What is the mechanism of action of colchicine (Colchicine) for pericarditis prophylaxis?

From the Guidelines

Colchicine prevents and treats pericarditis by inhibiting microtubule assembly and disrupting inflammatory pathways, primarily working by binding to tubulin proteins and preventing their polymerization into microtubules, which disrupts neutrophil migration, adhesion, and chemotaxis to sites of inflammation in the pericardium, as supported by the most recent guidelines 1. The mechanism of action of colchicine in pericarditis prophylaxis involves:

• Inhibiting microtubule assembly, which disrupts neutrophil migration, adhesion, and chemotaxis to sites of inflammation in the pericardium
• Binding to tubulin proteins, preventing their polymerization into microtubules
• Inhibiting the NLRP3 inflammasome, reducing the production of pro-inflammatory cytokines like IL-1β that drive pericardial inflammation
• Decreasing the release of superoxide anions and other inflammatory mediators from activated neutrophils For pericarditis prophylaxis, colchicine is typically prescribed at 0.5-0.6 mg once or twice daily, with lower doses (0.5 mg daily) for patients under 70 kg or those with renal impairment, as recommended by the European Society of Cardiology guidelines 1. Treatment duration usually ranges from 3-6 months for a first episode and up to 12-24 months for recurrent pericarditis, with common side effects including gastrointestinal symptoms like diarrhea, nausea, and abdominal pain, and colchicine should be used cautiously in patients with renal or hepatic impairment and is contraindicated during pregnancy and in those with severe renal or hepatic disease, as noted in the guidelines 1. However, the most recent guidelines from the American Heart Association and American College of Cardiology 1 provide updated recommendations for the management of pericarditis in competitive athletes, which should be considered in clinical practice.

From the FDA Drug Label

The mechanism by which Colchicine Tablets, USP exert their beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β The mechanism of action of colchicine for pericarditis prophylaxis is not explicitly stated in the provided drug label. However, based on the information provided, colchicine's mechanism of action is thought to involve:

• Interference with the intracellular assembly of the inflammasome complex
• Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules
• Prevention of the activation, degranulation, and migration of neutrophils It is essential to note that the label discusses the mechanism of action in the context of Familial Mediterranean Fever (FMF), not pericarditis. Therefore, no direct conclusion can be drawn about the mechanism of action of colchicine for pericarditis prophylaxis from this label 2.

From the Research

Mechanism of Action of Colchicine for Pericarditis Prophylaxis

The mechanism of action of colchicine in preventing pericarditis is not fully understood, but it is thought to involve the inhibition of microtubule polymerization, which reduces inflammation and prevents the recurrence of pericarditis 3, 4.

Efficacy of Colchicine for Pericarditis Prophylaxis

• Colchicine has been shown to be effective in reducing the risk of pericarditis recurrence in patients with acute or recurrent pericarditis 3, 4, 5.
• A meta-analysis of five controlled clinical trials found that colchicine use was associated with a reduced risk of pericarditis during follow-up (RR=0.40,95% CI 0.30 to 0.54, p for effect <0.001) 4.
• Colchicine has also been shown to be effective in reducing symptoms and improving quality of life in patients with pericarditis 3, 5.

Safety of Colchicine for Pericarditis Prophylaxis

• Colchicine is generally well tolerated, with gastrointestinal intolerance being the most frequent side effect (mean incidence 8%) 4, 5.
• A meta-analysis of five controlled clinical trials found that colchicine use was not associated with a significant higher risk of adverse events compared with placebo (RR=1.22,95% CI 0.71 to 2.10, p for effect 0.48) 4.
• However, colchicine use was associated with a higher risk of drug withdrawals due to adverse events (RR=1.85,95% CI 1.04 to 3.29, p for effect 0.04) 4.

Comparison of Colchicine Monotherapy versus Combination Therapy

• A retrospective, observational cohort study found that colchicine monotherapy was not significantly different from NSAID monotherapy or combination therapy in preventing pericarditis recurrence in patients with heart failure with reduced ejection fraction and/or coronary artery disease 6.
• However, the study suggested that a prospective, randomized trial is needed to further elucidate the efficacy of colchicine monotherapy for the treatment of acute pericarditis in these patients 6.