Can indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID)) and steroids, such as prednisone, be used simultaneously for the management of an acute gout flare?

Management of Acute Gout Flare: Combined Use of Indomethacin and Steroids

Both indomethacin and steroids can be used simultaneously for acute gout flares, especially in severe cases with polyarticular involvement, though they are typically recommended as individual first-line options rather than in combination for most cases. 1

First-Line Treatment Options for Acute Gout

The American College of Physicians (ACP) strongly recommends three effective first-line treatments for acute gout flares 2:

1. Corticosteroids - Generally considered safer and more cost-effective
2. NSAIDs (including indomethacin)
3. Colchicine

The choice between these options depends on patient-specific factors such as comorbidities and contraindications.

When to Consider Combination Therapy

While monotherapy is typically sufficient for most gout flares, combination therapy may be appropriate in specific situations:

• Severe polyarticular involvement - A combination of two therapeutic modalities at full doses may be considered, including NSAIDs + colchicine or oral corticosteroids + colchicine 1
• Inadequate response to monotherapy - When a single agent fails to provide adequate relief

Indomethacin Considerations

Indomethacin is a potent NSAID that:

• Inhibits prostaglandin synthesis 3
• Is readily absorbed, reaching peak plasma concentrations in about 2 hours 3
• Has nearly 100% bioavailability 3

Contraindications and Cautions for Indomethacin

• Renal disease
• Heart failure
• Cirrhosis
• History of peptic ulcer disease or GI bleeding 2, 1

Steroid Considerations

Corticosteroids (such as prednisone):

• Are generally safer and more cost-effective than NSAIDs 2
• Prednisolone at 35 mg for 5 days has been successfully used to treat acute gout 2
• May be preferred in elderly patients due to favorable safety profile 1

Contraindications and Cautions for Steroids

• Systemic fungal infections
• Potential adverse effects with long-term use include dysphoria, mood disorders, elevated blood glucose, immune suppression, and fluid retention 2

Treatment Algorithm for Acute Gout

1. Assess patient for contraindications to both medications:

   • Check renal function (avoid NSAIDs if eGFR < 30 ml/min) 1
   • Evaluate gastrointestinal risk factors
   • Check for drug interactions

2. For mild to moderate gout flares affecting 1-2 joints:

   • Choose a single agent based on patient factors:
     • Prednisone 30-35 mg daily for 3-5 days 1 OR
     • Indomethacin (typical dosing 50 mg three times daily) 4 OR
     • Colchicine (1.2 mg initially, followed by 0.6 mg one hour later) 1

3. For severe polyarticular gout flares:

   • Consider combination therapy with:
     • Indomethacin + prednisone at full doses 1
     • Monitor closely for adverse effects

Monitoring and Safety

When using combination therapy:

• Monitor for increased risk of adverse events, particularly gastrointestinal effects
• Consider gastroprotection with proton pump inhibitors when using indomethacin
• Monitor blood glucose when using steroids, especially in diabetic patients
• Limit duration of combination therapy to the shortest effective period

Comparative Efficacy

• Moderate-quality evidence shows that NSAIDs and systemic glucocorticoids are probably equally beneficial for pain relief, improvement in function, and treatment success 5
• NSAIDs probably result in more total adverse events compared to glucocorticoids 5

Common Pitfalls to Avoid

• Failing to assess renal function before initiating indomethacin
• Using combination therapy for mild cases where monotherapy would be sufficient
• Prolonged use of either medication beyond the acute phase
• Not considering drug interactions that may increase toxicity risk
• Overlooking the need for prophylaxis when initiating urate-lowering therapy 1, 6