Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial.

Publication date: Sep 03, 2024

Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0. 5 mg twice daily for 3 days, then 0. 5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1. 80 (95% CI, 1. 51-2. 15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1. 68 (95% CI, 1. 24-2. 26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction (Pā€‰=ā€‰. 69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0. 91; 95% CI, 0. 59-1. 40 for drug-drug interaction and 0. 84; 95% CI, 0. 60-1. 19 for no drug-drug interaction; Pā€‰=ā€‰. 80 for interaction). In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. ClinicalTrials. gov Identifier: NCT04322682.

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Concepts Keywords
Canada Aged
Clinicaltrials Betacoronavirus
Diabetes Colchicine
Greece Colchicine
Coronavirus Infections
COVID-19
COVID-19 Drug Treatment
Double-Blind Method
Drug Interactions
Female
Humans
Male
Middle Aged
Pandemics
Pneumonia, Viral
SARS-CoV-2

Semantics

Type Source Name
disease MESH Drug Interactions
drug DRUGBANK Colchicine
disease MESH COVID 19
disease MESH death
disease MESH infection
disease MESH heart failure
disease MESH myocardial infarction
drug DRUGBANK Rosuvastatin
drug DRUGBANK Atorvastatin
drug DRUGBANK Amlodipine
drug DRUGBANK Methylphenidate
disease IDO blood
disease MESH dyspnea
disease MESH pancytopenia
disease IDO history
disease MESH allergic reaction
disease MESH cirrhosis
disease MESH chronic active hepatitis
drug DRUGBANK Erythromycin
drug DRUGBANK Clarithromycin
drug DRUGBANK Ciclosporin
drug DRUGBANK Verapamil
disease MESH hypertension
drug DRUGBANK Didanosine
disease MESH Coronavirus Infections
disease MESH Pneumonia

Original Article

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