What is the recommended dose and frequency for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and other medications in the treatment of acute gout, particularly in patients with Impaired renal function or those who cannot tolerate NSAIDs?

Treatment of Acute Gout: Dosing and Frequency

For acute gout, use NSAIDs at full anti-inflammatory doses (naproxen 750 mg initial dose, then 250 mg every 8 hours until attack resolves), colchicine 1.2 mg followed by 0.6 mg one hour later (only if started within 36 hours of symptom onset), or corticosteroids (prednisone 30-35 mg daily for 3-5 days), with dose adjustments required for renal impairment. 1

NSAIDs: Dosing and Frequency

FDA-Approved Regimens

For acute gout, naproxen should be dosed at 750 mg initially, followed by 250 mg every 8 hours until the attack subsides. 2 This represents the FDA-approved dosing strategy for acute gout attacks. 2

• Indomethacin is FDA-approved at full anti-inflammatory doses for acute gout 1
• Sulindac is also FDA-approved for acute gout treatment 1
• Other NSAIDs at analgesic/anti-inflammatory doses may be equally effective 1

Duration and Tapering

Continue the NSAID at full dose until the acute gouty attack completely resolves; do not taper prematurely. 1 The American College of Rheumatology emphasizes maintaining full-dose therapy throughout the attack rather than early dose reduction. 1

Special Populations: Renal Impairment

NSAIDs are contraindicated in patients with moderate to severe renal impairment (creatinine clearance <30 mL/min). 2 For patients with mild renal impairment, dose tapering should be considered with close monitoring for multiple comorbidities. 1

COX-2 Inhibitors Alternative

For patients with gastrointestinal contraindications to traditional NSAIDs, celecoxib can be used at 800 mg once, followed by 400 mg on day 1, then 400 mg twice daily for one week, though the risk-benefit ratio remains unclear. 1

Colchicine: Dosing and Frequency

Standard Acute Gout Dosing

Colchicine should be dosed as 1.2 mg loading dose followed by 0.6 mg one hour later, but ONLY if treatment begins within 36 hours of symptom onset. 1 This low-dose regimen has comparable efficacy to high-dose regimens with significantly fewer adverse effects. 1

After the initial loading doses, continue with 0.6 mg once or twice daily starting 12 hours after the second dose until the attack resolves. 1

Critical Timing Limitation

Colchicine loses effectiveness if not started within 36 hours of attack onset, making it inappropriate for delayed presentations. 1

Renal Impairment Adjustments

For severe renal impairment (CrCl <30 mL/min): The treatment dose remains 1.2 mg followed by 0.6 mg one hour later, but repeat courses should occur no more than once every two weeks. 3

For dialysis patients: Reduce the total dose to a single 0.6 mg tablet, with treatment courses repeated no more than once every two weeks. 3

For prophylaxis in severe renal impairment: Start at 0.3 mg daily with careful dose escalation monitoring. 3

For dialysis patients on prophylaxis: Use 0.3 mg twice weekly. 3

Drug Interactions Requiring Dose Reduction

When colchicine is combined with strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ritonavir, or other protease inhibitors), the acute gout dose must be reduced to 0.6 mg × 1 dose, followed by 0.3 mg one hour later, with repeat dosing no earlier than 3 days. 3

Patients with renal or hepatic impairment should NOT receive colchicine with these interacting drugs. 3

Corticosteroids: Dosing and Frequency

Oral Corticosteroid Regimens

Prednisone should be dosed at 0.5 mg/kg per day (approximately 30-35 mg for average adults) for 5-10 days at full dose then stopped abruptly, OR given for 2-5 days at full dose followed by a 7-10 day taper. 4, 5 This represents Level A evidence from the American College of Rheumatology. 5

The American College of Rheumatology recommends the non-tapered approach (5-10 days full dose then stop) for straightforward monoarticular cases without significant comorbidities. 5 For severe attacks, polyarticular involvement, or patients at higher risk for rebound flares, use the tapered approach. 5

