LODOCO

The evidence for the efficacy of colchicine in patients with cardiovascular events is derived from published literature (LoDoCo2) along with other supportive studies. The LoDoCo2 trial was an investigator-initiated, randomized, placebo controlled, double-blind, event-driven trial conducted to assess the efficacy of colchicine 0.5mg once daily orally in patients with stable coronary artery disease. The study included 5522 patients, in which 2762 were assigned to the colchicine group and 2760 to placebo. The baseline characteristics of the patients were balanced between the trial groups. Patient...

6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. In the LoDoCo2 trial, myalgia was reported for 21.2% of individuals randomized to colchicine and 18.5% of individuals randomized to matching placebo (...

Concurrent use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors with LODOCO is contraindicated, because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses [see Drug interactions (7)] . LODOCO use is contraindicated in patients with renal failure (Creatinine clearance less than 15 mL/minute) and severe hepatic impair...

5.1 Blood Dyscrasias LODOCO can cause myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia, which can be life-threatening or fatal [see Adverse Reactions (6)] . Gastrointestinal symptoms often are the first sign of colchicine toxicity, so new symptoms should prompt an evaluation for toxicity. Concomitant use of drugs that reduce the metabolism of colchicine or the presence of hepatic or renal impairment increases the risk of developing blood dyscras...

7. DRUG INTERACTIONS Colchicine is a substrate for the efflux transporter P-glycoprotein (P-gp). CYP3A4 is the primary enzyme involved in the metabolism of colchicine. If LODOCO is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely (Table 1).

Table 1Drug Interactions Drug class Outcome/effect Clinical comment Strong CYP...