Colchicine Dosing with Allopurinol

When initiating allopurinol for gout, use colchicine 0.5-1 mg daily for prophylaxis during the first 6 months of urate-lowering therapy. 1

Standard Prophylactic Dosing

Start with colchicine 0.5 mg daily, which can be increased to 1 mg daily if tolerated and needed. 2, 3
The American College of Rheumatology strongly recommends concomitant anti-inflammatory prophylaxis when starting any urate-lowering therapy, with colchicine as a preferred agent. 1
EULAR guidelines similarly recommend colchicine 0.5-1 mg/day during the first 6 months of urate-lowering therapy. 1

Continue prophylaxis for 3-6 months rather than shorter durations (<3 months). 1
Extend prophylaxis beyond 6 months if the patient continues to experience flares or has not achieved serum urate target. 1, 2
Data from febuxostat trials showed that 6 months of prophylaxis provided greater benefit than 8 weeks, with no increase in adverse events. 1

Reduce the colchicine dose in patients with renal impairment. 1, 3
In severe renal impairment (CKD stage 4-5), avoid colchicine entirely or use with extreme caution at significantly reduced doses. 3
Monitor closely for neurotoxicity and muscular toxicity in patients with any degree of renal dysfunction. 1

Absolutely avoid co-prescription of colchicine with strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporine, clarithromycin, ketoconazole, ritonavir). 1, 3, 4
These combinations can cause life-threatening toxicity including pancytopenia, multiorgan failure, and cardiac arrhythmias. 4
The common recommendation to simply reduce colchicine dose when given with CYP3A4/P-gp inhibitors is inadequate and may still result in toxicity or therapeutic failure. 4

Patients on statin therapy require monitoring for potential neurotoxicity and muscular toxicity when receiving prophylactic colchicine. 1, 3
Colchicine can cause myotoxicity, and coadministration with other myotoxic drugs (statins, fibrates) increases the risk of myopathy and rhabdomyolysis. 4
Elderly patients and those with multiple comorbidities warrant closer monitoring due to higher risk of adverse effects. 5

In a placebo-controlled RCT, colchicine 0.6 mg twice daily reduced acute gout attacks significantly (33% vs 77% with placebo, NNT=2) when starting allopurinol. 2, 3
However, a recent 2023 non-inferiority trial found that placebo was NOT non-inferior to colchicine when using the "start-low go-slow" allopurinol approach, with mean gout flares/month of 0.61 with placebo vs 0.35 with colchicine (difference 0.25, p=0.92 for non-inferiority). 6
This most recent high-quality evidence confirms that colchicine prophylaxis remains necessary even with gradual allopurinol dose escalation. 6

If colchicine is contraindicated or not tolerated, use low-dose NSAIDs with gastro-protection (naproxen 250 mg twice daily). 1, 2
Low-dose prednisone/prednisolone (5-10 mg daily) is an alternative, particularly in patients with CKD stage 3 or higher where NSAIDs are contraindicated. 2, 3
Avoid NSAIDs in severe renal impairment (CKD stage 4-5). 2

Do not stop prophylaxis abruptly at 6 months without assessing whether the patient has achieved serum urate target (<0.36 mmol/L or <6 mg/dL) and is flare-free. 2
Do not start with colchicine doses higher than 1 mg daily, as this increases gastrointestinal side effects (particularly diarrhea, RR=8.38 compared to placebo) without additional benefit. 2, 7
Do not fail to adjust colchicine dose in renal impairment, as this leads to accumulation and toxicity. 3
Do not overlook drug interactions, particularly with macrolide antibiotics, azole antifungals, and calcineurin inhibitors. 3, 4