A secondary analysis of the COLCORONA trial, involving 4,432 ambulatory patients with COVID-19, indicates that common drug-drug interactions do not significantly impact the clinical tolerability of colchicine. The study, published in JAMA Network Open, found that interactions with medications like statins and calcium channel blockers did not increase the risk of adverse events or affect colchicine's efficacy in preventing COVID-19-related hospitalization or death.
The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted across multiple countries between March 2020 and January 2021. Participants received either colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily) or a placebo for 27 days. The secondary analysis aimed to evaluate whether pre-existing drug-drug interactions influenced colchicine's safety and efficacy.
Impact of Drug Interactions on Adverse Events
The analysis identified baseline medications with known interactions with colchicine. The primary outcome was a composite of gastrointestinal adverse events. Results showed that while gastrointestinal adverse events were more frequent in the colchicine arm, the presence of drug-drug interactions did not significantly modify this effect. Specifically, the odds of any gastrointestinal adverse event were 1.80 times higher in the colchicine arm compared to placebo among those without drug-drug interactions, and 1.68 times higher among those with interactions (P=0.69 for interaction).
Effect on COVID-19 Outcomes
The study also examined the composite outcome of COVID-19 hospitalization or death. Drug-drug interaction status did not significantly alter colchicine's effect on this outcome (odds ratio, 0.91 for drug-drug interaction and 0.84 for no drug-drug interaction; P=0.80 for interaction).
Implications for Clinical Practice
"In this post hoc analysis of the randomized, double-blind, placebo-controlled COLCORONA trial, the presence of a drug-drug interaction leading to higher colchicine exposure at baseline was not associated with an increase in the risk of overall or gastrointestinal adverse events in the colchicine arm," the authors wrote. They noted that most drug-drug interactions were classified as ORCA class 3 or 4, indicating conditional use or minimal risk.
The most common interacting medications were rosuvastatin (12%) and atorvastatin (10%). The researchers suggest that the modestly increased colchicine exposure with concomitant atorvastatin use has little clinical relevance. These findings align with previous trials demonstrating the tolerability of colchicine and rosuvastatin in COVID-19.
Study Limitations
The authors acknowledged several limitations, including the focus on medications used at baseline and the exclusion of individuals at highest risk for adverse events. Rare adverse events, such as rhabdomyolysis, were not captured due to their delayed onset. Additionally, all participants had confirmed SARS-CoV-2 infection, which may have influenced their susceptibility to adverse reactions.
Conclusion
Despite these limitations, the study suggests that low-dose colchicine can be safely used in carefully selected patients with certain drug-drug interactions, provided they receive close monitoring. According to the researchers, these data may alleviate concerns over the safety of colchicine in patients receiving an interacting drug.