Intramuscular Corticosteroids

For patients who cannot take oral medications or require rapid systemic effect, use intramuscular triamcinolone acetonide 60 mg as a single injection. 4, 5 This provides effective treatment comparable to oral NSAIDs with fewer adverse effects. 6

Intra-articular Corticosteroids

When only 1-2 large joints are involved, perform arthrocentesis and inject triamcinolone acetonide 40 mg into large joints like the knee. 4, 5 This approach is highly effective and avoids systemic side effects. 4, 5

Corticosteroids in Renal Impairment

Corticosteroids are the safest first-line option for acute gout in patients with renal impairment, as NSAIDs can cause acute kidney injury and colchicine toxicity is significantly increased in chronic kidney disease. 5 Use prednisone 30-35 mg daily for 3-5 days, with the option to taper over 7-10 days for patients at higher risk of rebound. 5

Treatment Selection Algorithm

Step 1: Assess Contraindications

• Renal impairment (CrCl <30 mL/min): Avoid NSAIDs; use corticosteroids as first-line 4, 5
• Cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, or anticoagulation: Prefer corticosteroids over NSAIDs 5
• Uncontrolled diabetes, active infection, or recent GI bleeding: Avoid corticosteroids 4
• Strong CYP3A4 inhibitor use: Reduce colchicine dose or avoid 3

Step 2: Assess Timing and Joint Involvement

• Symptom onset >36 hours: Colchicine is ineffective; choose NSAIDs or corticosteroids 1
• 1-2 large joints involved: Consider intra-articular corticosteroid injection 4, 5
• Polyarticular involvement: Use oral corticosteroids or NSAIDs 4, 5

Step 3: Select Initial Therapy

First-line options (no specific NSAID is preferred over another): 1

• Naproxen 750 mg, then 250 mg every 8 hours 2
• Colchicine 1.2 mg followed by 0.6 mg one hour later (if <36 hours from onset) 1
• Prednisone 30-35 mg daily for 3-5 days 4, 5
• Intra-articular triamcinolone 40 mg (for 1-2 joints) 4, 5

Step 4: Consider Combination Therapy

For severe pain with polyarticular involvement, use combination therapy: oral corticosteroids plus colchicine, or intra-articular steroids with any oral modality. 1, 7, 5

Critical Monitoring and Pitfalls

Inadequate Response Definition

Inadequate response is defined as <20% improvement in pain within 24 hours OR <50% improvement at ≥24 hours after initiating therapy. 7, 5 If this occurs, consider combination therapy or alternative agents. 7, 5

Common Pitfalls to Avoid

• Do NOT interrupt ongoing urate-lowering therapy during an acute attack 4, 7, 5
• Do NOT use colchicine for attacks presenting >36 hours after symptom onset 1
• Do NOT use standard colchicine doses without adjustment in severe renal impairment or with strong CYP3A4 inhibitors 3
• Do NOT taper NSAIDs prematurely; continue full dose until complete attack resolution 1
• Do NOT use high-dose prednisone (>10 mg/day) for prophylaxis during urate-lowering therapy initiation 5

Monitoring Requirements

• Monitor renal function closely in patients with demonstrated susceptibility to drug-induced AKI 4
• Check blood glucose in diabetic patients on corticosteroids 5
• Assess for drug interactions before prescribing colchicine 3

Prophylaxis During Urate-Lowering Therapy

Once the acute attack resolves and urate-lowering therapy is initiated, provide prophylaxis with colchicine 0.6 mg once or twice daily for at least 6 months, or for 3 months after achieving target uric acid levels without tophi. 7 In patients with renal impairment history, use colchicine only after renal function normalizes with appropriate dose adjustment. 4

Low-dose prednisone (<10 mg/day) can be used as second-line prophylaxis if colchicine and NSAIDs are contraindicated. 5