Can Colchicine and Allopurinol Be Used Together?
Yes, colchicine and allopurinol should be used together—this combination is the standard of care when initiating urate-lowering therapy for gout. 1, 2
Standard Protocol for Combined Use
When starting allopurinol, you must provide colchicine prophylaxis at 0.6 mg once or twice daily for at least 6 months to prevent acute gout flares triggered by urate mobilization. 1, 2 This recommendation is supported by high-quality randomized controlled trial evidence showing that colchicine prophylaxis reduces gout flares from 77% to 33% (p=0.008) during allopurinol initiation. 1, 3
Dosing Algorithm by Renal Function
Normal renal function (CrCl >80 mL/min):
- Colchicine: 0.6 mg once or twice daily 2
- Allopurinol: Start at 100 mg daily, titrate by 100 mg every 2-4 weeks to achieve serum urate <6 mg/dL 2, 4
Mild-to-moderate renal impairment (CrCl 30-80 mL/min):
- Colchicine: Reduce to 0.5 mg once daily 4
- Allopurinol: Start at 50-100 mg daily, titrate slowly every 2-5 weeks 4
Severe renal impairment (CrCl <30 mL/min):
- Colchicine is contraindicated—avoid entirely 1, 2, 4
- Allopurinol: Start at 50 mg daily with extreme caution 4
- Use alternative prophylaxis: low-dose prednisone (<10 mg/day) or low-dose NSAID with PPI 2
Critical Contraindications to Combined Therapy
Absolute contraindication: Do not give colchicine to any patient taking strong CYP3A4 or P-glycoprotein inhibitors, especially with any degree of renal or hepatic impairment. 1, 2 These inhibitors include:
The combination can cause fatal multiorgan toxicity, cardiovascular collapse, and death. 2
Duration of Prophylaxis
Continue colchicine prophylaxis for at least 6 months, or for 3 months after achieving target serum urate (<6 mg/dL) if no tophi are present. 2 If tophi are present, continue for 6 months after reaching target. 2 Major trials (FACT, APEX, CONFIRMS) demonstrated that discontinuing prophylaxis at 8 weeks caused a spike in acute attacks, with flare rates doubling from 20% to 40%. 1
Management During an Acute Flare
If a patient already taking allopurinol develops an acute gout flare, continue the allopurinol without interruption. 2, 5 A randomized controlled trial showed that continuing allopurinol during acute attacks does not prolong the flare (15.4 vs 13.4 days, p=0.5). 5
For the acute flare itself, use the low-dose colchicine regimen: 1.2 mg at first sign, followed by 0.6 mg one hour later, then 0.6 mg once or twice daily until resolution. 2 This must be started within 36 hours of symptom onset for efficacy. 2
Common Pitfalls to Avoid
Do not start allopurinol without colchicine prophylaxis—this dramatically increases flare risk during the first 6 months. 1, 3
Do not use high-dose colchicine regimens—the obsolete 0.5 mg every 2 hours protocol causes severe diarrhea in 77-100% of patients with no additional benefit. 2, 6
Do not attempt dose reduction of colchicine as a "compromise" in patients on CYP3A4/P-gp inhibitors—even a single 0.6 mg dose carries unacceptable toxicity risk. 2
Monitor for drug interactions with statins—while statins were not associated with increased adverse events in a large UK cohort study of 13,945 patients, heightened monitoring for neuromuscular toxicity is advised, especially in renal impairment. 7, 2
Long-Term Renal Protection
The combination of colchicine and allopurinol may provide renal protection. A controlled 2-year study showed that patients receiving colchicine alone experienced significant decline in glomerular filtration rate, while those receiving allopurinol maintained stable renal function. 8 This suggests the hyperuricemia of gout is deleterious to kidneys, and allopurinol's hypouricemic effect retards renal decline. 8