Colchicine Prophylaxis When Starting Allopurinol
Yes, you should prescribe daily colchicine prophylaxis for at least 3-6 months when initiating allopurinol, with ongoing evaluation and continuation as needed if gout flares persist beyond 6 months. 1
Recommended Prophylaxis Regimen
The standard approach is colchicine 0.5-1 mg daily for the first 6 months of urate-lowering therapy (ULT). 1 This recommendation is strongly supported by multiple international guidelines:
- The 2020 American College of Rheumatology (ACR) strongly recommends administering concomitant anti-inflammatory prophylaxis therapy when initiating ULT 1
- The 2016 EULAR guidelines recommend prophylaxis during the first 6 months of ULT, with colchicine 0.5-1 mg/day as the preferred agent 1
- The 2006 EULAR recommendations support prophylaxis with colchicine (0.5-1 mg daily) or NSAIDs during the first months of urate-lowering therapy 1
Duration: 3-6 Months Minimum
Continuing prophylaxis for 3-6 months is strongly recommended over shorter durations (<3 months), with ongoing evaluation and continued prophylaxis as needed if flares persist. 1 The evidence shows:
- Shorter durations are associated with flares upon cessation of prophylaxis 1
- After stopping colchicine at 6 months, gout flares rise significantly 2
- Patients with ongoing flares during the first 6 months who have not achieved serum urate target may require longer prophylaxis 3
Evidence Supporting This Practice
The efficacy of colchicine prophylaxis is well-established:
In a placebo-controlled RCT of 43 patients starting allopurinol, colchicine 0.6 mg twice daily reduced acute attacks significantly (7/21 vs 17/22 in placebo group), with a number needed to treat (NNT) of 2. 1 This means colchicine prevents one in two patients from experiencing an attack.
A more recent 2023 non-inferiority trial demonstrated that placebo was NOT non-inferior to colchicine, confirming that colchicine significantly reduces gout flares (0.35 vs 0.61 flares/month, mean difference 0.25). 2 This is the highest quality recent evidence supporting prophylaxis.
A 2004 RCT showed colchicine prophylaxis reduced total flares (0.52 vs 2.91, p=0.008), reduced flare severity, and reduced likelihood of recurrent flares over 6 months. 4
Dosing Considerations
Start with colchicine 0.5 mg daily, which can be increased to 1 mg daily if tolerated. 1
Critical dose adjustments:
- Reduce dose in patients with renal impairment 1
- In CKD stage 3, use low-dose colchicine or low-dose prednisone for prophylaxis 5
- Avoid colchicine entirely in patients receiving strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporin, clarithromycin) 1
Important Safety Considerations
Be aware of drug interactions and toxicity risks:
- 26% of patients starting allopurinol with colchicine prophylaxis are prescribed potentially interacting medications, most commonly statins (21%). 6
- Colchicine can cause diarrhea (RR=8.38 compared to placebo) 1
- Monitor for neurotoxicity and muscular toxicity, especially in patients with renal impairment or concurrent statin use 1
- Adverse events are more common in patients with more comorbidities and severe chronic kidney disease 6
Alternative Prophylaxis Options
If colchicine is contraindicated or not tolerated:
- Low-dose NSAIDs with gastro-protection can be considered 1
- Low-dose prednisone/prednisolone is an alternative, particularly in CKD stage 3 1, 5
- NSAIDs should be avoided in severe renal impairment 1
Who Benefits Most from Prophylaxis
Target prophylaxis particularly for patients who:
- Had a gout flare in the month before starting allopurinol (OR 2.65 for flare risk) 3
- Are starting allopurinol at 100 mg daily (OR 3.21 for flare risk) 3
- Have not yet achieved serum urate target <0.36 mmol/L (6 mg/dL) at 6 months (OR 2.85 for continued flares) 3
Common Pitfall to Avoid
Do not stop prophylaxis abruptly at 6 months without assessing whether the patient has achieved serum urate target and is flare-free. 1 After cessation, monitor for flare activity and continue anti-inflammatory treatment as needed if the patient continues to experience gout flares. 1