Colchicine

Established anti-inflammatory with strong evidence for gout and cardiovascular event reduction (COLCOT, LoDoCo2 trials). Narrow therapeutic window requires careful dosing.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

COLCOT and LoDoCo2 trials demonstrated significant reduction in cardiovascular events in post-MI and chronic coronary disease patients. Mechanism involves microtubule disruption, NLRP3 inflammasome inhibition, and neutrophil chemotaxis reduction. FDA-approved for gout and FMF; cardiovascular use is expanding.

• Proven cardiovascular event reduction in major RCTs
• Established treatment for gout and FMF
• Potent anti-inflammatory via NLRP3 inhibition

Gout flare: 1.2 mg then 0.6 mg one hour later. Prophylaxis: 0.6 mg once or twice daily. Cardiovascular: 0.5 mg/day (LoDoCo2 dose).

• Diarrhea (dose-limiting)
• Nausea
• Abdominal pain
• Myelosuppression (overdose)

Narrow therapeutic index — overdose can be fatal. GI toxicity is dose-limiting. Severe interactions with CYP3A4 inhibitors and P-glycoprotein inhibitors. Contraindicated in severe renal or hepatic impairment.

Cardiovascular benefit is well-established but the longevity extension hypothesis requires more data.

• Pain60
• Longevity55
• Immunity45