How should an acute gout flare be treated, selecting the appropriate anti‑inflammatory based on the patient’s comorbidities and renal function?

How to Treat Gout Pain

For an acute gout flare, initiate therapy within 24 hours using NSAIDs, colchicine, or oral corticosteroids as first-line monotherapy, selecting the agent based on renal function, cardiovascular risk, gastrointestinal comorbidities, and drug interactions. 1, 2

Immediate Treatment Selection Algorithm

Step 1: Assess Renal Function First

• If eGFR < 30 mL/min (severe renal impairment): Use oral prednisone 30–35 mg daily for 5 days as the only safe option; both NSAIDs and colchicine are absolutely contraindicated due to risks of acute kidney injury and fatal toxicity. 1, 2

• If eGFR 30–59 mL/min (moderate renal impairment): Oral corticosteroids remain the safest choice; NSAIDs carry high risk of worsening renal function, and colchicine requires dose reduction to 0.6 mg once daily with close monitoring. 1, 2

• If eGFR ≥ 60 mL/min (normal renal function): All three drug classes are options—proceed to Step 2. 1, 2

Step 2: Check for Drug Interactions (Colchicine Contraindications)

• If the patient is taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil), colchicine is absolutely contraindicated due to risk of fatal toxicity, especially with any degree of renal or hepatic impairment. 1, 2, 3

• If these inhibitors are present, choose NSAIDs or corticosteroids instead. 1, 2

Step 3: Evaluate Cardiovascular and Gastrointestinal Risk (NSAID Contraindications)

• Avoid NSAIDs if the patient has:

  • Heart failure or established cardiovascular disease 1, 2
  • Active or recent peptic ulcer disease or gastrointestinal bleeding 1, 2
  • Cirrhosis or hepatic impairment 1, 2
  • Current anticoagulation therapy 1, 2

• In these scenarios, use oral prednisone 30–35 mg daily for 5 days or colchicine (if no drug interactions). 1, 2

Step 4: Consider Timing from Symptom Onset

• If ≤ 36 hours since symptom onset: Colchicine is most effective when started within 12 hours and should not be initiated after 36 hours. 1, 2

• If > 36 hours since symptom onset: Do not use colchicine; select NSAIDs or corticosteroids instead. 1, 2

Specific Dosing Regimens

Colchicine (When Appropriate)

• Loading dose: 1.2 mg orally at first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg over 1 hour). 1, 2

• Maintenance: After a 12-hour pause, resume 0.6 mg once or twice daily until the attack resolves. 1, 2

• This low-dose regimen achieves ≥50% pain reduction with a number-needed-to-treat of 3–5 and causes significantly fewer gastrointestinal adverse effects (23% diarrhea) compared to obsolete high-dose regimens (77% diarrhea). 1, 2

• Critical timing: Maximum efficacy occurs when started within 12 hours; do not initiate after 36 hours from symptom onset. 1, 2

NSAIDs (When Appropriate)

• Use full FDA-approved anti-inflammatory doses for the entire attack without early tapering:

  • Naproxen 500 mg twice daily 1, 2
  • Indomethacin 50 mg three times daily 1, 2
  • Sulindac 200 mg twice daily 1, 2

• No single NSAID has demonstrated superior efficacy; selection should be based on availability and individual tolerance. 1, 2

• Add a proton-pump inhibitor in patients with gastrointestinal risk factors. 1, 2

Oral Corticosteroids (When Appropriate)

• Prednisone 30–35 mg once daily for 5 days, then stop abruptly (no taper needed for short courses). 1, 2

• Alternative regimen: Prednisone 0.5 mg/kg/day for 5–10 days, followed by either abrupt cessation or a 7–10 day taper. 1, 2

• Oral corticosteroids provide Level A evidence of efficacy equivalent to NSAIDs but with fewer adverse events (27% vs 63%). 1, 2

• Absolute contraindication: Active systemic fungal infection. 1, 2

Intra-articular Corticosteroid Injection (For Monoarticular Gout)

• For involvement of 1–2 large, accessible joints:

  • Triamcinolone acetonide 40 mg for the knee 1, 2
  • Triamcinolone acetonide 20–30 mg for the ankle 1, 2

• This provides targeted control with minimal systemic effects. 1, 2

Intramuscular Corticosteroids (When Oral Route Unavailable)

• Triamcinolone acetonide 60 mg as a single intramuscular injection is effective for patients unable to take oral medications (NPO status, surgical conditions). 1, 2

Combination Therapy for Severe or Polyarticular Attacks

• Indications for combination therapy:

  • Polyarticular gout (≥4 joints involved) 1, 2
  • Multiple large joints affected 1, 2
  • Severe pain unresponsive to monotherapy within 24 hours 1, 2

• Recommended combinations:

  • Colchicine + NSAID 1, 2
  • Oral corticosteroid + colchicine 1, 2
  • Intra-articular steroid + any oral agent 1, 2

• Avoid systemic NSAID + systemic corticosteroid due to synergistic gastrointestinal toxicity. 1, 2

Management of Ongoing Urate-Lowering Therapy

• Do not discontinue existing allopurinol or febuxostat during an acute flare; continue the urate-lowering therapy and treat the flare separately. 4, 1, 2

• Do not initiate new urate-lowering therapy during an acute flare; wait until the attack has completely resolved. 1, 2

Common Pitfalls to Avoid

• Do not delay treatment beyond 24 hours; effectiveness of all agents declines sharply after this window. 1, 2

• Do not initiate colchicine after 36 hours from symptom onset; efficacy drops dramatically. 1, 2

• Do not taper NSAIDs early; maintain full dose throughout the entire attack until complete resolution. 1, 2

• Do not use obsolete high-dose colchicine regimens (e.g., 0.5 mg every 2 hours); they cause severe diarrhea in most patients without added benefit. 1, 2

• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment due to fatal toxicity risk. 1, 2, 3

• Do not prescribe NSAIDs to patients with severe renal impairment, heart failure, active peptic ulcer disease, or those on anticoagulation. 1, 2

Monitoring Response

• Define inadequate response as:

  • <20% improvement in pain within 24 hours, OR 1
  • <50% improvement at ≥24 hours after initiating therapy 1

• If inadequate response occurs, consider alternative diagnoses, switch to another monotherapy, or add a second agent. 1