Colchicine

• Gout flare treatment and prevention
• Familial Mediterranean fever
• Pericarditis
• Cardiovascular disease secondary prevention (emerging)

Colchicine is an anti-inflammatory medication with a unique mechanism of action that has been used for centuries to treat gout. Beyond gout, modern clinical trials have established its role in cardiovascular disease prevention and treatment of other inflammatory conditions including familial Mediterranean fever and pericarditis.

Mechanism of Action

Colchicine works primarily by inhibiting microtubule polymerization through binding to tubulin. This disrupts multiple cellular functions including neutrophil migration, chemotaxis, and phagocytosis. By preventing microtubule formation, colchicine inhibits the assembly of the inflammasome, reducing the production of interleukin-1β (IL-1β), a key cytokine in the inflammatory response to urate crystals in gout.

The anti-inflammatory effects extend beyond the inflammasome. Colchicine reduces neutrophil adhesion to endothelium, decreases oxidative stress, and may have direct effects on atherosclerotic plaque stability, which explains its cardiovascular benefits beyond its effects on gout.

Available Formulations

Colchicine is available as oral tablets in 0.6 mg strength (Colcrys) and as oral capsules (Mitigare). An oral solution is available for patients who have difficulty swallowing tablets. The 0.6 mg dose replaced the older 0.5 mg formulation following FDA standardization. Generic formulations are available.

FDA-Approved Indications

Colchicine is FDA-approved for prophylaxis and treatment of gout flares in adults, treatment of familial Mediterranean fever (FMF) in adults and children 4 years and older, and treatment of acute and recurrent pericarditis in adults and children. The COLCOT trial has also established benefits for secondary cardiovascular prevention, though this is not yet an FDA-approved indication.

Dosing Guidelines

For acute gout flare: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg). For gout prophylaxis: 0.6 mg once or twice daily. For FMF: 1.2-2.4 mg daily in divided doses. For pericarditis: Loading dose followed by 0.5-1 mg daily depending on body weight and tolerability. Lower doses are required with renal or hepatic impairment and with certain drug interactions.

Cardiovascular Benefits

The COLCOT trial demonstrated that low-dose colchicine (0.5 mg daily) significantly reduced cardiovascular events in patients with recent myocardial infarction. The LODOCO2 trial showed similar benefits in patients with chronic coronary disease. These findings support the inflammatory hypothesis of atherosclerosis and have expanded the potential uses of colchicine.

Important Safety Considerations

Colchicine has a narrow therapeutic index, and toxicity can be fatal. Symptoms of toxicity include nausea, vomiting, diarrhea, abdominal pain, and may progress to multi-organ failure. The maximum recommended dose for gout flares should not be exceeded. Use is contraindicated in patients with both renal and hepatic impairment. Blood dyscrasias including aplastic anemia, agranulocytosis, and thrombocytopenia have been reported. Neuromyopathy can occur with long-term use.

Drug Interactions

Strong CYP3A4 inhibitors (clarithromycin, ketoconazole, HIV protease inhibitors) and P-glycoprotein inhibitors (cyclosporine) significantly increase colchicine levels and can lead to toxicity; dose reduction is mandatory and repeat dosing must be delayed. Statins and other myotoxic drugs may increase the risk of myopathy. Grapefruit juice should be avoided. Concurrent use with digoxin may increase digoxin levels.

Special Populations

Dose adjustments are required in renal impairment. In severe renal impairment, lower doses and extended intervals between courses are necessary. Colchicine is contraindicated in patients with both renal and hepatic impairment taking P-gp or strong CYP3A4 inhibitors. Use during pregnancy should weigh benefits against potential risks. Male patients should be aware that colchicine may affect sperm production and function.

Learn more at MedlinePlus