is 800 mg daily. 3
Target serum uric acid <6 mg/dL for most patients, or <5 mg/dL for severe gout with tophi. 4
Adjust dose in renal impairment: 200 mg daily if creatinine clearance 10-20 mL/min, ≤100 mg daily if <10 mL/min. 3

Test for HLA-B*5801 allele before starting allopurinol in high-risk populations (Han Chinese, Thai, Korean patients, especially those with CKD stage ≥3) due to increased risk of fatal hypersensitivity reactions. 1, 2
Discontinue allopurinol immediately if any rash develops, as skin reactions can be severe and sometimes fatal (DRESS syndrome). 3
Colchicine prophylaxis dose must be reduced in renal impairment and with concurrent statin use due to neurotoxicity/muscular toxicity risk. 4

Do not use allopurinol to treat acute gout pain—it will not help. 2, 3
Do not start allopurinol at high doses (e.g., 300 mg)—this increases flare risk. 4, 2
Do not initiate allopurinol without concurrent anti-inflammatory prophylaxis. 2
Do not discontinue allopurinol after achieving symptom control—gout will recur. 2
A 2004 randomized trial demonstrated that colchicine prophylaxis during allopurinol initiation reduced total flares (0.52 vs 2.91, p=0.008) and flare severity compared to placebo. 7