Colchicine
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Dosing and administration[2]
Oral, with or without food. Two roles in gout: acute flare treatment (short course) and low-dose flare prophylaxis when initiating urate-lowering therapy. Not an analgesic; narrow therapeutic index with potential for fatal overdose.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Acute gout flare | 1.2 mg (two 0.6 mg tablets) at the first sign of a flare, then 0.6 mg one hour later (1.8 mg total over one hour). | Do not repeat a treatment course within 3 days. Most effective when started early in the flare. |
| Flare prophylaxis (starting urate-lowering therapy) | 0.6 mg once or twice daily; maximum 1.2 mg/day. Continue for at least the first 6 months of urate-lowering therapy. |
Renal adjustment. Mild to moderate impairment (creatinine clearance 30 to 80 mL/min): no dose change but monitor closely. Severe impairment (below 30 mL/min): start 0.3 mg/day and titrate cautiously. Dialysis: 0.3 mg twice weekly.
Hepatic. Caution and dose reduction in hepatic impairment; contraindicated in severe hepatic impairment combined with a strong CYP3A4 or P-gp inhibitor.
Monitoring
- Monitor for gastrointestinal toxicity (dose-limiting), and for neuromyopathy and myelosuppression, particularly with renal or hepatic impairment, in older patients, and with interacting drugs.
Contraindications
- Concomitant strong CYP3A4 or P-gp inhibitor in a patient with renal or hepatic impairment (risk of fatal toxicity).
- Combined severe renal and hepatic impairment.
Key interactions
- Strong and moderate CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir, diltiazem, verapamil, grapefruit juice) and P-gp inhibitors (cyclosporine): raise colchicine levels; reduce dose or avoid.
- Statins and fibrates: increased risk of myopathy and rhabdomyolysis.
- Digoxin: increased myopathy risk.
Clinical notes
How it is used in gout
One of the three first-line flare therapies (with NSAIDs and glucocorticoids), and a preferred prophylactic agent during ULT initiation. Low-dose is strongly recommended over high-dose given similar efficacy and fewer adverse effects.[1]
Monitoring
Primarily clinical monitoring for efficacy and toxicity. Dose adjustment in renal or hepatic impairment and with CYP3A4 or P-glycoprotein inhibitors is essential (monograph).[1]
Common effects
Background clinical knowledge: dose-dependent gastrointestinal effects (diarrhoea, nausea, abdominal cramps) are the most common and are dose-limiting.
Important cautions
Background and monograph, not the gout guideline: colchicine has a narrow therapeutic index; serious and fatal toxicity can occur with strong CYP3A4 inhibitors and P-glycoprotein inhibitors (for example clarithromycin, certain antifungals, ciclosporin), especially in renal or hepatic impairment. Neuromyotoxicity can occur. Reconcile dosing and interactions with the product monograph.
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
- COLCHICINE (colchicine 0.6 mg tablets) Product Monograph. Health Canada authorized product monograph. https://pdf.hres.ca/dpd_pm/00034804.PDF