Colchicine and Warfarin Interaction
There is no clinically significant pharmacokinetic or pharmacodynamic interaction between colchicine and warfarin that requires dose adjustment or additional INR monitoring beyond standard care. 1
Evidence Base
The most recent and highest quality evidence comes from a 2025 randomized controlled trial substudy of the LoDoCo2 trial, which specifically examined this interaction in 73 patients with chronic coronary disease using both low-dose colchicine (0.5 mg daily) and vitamin K antagonists 1:
- No significant change in INR when starting colchicine (mean INR 2.60 before vs. 2.67 during treatment, difference 0.07,95% CI -0.13 to 0.26; p=0.50) 1
- No significant change in INR when stopping colchicine (mean INR 2.70 during vs. 2.81 after stopping, difference 0.11,95% CI -0.12 to 0.33; p=0.34) 1
- No change in warfarin dosing requirements either when starting or stopping colchicine 1
- Time in therapeutic range (TTR) remained stable or slightly improved (65.8% before vs. 73.4% after, p=0.05) 1
Mechanism Considerations
While colchicine is a substrate for CYP3A4 and P-glycoprotein, and drug interactions with CYP3A4/P-gp inhibitors can cause serious toxicity including pancytopenia and multiorgan failure 2, warfarin does not inhibit these pathways. Warfarin is primarily metabolized by CYP2C9 (S-isomer) and CYP3A4 (R-isomer) but does not significantly inhibit CYP3A4 or P-gp 3.
Clinical Management
No additional INR monitoring beyond standard care is required when initiating or discontinuing colchicine in patients taking warfarin 1:
- Continue routine INR monitoring per standard anticoagulation protocols
- No prophylactic warfarin dose adjustment is necessary
- Standard colchicine dosing (0.5 mg daily for cardiovascular indications) can be used safely
Important Caveats
Do not confuse this with documented warfarin interactions that genuinely increase bleeding risk and require close monitoring 3, 4:
- NSAIDs (including COX-2 inhibitors) double bleeding risk and should be avoided 3, 5, 4
- Antiplatelet agents increase bleeding risk 1.74-fold 4
- SSRIs more than double bleeding risk 3, 4
- Acetaminophen >2g/day significantly increases INR by day 3 3, 5
- Antibiotics (particularly azoles, macrolides, quinolones) significantly increase INR 3, 6
Colchicine's own drug interactions occur with CYP3A4/P-gp inhibitors (such as clarithromycin, ketoconazole, ritonavir), not with warfarin 2. These combinations can cause life-threatening colchicine toxicity and require dose reduction or avoidance of colchicine.