Concurrent NSAIDs and Colchicine for Pseudogout
Yes, providers can and should prescribe NSAIDs and colchicine concurrently for pseudogout attacks, particularly for severe presentations involving multiple joints or polyarticular arthritis. 1, 2
Evidence Supporting Combination Therapy
The American College of Rheumatology explicitly recommends combination therapy with colchicine and NSAIDs as an appropriate first-line option for acute crystal arthropathy attacks, including pseudogout. 1 This recommendation applies particularly to:
- Severe attacks involving multiple large joints 1, 2
- Polyarticular arthritis presentations 1, 2
- Patients not responding adequately to monotherapy 1
The combination provides synergistic anti-inflammatory effects by targeting different inflammatory pathways—colchicine inhibits microtubule polymerization and neutrophil migration, while NSAIDs block prostaglandin synthesis through COX inhibition. 2
Dosing Recommendations
Colchicine Dosing
- Initial loading: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg over one hour) 2
- Continuation: 0.6 mg once or twice daily until attack resolves, starting at least 12 hours after the initial loading dose 1, 2
NSAID Dosing
- Use full FDA-approved doses until the attack completely resolves 2
- FDA-approved options include naproxen, indomethacin, and sulindac 2
- No single NSAID has proven superior to others for efficacy 2
Critical Safety Considerations
Absolute Contraindications for Colchicine
Do not prescribe colchicine to patients concurrently taking strong CYP3A4 or P-glycoprotein inhibitors (such as clarithromycin, erythromycin, or cyclosporine), especially if they also have renal or hepatic impairment. 2, 3 This combination can cause life-threatening toxicity including pancytopenia, multiorgan failure, and cardiac arrhythmias. 3
NSAID Precautions
Use NSAIDs cautiously in patients with: 2
- Renal disease (GFR <30 mL/min)
- Heart failure
- Cirrhosis
- Active peptic ulcer disease
- Concurrent anticoagulation
Important Caveat About Corticosteroids
The American College of Rheumatology task force did not vote on combining NSAIDs with systemic corticosteroids due to concerns about synergistic gastrointestinal toxicity. 1 However, combining colchicine with NSAIDs does not carry this same concern.
When to Use Combination Therapy
Start with combination therapy immediately if: 1, 2
- Multiple large joints are involved
- Polyarticular presentation
- Severe pain and inflammation
Add a second agent if monotherapy fails to achieve: 1
- At least 20% pain improvement within 24 hours
- At least 50% improvement at 24 hours
Alternative Options
If colchicine and NSAIDs are both contraindicated or ineffective: 1
- Oral corticosteroids: Prednisone 0.5 mg/kg/day (approximately 30-35 mg) for 5-10 days 2, 4
- Intra-articular corticosteroid injection: For monoarticular or oligoarticular involvement 2, 4
- Intramuscular triamcinolone acetonide: 60 mg as single injection 4
Common Pitfalls to Avoid
- Delaying treatment beyond 36 hours significantly reduces colchicine effectiveness 2
- Using high-dose colchicine regimens (>1.8 mg in first hour) provides no additional benefit but substantially increases gastrointestinal toxicity 2
- Failing to check for drug interactions before prescribing colchicine, particularly with macrolide antibiotics, azole antifungals, and immunosuppressants 2, 3
- Continuing ineffective monotherapy without escalating to combination therapy in severe cases 1
Evidence Quality Note
While the specific evidence for pseudogout is more limited than for gout, colchicine has demonstrated effectiveness for pseudogout prophylaxis (reducing attacks from 3.2 to 1.0 per patient per year). 5 The American College of Rheumatology guidelines for acute gout management explicitly state that combination therapy with colchicine and NSAIDs is appropriate and carries Evidence C level support. 1