Historically, colchicine has been used primarily in the management of gout; however, in 2023, the FDA approved Lodoco, a newly marketed colchicine product, for the management of cardiovascular disease.
Colchicine (Lodoco; Agepha Pharma) is a drug that has been used by humans since ancient times.1 In the US, it was first approved by the FDA in 1961.2 Historically, colchicine has been used primarily in the management of gout; however, in 2023, the FDA approved Lodoco, a newly marketed colchicine product, for the management of cardiovascular disease.
Colchicine possesses anti-inflammatory properties which are attributed to a broad range of activities.3 These properties contribute to its effectiveness in the management of gout and possibly in other pathologies that are associated with inflammatory processes.3 When used for relief of an acute gout flare, the general dosing recommendation for colchicine is 1.2 mg given orally at the first sign of flare followed by 0.6 mg 1 hour later.4 For prophylaxis of recurrent gout flares in adults and adolescents, the general recommended dose is 0.6 mg once or twice daily.4
In contrast, for the recently approved indication of reducing the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple cardiovascular disease risk factors, the recommended dose is 0.5 mg of colchicine orally once daily.5
Though not fully understood, colchicine’s efficacy in cardiovascular disease is attributed to its ability to prevent the activation, degranulation, and migration of neutrophils. It may also interfere with the intracellular assembly of the inflammasome complex in neutrophils and monocytes that mediates activation of interleukin-1β.5
The clinical efficacy of colchicine in the prevention of cardiovascular events was evaluated in the LoDoCo2 trial,1 described in LODOCO’s prescribing information and with results published in the New England Journal of Medicine. In this randomized, controlled, double-blind trial, a total of 5522 patients with chronic coronary disease were assigned to receive 0.5 mg of colchicine once daily or matching placebo with a median duration of follow-up of 29 months. The primary end point was a composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.6
The investigators reported that the primary end point occurred in 6.8% of the patients in the colchicine group and in 9.6% of the patients in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 4.2% of the patients in the colchicine group versus 5.7% of the patients in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; HR 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence of death from non-cardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; HR 1.51; 95% CI, 0.99 to 2.31). Although this latter finding was not statistically significant, the investigators noted that this was a potential concern. Overall, the investigators concluded that the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo.6
Zayda Habib, Fiona Lee, Ming Zhu Lee, and Rachel Wu are all PharmD candidates in the Arnold & Marie Schwartz College of Pharmacy and Health Sciences at Long Island University.
Joseph P. Nathan, PharmD, MS, is professor of pharmacy practice and director of academic affairs in the Arnold & Marie Schwartz College of Pharmacy and Health Sciences at Long Island University.
As for the safety of the long-term use of low-dose colchicine, available data suggest that in the absence of significant renal or hepatic impairment, serious adverse effects in patients taking low-dose colchicine are no more frequent than placebo.1 Clinicians are advised, however, to evaluate their patients on low-dose colchicine to ensure compliance, monitor the blood counts and renal function, and to permanently cease therapy if estimated glomerular filtration rate (eGFR) falls below 45 mL/min/1.73 m2 or cytopenia develops. Moreover, it is important to monitor renal function when introducing or altering the dose of drugs that may lower eGFR, including diuretics and angiotensin-converting enzyme inhibitors. 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.5
Colchicine is an old drug with a newly approved indication. Importantly, its recommended dose in the management of cardiovascular disease is different than that recommended for gout. When used, clinicians are advised to monitor patients for decreased renal function, blood dyscrasias, and for concurrent use of drugs that may increase systemic exposure to colchicine.
