Indomethacin for Acute Gout
Indomethacin 50 mg three times daily for 2–3 days, followed by 25 mg three times daily for an additional 3–5 days, is an effective regimen for acute gout in adults with normal renal and hepatic function, but corticosteroids (prednisone 30–35 mg daily for 5 days) are now preferred as first-line therapy because they provide equivalent pain relief with significantly fewer adverse events. 1, 2, 3
Standard Indomethacin Dosing Regimen
Initial phase: Start indomethacin 50 mg orally three times daily for 2–3 days at the onset of an acute gout attack. 2
Taper phase: Reduce to 25 mg three times daily for an additional 3–5 days until symptoms resolve, with total treatment duration typically 5–7 days. 2
Timing is critical: Initiate treatment within 24 hours of symptom onset for optimal efficacy; effectiveness drops significantly beyond this window. 2
Pain relief timeline: Significant improvement typically occurs within 24–36 hours, though this is slower than intramuscular corticosteroids (3 hours) or ACTH (3 hours). 2, 4
Why Corticosteroids Are Now Preferred Over Indomethacin
Equivalent efficacy, superior safety: Oral prednisolone 30–35 mg daily for 5 days provides pain relief comparable to indomethacin but with markedly fewer adverse events—only 27% of prednisolone patients reported adverse events versus 63% in the indomethacin group. 1, 3
Gastrointestinal toxicity: Indomethacin causes gastrointestinal adverse events in 55–63% of patients, including abdominal discomfort, dyspepsia, and risk of GI bleeding, compared to significantly lower rates with corticosteroids. 2, 4, 3
Guideline consensus: The American College of Rheumatology and European League Against Rheumatism now recommend corticosteroids as first-line therapy in patients without contraindications because they are safer, lower cost, and equally effective. 1
Absolute Contraindications to Indomethacin
Severe renal impairment (eGFR <30 mL/min): NSAIDs can precipitate or worsen acute kidney injury; corticosteroids are the safest first-line option in this population. 1, 2
Active or recent gastrointestinal bleeding: NSAIDs increase bleeding risk and are absolutely contraindicated. 5
Heart failure: NSAIDs cause fluid retention and can exacerbate heart failure; corticosteroids are preferred. 1, 2
Cirrhosis or hepatic impairment: NSAIDs are contraindicated; use corticosteroids instead. 1, 2
Patients on anticoagulation therapy: NSAIDs significantly increase bleeding risk; corticosteroids or colchicine are safer alternatives. 1, 5
Adjustments for Elderly Patients
Avoid indomethacin in elderly patients with renal impairment: Age-related decline in renal function makes NSAIDs particularly hazardous; elderly patients are at increased risk of adverse effects including acute kidney injury, GI bleeding, and cardiovascular events. 5, 6
Preferred alternative: Prednisone 30–35 mg daily for 5 days requires no dose adjustment for age or renal function and is safer in elderly patients with multiple comorbidities. 1
If NSAIDs must be used in elderly patients: Select agents with rapid absorption and short half-life to avoid accumulation in subclinical renal impairment, but indomethacin is not the optimal choice. 6
Adjustments for Renal Impairment
Mild to moderate renal impairment (CrCl 30–80 mL/min): Use indomethacin with extreme caution and close monitoring; consider dose reduction or switch to corticosteroids. 5, 6
Severe renal impairment (eGFR <30 mL/min): Do not use indomethacin. Switch to prednisone 30–35 mg daily for 5 days, which requires no dose adjustment and is the safest first-line option. 1, 2
Colchicine alternative: If corticosteroids are contraindicated, colchicine 1.2 mg followed by 0.6 mg one hour later can be used in mild to moderate renal impairment, but avoid in severe renal impairment (CrCl <30 mL/min). 5
Alternative First-Line Options (Preferred Over Indomethacin)
Oral Corticosteroids (First Choice)
Prednisone 0.5 mg/kg per day (approximately 30–35 mg for average adults) for 5–10 days at full dose, then stop abruptly, OR give for 2–5 days at full dose followed by a 7–10 day taper. 1
Advantages: No dose adjustment needed for renal impairment, safer in cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, and anticoagulation. 1
Contraindications: Systemic fungal infections (absolute), uncontrolled diabetes (relative—monitor glucose closely), active infection (relative). 1
Colchicine (If Started Early)
Colchicine 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg), then 0.6 mg once or twice daily until attack resolves. 5
Critical timing: Must be started within 36 hours of symptom onset; effectiveness drops significantly beyond this window. 5
Contraindications: Severe renal impairment (CrCl <30 mL/min), concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole). 5
Intramuscular Corticosteroids (For NPO Patients or Rapid Relief)
Triamcinolone acetonide 60 mg IM as a single injection provides pain relief within 3 hours, faster than oral agents. 1
Indications: Patients who are NPO due to surgery or medical conditions, inability to tolerate oral medications, or need for rapid pain relief. 1
Common Pitfalls to Avoid
Continuing high-dose indomethacin beyond 2–3 days increases adverse effects without additional benefit. Taper to 25 mg three times daily after the initial phase. 2
Failing to assess renal function before prescribing indomethacin: NSAIDs can cause acute kidney injury in patients with unrecognized renal impairment. 1, 2
Combining NSAIDs with systemic corticosteroids: This combination causes synergistic gastrointestinal toxicity and should be avoided. 5
Interrupting ongoing urate-lowering therapy during an acute attack: Continue allopurinol or febuxostat during flares; stopping does not improve outcomes and may prolong disease course. 1, 2
Failing to provide prophylaxis when initiating urate-lowering therapy: Start colchicine 0.6 mg once or twice daily for at least 6 months when beginning allopurinol or febuxostat to prevent recurrent flares. 5, 2
Treatment Algorithm for Acute Gout
Confirm diagnosis (ideally with joint aspiration showing monosodium urate crystals, though clinical diagnosis is acceptable). 1
Assess renal function, cardiovascular risk, GI risk, and medication interactions before selecting therapy. 1, 5
First-line choice:
- Normal renal function, no GI/CV risk: Prednisone 30–35 mg daily for 5 days OR indomethacin 50 mg three times daily for 2–3 days, then 25 mg three times daily for 3–5 days. 1, 2
- Renal impairment, CV disease, heart failure, cirrhosis, GI risk, or anticoagulation: Prednisone 30–35 mg daily for 5 days (no dose adjustment needed). 1
- Early presentation (<36 hours) with normal renal function: Colchicine 1.2 mg followed by 0.6 mg one hour later is an alternative. 5
Severe attacks (polyarticular, multiple large joints): Consider combination therapy—colchicine + NSAID, prednisone + colchicine, or intra-articular corticosteroids + oral agent. 1, 5
Monitor response: Inadequate response is defined as <20% pain improvement within 24 hours OR <50% improvement at ≥24 hours; consider alternative diagnosis or add second agent. 1
Continue ongoing urate-lowering therapy during the acute attack; do not interrupt allopurinol or febuxostat. 1, 2