What is the recommended first‑line medication for an acute gout attack in an adult, and what alternatives should be used if NSAIDs are contraindicated (e.g., peptic ulcer disease, renal impairment, heart failure)?

Acute Gout Attack Medication

For an acute gout attack, start an NSAID (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) at full dose within 24 hours of symptom onset and continue until complete resolution; if NSAIDs are contraindicated due to peptic ulcer disease, renal impairment, or heart failure, use oral prednisone 30–35 mg daily for 5 days instead. 1, 2, 3

First-Line Treatment Selection Algorithm

When NSAIDs Are Appropriate (No Contraindications)

• Initiate therapy within 24 hours of symptom onset—delays beyond this window markedly reduce effectiveness of all agents 1, 3
• Use full FDA-approved doses throughout the entire attack until complete resolution; do not taper early 1, 3
• FDA-approved NSAIDs for gout:
  • Naproxen 500 mg twice daily 1, 3
  • Indomethacin 50 mg three times daily 1, 3
  • Sulindac 200 mg twice daily 1, 3
• No single NSAID is superior to another—select based on availability and patient tolerance 1, 3

When NSAIDs Are Contraindicated

Absolute contraindications to NSAIDs: 1, 2, 4

• Severe renal impairment (eGFR <30 mL/min)—NSAIDs can precipitate or worsen acute kidney injury
• Active or recent gastrointestinal bleeding
• Heart failure—NSAIDs increase cardiovascular risk and fluid retention
• Peptic ulcer disease (active)
• Patients on anticoagulation therapy

First alternative: Oral corticosteroids 1, 2

• Prednisone 30–35 mg once daily for 5 days (fixed dose, no taper needed for short course) 2
• Alternative regimen: 0.5 mg/kg/day for 5–10 days at full dose then stop, OR 2–5 days at full dose followed by 7–10 day taper 2
• Level A evidence shows corticosteroids are equally effective as NSAIDs but with significantly fewer adverse events (27% vs 63% with indomethacin) 2, 3
• No dose adjustment required for renal impairment—making corticosteroids the safest first-line option in CKD 2, 4

Second alternative: Colchicine (if started ≤36 hours from symptom onset) 1, 5

• Loading dose: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg) 1, 5
• After 12-hour pause: Resume 0.6 mg once or twice daily until attack resolves 1, 5
• Critical timing: Colchicine is ineffective if started >36 hours after symptom onset 1
• Absolute contraindications to colchicine: 1, 5
  • Severe renal impairment (CrCl <30 mL/min)—risk of fatal toxicity
  • Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil)—especially with any degree of renal or hepatic impairment
  • Combined renal and hepatic impairment with any P-gp/CYP3A4 inhibitor

Special Populations & Contraindication Management

Peptic Ulcer Disease

• Avoid NSAIDs entirely—use prednisone 30–35 mg daily for 5 days as first-line 2
• If NSAID must be used, combine with proton pump inhibitor, though corticosteroids remain safer 1, 6

Renal Impairment (eGFR <30 mL/min)

• Prednisone is the safest first-line option—no dose adjustment required 2, 4
• Avoid NSAIDs completely—they can precipitate acute kidney injury 4
• Avoid colchicine in severe renal impairment—fatal toxicity risk 1, 4
• For monoarticular gout, intra-articular corticosteroid injection (triamcinolone 40 mg for knee, 20–30 mg for ankle) is an excellent alternative 1, 2

Heart Failure

• Colchicine is considered safe and may reduce risk of myocardial infarction 7
• Avoid NSAIDs—they worsen fluid retention and increase cardiovascular risk 1, 7
• Short-course low-dose glucocorticoids (prednisone 30–35 mg for 5 days) are efficacious and may be safe 2, 7

Cardiovascular Disease

• Colchicine is preferred—potentially reduces myocardial infarction risk 7
• Avoid NSAIDs—increase cardiovascular events 7
• Corticosteroids are acceptable for short courses 2, 7

Severe or Polyarticular Attacks (≥4 Joints Involved)

Consider combination therapy: 1

• Colchicine + NSAID (provides synergistic anti-inflammatory effects) 1
• Oral corticosteroid + colchicine 1
• Intra-articular steroid + any oral agent 1
• Avoid combining NSAIDs with systemic corticosteroids—synergistic gastrointestinal toxicity 1

Critical Pitfalls to Avoid

• Do not delay treatment beyond 24 hours—efficacy drops sharply 1, 3
• Do not use colchicine after 36 hours from symptom onset—it becomes ineffective 1
• Do not taper NSAIDs early—maintain full dose until complete resolution 1, 3
• Do not stop ongoing urate-lowering therapy (allopurinol, febuxostat) during an acute flare—continue without interruption 1
• Do not use the obsolete high-dose colchicine regimen (0.5 mg every 2 hours)—causes severe diarrhea in most patients with no additional benefit 1
• Do not combine colchicine with verapamil—life-threatening toxicity, multiorgan failure, and death can occur 1

Monitoring & Inadequate Response

Define inadequate response as: 1

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

If inadequate response occurs: 1

• Consider alternative diagnosis
• Switch to another monotherapy agent
• Add a second agent (combination therapy)

Long-Term Prophylaxis Considerations

• When initiating urate-lowering therapy (allopurinol, febuxostat), provide colchicine prophylaxis 0.6 mg once or twice daily for at least 6 months to prevent recurrent flares 1, 5
• Alternative prophylaxis options if colchicine contraindicated: low-dose NSAID with PPI, or low-dose prednisone (<10 mg/day) 1, 2