Co-administration of Allopurinol and Colchicine in Gout Management
Yes, patients with gout can and should take allopurinol and colchicine together when initiating urate-lowering therapy, as colchicine provides essential prophylaxis against acute gout flares that commonly occur during the early stages of allopurinol treatment. 1, 2
Rationale for Combination Therapy
Allopurinol and colchicine serve different purposes in gout management:
- Allopurinol: Long-term urate-lowering therapy that reduces serum uric acid levels by inhibiting xanthine oxidase
- Colchicine: Anti-inflammatory agent used for prophylaxis against acute gout flares during initiation of urate-lowering therapy
When starting allopurinol, patients frequently experience an increase in acute gout attacks, even when normal or subnormal serum uric acid levels are achieved. This occurs due to mobilization of urate deposits from tissues, which can cause fluctuations in serum uric acid levels 1.
Evidence Supporting Combination
High-quality evidence demonstrates that prophylaxis with colchicine reduces the risk of acute gout attacks in patients initiating urate-lowering therapy 3:
- A randomized, placebo-controlled trial showed that patients receiving colchicine prophylaxis experienced significantly fewer gout flares (33% vs 77%, P = 0.008) during the first 6 months of allopurinol therapy 4
- In large clinical trials (FACT, APEX, CONFIRMS), the number of acute attacks doubled after discontinuation of prophylaxis at 8 weeks 3
Recommended Dosing
Allopurinol:
- Start with a low dose (100 mg daily)
- Increase by 100 mg increments every 2-4 weeks
- Target serum uric acid level <6 mg/dL for most patients, <5 mg/dL for severe tophaceous gout 2
- Maximum recommended dose: 800 mg daily 1
Colchicine for Prophylaxis:
- 0.6 mg once or twice daily
- Maximum recommended dose: 1.2 mg/day 5
Duration of Prophylaxis
Moderate-strength evidence suggests that prophylaxis should continue for more than 8 weeks 3:
- The rate of acute gout flares approximately doubled when anti-inflammatory prophylaxis was discontinued after 8 weeks 3
- No spike in attacks was observed in trials that continued prophylaxis for the entire 6 months 3
- The European League Against Rheumatism (EULAR) recommends prophylaxis during the first months of urate-lowering therapy 2
Special Considerations
Renal Impairment
- Both medications require dose adjustments in patients with renal impairment
- For allopurinol: Start at lower doses (100 mg daily or less) with careful titration 1
- For colchicine: Dose adjustment or alternative prophylaxis may be needed 5
Drug Interactions
- About 26% of patients prescribed colchicine prophylaxis with allopurinol are also taking potentially interacting medications, most commonly statins (21%) 6
- Monitor for potential drug interactions, especially with strong CYP3A4 inhibitors which can increase colchicine toxicity 5
Common Side Effects
- Colchicine: Diarrhea (43% vs 4% with placebo), nausea, abdominal pain 3
- Allopurinol: Rash, gastrointestinal disturbances 7
Long-term Benefits
Long-term combination therapy with appropriate prophylaxis has been shown to:
- Reduce frequency and severity of acute gout flares 4
- Potentially preserve renal function (allopurinol may retard decline in renal function) 8
- Effectively reduce serum urate levels 7
Monitoring
- Monitor serum uric acid levels every 2-4 weeks during titration, then every 6 months once stable 2
- Assess renal function regularly, especially in patients with pre-existing renal disease 1
- Watch for signs of colchicine toxicity (severe diarrhea, vomiting, abdominal pain, muscle weakness)
The combination of allopurinol and colchicine represents standard of care when initiating urate-lowering therapy for gout, with the goal of effectively lowering serum urate while minimizing the risk of acute flares during the initial treatment period.