Colchicine is Contraindicated with Verapamil
Colchicine must not be used in patients taking verapamil due to a life-threatening drug interaction that can cause severe toxicity, multiorgan failure, and death. 1
Mechanism of the Interaction
Verapamil is a moderate CYP3A4 inhibitor and P-glycoprotein inhibitor, both of which are the primary pathways for colchicine metabolism and elimination. 1 When verapamil blocks these pathways, colchicine accumulates to toxic plasma concentrations—increasing colchicine levels by 93-103% according to pharmacokinetic studies. 2, 3
This interaction is explicitly listed in the 2015 ACC/AHA/HRS guidelines as a specific precaution and drug interaction for verapamil, where colchicine is named among the contraindicated or high-risk medications. 1
Clinical Consequences of the Interaction
The combination can precipitate:
- Severe rhabdomyolysis and myopathy 2, 4
- Pancytopenia and bone marrow suppression 4, 5
- Multiorgan failure 4, 1
- Cardiovascular collapse and cardiac arrhythmias 4, 1
- Acute renal failure 1, 4
- Death 1, 4
The EULAR guidelines for Familial Mediterranean Fever explicitly state that concomitant administration of colchicine with verapamil can lead to colchicine toxicity that "can be life threatening" with "no effective means to remove colchicine from the tissues and the blood." 1
What to Do Instead
For Acute Gout Treatment:
- Use oral corticosteroids (prednisone 0.5 mg/kg/day for 5-10 days, or prednisolone 30-35 mg/day for 3-5 days) as first-line therapy. 3
- Intra-articular corticosteroid injection for monoarticular or oligoarticular involvement of accessible large joints (e.g., triamcinolone acetonide 40 mg for knee, 20-30 mg for ankle). 3
- NSAIDs at full FDA-approved doses (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) until complete resolution—but use cautiously if cardiovascular disease, heart failure, or renal impairment is present. 3
For Gout Prophylaxis During Urate-Lowering Therapy:
- Low-dose NSAIDs with proton pump inhibitor as first-line alternative prophylaxis. 3
- Low-dose prednisone (<10 mg/day) as second-line prophylaxis option. 3
If Verapamil Can Be Safely Discontinued:
- Wait at least 14 days after stopping verapamil before initiating colchicine to allow complete clearance of the CYP3A4/P-glycoprotein inhibitor. 3, 4
- This approach is only feasible if verapamil can be safely stopped and an alternative calcium channel blocker (such as amlodipine, which does not inhibit CYP3A4) or another antihypertensive/antiarrhythmic can be substituted. 4
Common Pitfalls to Avoid
- Do not attempt dose reduction of colchicine as a "compromise"—even a single 0.6 mg dose carries unacceptable toxicity risk when verapamil is present. 3, 4
- Do not assume the interaction is only relevant for high-dose colchicine—the interaction affects all colchicine doses, including prophylactic dosing (0.6 mg once or twice daily). 2, 4
- Do not overlook this interaction in patients with renal impairment—the combination of verapamil plus any degree of renal dysfunction creates exponentially higher risk of fatal colchicine toxicity. 1, 3, 6
- Do not attribute muscle symptoms solely to statins if the patient is on both colchicine and verapamil—colchicine's independent myotoxic effects or synergistic toxicity may be the culprit. 3, 7, 8