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When should colchicine be avoided?
- • Concurrent use of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors in the setting of renal or hepatic impairment.
Colchicine dose adjustments
Dose Adjustment for Acute Gout Flare | Dose Adjustment for Gout Prophylaxis | |
|---|---|---|
| Strong CYP3A4 inhibitors a | 0.6 mg × 1 dose, 0.3 mg 1 hour later Do not repeat in <3 days | 0.3 mg QOD, can increase to 0.3 mg QD with monitoring |
| Moderate CYP3A4 inhibitors b | 1.2 mg × 1 dose Do not repeat in <3 days | 0.3 mg QD, can increase to 0.6 mg QD with monitoring |
| Weak CYP3AR inhibitor c | No dose adjustment required | No dose adjustment required |
| P-gp inhibitors d | 0.6 mg × 1 dose Do not repeat in <3 days | 0.3 mg QOD, can increase to 0.3 mg QD with monitoring |
| Severe renal impairment (CrCl <30 mL/minute) | 1.2 mg × 1 dose, 0.6 mg 1 hour later Do not repeat more than once per 2 weeks | 0.3 mg QD |
| Dialysis | 0.6 mg × 1 dose Do not repeat more than once per 2 weeks | 0.3 mg twice a week, monitor closel |
- Note:Clarithromycin and erythromycin are inhibitors of both CYP3A4 and P-gp.Cyclosporine use is especially problematic due to scheduled, chronic dosing and common use in patients with solid organ transplant (a population at risk for gout). Colchicine should be avoided if possible (elevated risk of neuromyopathy reported).CrCl, Creatinine clearance; QD, every day; QOD, every other day.a Clarithromycin, erythromycin, ketoconazole, ritonavir. b Diltiazem, verapamil. c Azithromycin. d Cyclosporine, sunitinib, clarithromycin, erythromycin, tacrolimus (weaker P-gp inhibitor than cyclosporine) carvedilol.
- • Patients with concurrent renal and hepatic disease.
- • Patients with severe hepatic disease.
- • Pregnant women.
Colchicine is in the pregnancy risk category C, with suggestion of harm in animal but not human studies. Although its use in women of childbearing age would be rare for the indication of gout (outside of advanced renal disease), caution should be exercised in young women on this medication for FMF, Behćet’s disease, and other indications.
In high-risk patients with limited treatment options, how can colchicine be adjusted to mitigate risk?
Avoidance is the safest route; no antidotes exist to treat overdose; hemodialysis is ineffective.
