Late Breaking Original Research
Tuesday, November 14, 2023
08:30 AM–10:00 AM
Abstract
Introduction:
Colchicine reduces the risk of recurrent ischemic events in coronary heart disease. Colchicine drug-drug interactions (DDI) may increase the risk of gastrointestinal (GI) adverse effects, but the only available data include pharmacokinetic studies and case reports.
Research Question or Hypothesis:
Is there an association between concomitant CYP3A4 and P-gp-mediated DDIs and the risk of GI adverse events among people taking colchicine?
Study Design:
This study was a quantitative, post-hoc analysis of a randomized clinical trial.
Methods:
In this study, we re-analyzed data from the COLCORONA trial, which compared colchicine 0.5 mg twice daily for three days, then 0.5 mg daily after that (n=2235), and placebo (n=2253) for 30 days. The primary outcomes were GI adverse events with concomitant CYP3A4 Inhibitors and P-glycoprotein inhibitors. Data were analyzed using Stata 17.0, Wilcoxon rank-sum used for continuous variables, and Chi-square test for categorical variables. The association between the number of CYP3A4 or P-gp inhibitors used at baseline and the risk of overall and treatment-related GI adverse events was assessed separately in the colchicine and placebo arms using age-, sex- and eGFR-adjusted logistic regression models.
Results:
The median age was 54 years, and 54 % of participants were women. The most common DDIs were atorvastatin (14%), azithromycin (5%), and simvastatin (2%). The odds of an overall GI adverse event were 1.58 times higher for each additional CYP3A4 or P-gp inhibitor used at baseline in the colchicine arm (OR [95% CI]: 1.58 [1.05-2.38]), but not the placebo arm (OR [95% CI]: 0.91 [0.65-1.26]). Each additional CYP3A4 or P-gp inhibitor used at baseline was associated with a trend towards higher odds of treatment-related GI adverse events in the colchicine arm (OR [95% CI]: 1.48 [0.95-2.24]), but not the placebo arm (OR [95% CI]: 0.82 [0.59-1.14]).
Conclusion:
CYP3A4 and P-gp inhibitor DDIs may have a higher risk of colchicine-related GI adverse effects.
Presenting Author
Lama Alfehaid PharmD, MMECollege of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Authors
Omar Alkhezi PharmD
College of Pharmacy, Qassim University
Leo Buckley PharmD
Brigham and Women's Hospital
Peter Libby MD
Brigham and Women's Hospital
Akshay Desai MD, MPH
Cardiovascular Innovation Program at Brigham and Women's Hospital
Yahya Tawifk PharmD
Brigham and Women's Hospital
Amil Shah MD MPH
UT Southwestern Medical Center