Why Allopurinol Should Not Be Started During Acute Gout (Historical Concern Now Revised)
The traditional teaching to avoid starting allopurinol during an acute gout flare is outdated—current evidence and guidelines now support initiating allopurinol during the acute attack, provided you simultaneously treat with anti-inflammatory therapy and use prophylaxis. 1, 2
The Historical Rationale (Now Disproven)
The old concern was that starting allopurinol during an acute flare would:
- Prolong or worsen the acute attack by causing rapid fluctuations in serum urate levels, which could mobilize urate crystals from tissue deposits and trigger additional inflammation 3, 4
- Cause "information overload" for patients trying to understand both acute flare management and long-term preventive therapy simultaneously 1
However, this concern has been directly refuted by multiple randomized controlled trials showing no significant prolongation of flare duration or worsening of severity when allopurinol is started during acute attacks. 5, 6, 7
Current Evidence-Based Recommendations
The 2020 American College of Rheumatology Position
The ACR now conditionally recommends starting allopurinol during a gout flare rather than waiting for resolution, based on several key advantages: 1, 2
- Time efficiency: Initiating therapy during the flare visit prevents patients from being lost to follow-up 1
- Patient motivation: Patients experiencing acute symptoms are highly motivated to start preventive therapy 1, 2
- No harm demonstrated: Two RCTs showed starting allopurinol during flares does not extend flare duration or severity 1, 5, 6
Critical Requirements When Starting During a Flare
If you choose to initiate allopurinol during an acute attack, you must follow these steps:
Treat the acute inflammation first with therapeutic doses of NSAIDs, colchicine (1.2 mg followed by 0.6 mg one hour later), or corticosteroids 1, 2, 8
Start allopurinol at a low dose (100 mg daily, or 50 mg daily if CKD stage ≥4) to minimize triggering additional flares 2, 9, 3
Provide mandatory anti-inflammatory prophylaxis with colchicine 0.5-1 mg daily (or low-dose NSAIDs if colchicine contraindicated) for at least 3-6 months 1, 2, 3
Titrate slowly: Increase allopurinol by 100 mg every 2-5 weeks until serum urate <6 mg/dL is achieved 1, 2, 8
Why the FDA Label Still Warns About Flares
The FDA label states that "an increase in acute attacks of gout has been reported during the early stages of administration" 3, which reflects the well-established phenomenon that:
- Any initiation or dose escalation of urate-lowering therapy can precipitate flares due to mobilization of urate from tissue deposits 3, 4
- This risk exists whether you start during or after a flare resolves—the timing of initiation relative to the flare does not change this risk 5, 10, 6
- The solution is prophylaxis, not delaying initiation 1, 3
Common Pitfalls to Avoid
Do not start allopurinol at 300 mg daily: The standard dose is too high for initiation and increases flare risk and hypersensitivity reactions 9, 8, 3
Do not skip prophylaxis: Starting allopurinol without concurrent anti-inflammatory prophylaxis dramatically increases the risk of precipitating additional attacks 9, 3
Do not stop prophylaxis early: Continuing for less than 3 months shows significantly less benefit than 6-month prophylaxis 1, 9
Do not assume 300 mg is sufficient: More than half of patients require doses >300 mg to reach target serum urate <6 mg/dL 1, 9
Do not measure serum urate during the acute flare for baseline: Serum urate often falls during acute attacks, producing misleadingly "normal" values that do not reflect true hyperuricemia 2
When Starting During a Flare Is Most Appropriate
Strong indications (start regardless of flare status): 2
- ≥2 gout flares per year
- Any subcutaneous tophi present
- Radiographic damage from gout
Conditional indications (consider starting even during first flare): 2
- Chronic kidney disease stage ≥3
- Serum urate >9 mg/dL (measured between flares)
- History of urolithiasis
The Bottom Line
The reason we historically avoided starting allopurinol during acute gout was fear of prolonging the attack—but this fear has been proven unfounded by rigorous trials. 5, 6, 7 The real risk is precipitating future flares during any ULT initiation (whether during or after an acute attack), which is why prophylaxis is mandatory, not delayed initiation. 1, 3 Starting during the flare offers practical advantages in adherence and patient motivation without causing harm, provided you follow the protocol of low-dose initiation with concurrent anti-inflammatory therapy. 1, 2