Can colchicine be taken together with allopurinol?

Colchicine and Allopurinol Can Be Safely Taken Together

Yes, colchicine can be taken together with allopurinol, and this combination is actually recommended during the initiation of allopurinol therapy to prevent acute gout flares. 1, 2

Rationale for Combination Therapy

Allopurinol is a urate-lowering therapy (ULT) that works by inhibiting xanthine oxidase, thereby reducing serum uric acid levels. However, when starting allopurinol:

• Rapid reduction in serum uric acid can trigger acute gout flares due to mobilization of urate crystals from tissue deposits 2
• These flares can discourage patients from continuing necessary treatment
• Prophylactic therapy is essential during the initial phase of ULT

Recommended Protocol

Starting Allopurinol:

• Begin with a low dose (100 mg daily) 1, 2
• Increase by 100 mg increments every 2-4 weeks until target serum uric acid level (<6 mg/dL or 360 μmol/L) is achieved 1
• Maximum recommended dose: 800 mg daily 2

Colchicine Prophylaxis:

• Dosage: 0.5-1 mg daily 1
• Duration: Continue for first 6 months of ULT 1
• Timing: Start colchicine when initiating allopurinol 2

Evidence Supporting Combination Therapy

A randomized, double-blind, placebo-controlled trial demonstrated that colchicine prophylaxis during allopurinol initiation:

• Reduced total gout flares (0.52 vs 2.91, p=0.008)
• Decreased flare severity
• Was well-tolerated 3

Important Precautions

Dose Adjustments Required:

1. Renal Impairment:

   • Reduce colchicine dose in patients with renal impairment 1
   • Adjust allopurinol dosing based on creatinine clearance 2

2. Drug Interactions:

   • Avoid co-prescription of colchicine with strong P-glycoprotein and/or CYP3A4 inhibitors 1, 4
   • Monitor for potential neurotoxicity and/or muscular toxicity when colchicine is used with statins 1

3. Adverse Events to Monitor:

   • Diarrhoea (most common with colchicine, HR 2.22) 5
   • Myalgia (HR 2.64) 5
   • Bone marrow suppression (rare but serious, HR 3.29) 5

Alternative Prophylaxis Options

If colchicine is not tolerated or contraindicated:

• Low-dose NSAIDs can be used for prophylaxis (if not contraindicated) 1
• However, NSAIDs carry their own risks including angina (HR 1.60), acute kidney injury (HR 1.56), and peptic ulcer disease (HR 1.67) 5

Long-term Considerations

• Allopurinol should be continued long-term to maintain serum uric acid below target level 1
• Colchicine is typically discontinued after 6 months of ULT, when crystal burden has been reduced 1
• Regular monitoring of serum uric acid levels is recommended to ensure therapeutic targets are maintained 1

By following these guidelines, the combination of colchicine and allopurinol can effectively manage gout while minimizing the risk of flares during treatment initiation.