Cardiovascular Toxicity Profile of Macrolides Investigated Using VigiBase Data: A Pharmacovigilance Study
Yuki Kono1,2, Takahiro Niimura3,4, Mitsuhiro Goda1,5
1Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
Abstract:
Macrolides are associated with cardiovascular toxicity risk. However, data on their cardiovascular toxicity profiles beyond QT prolongation are limited, and differences in the profiles among various macrolide antibiotics remain unclear. We investigated the cardiovascular toxicity profiles of different macrolides using VigiBase, a global database of individual case-safety reports. Disproportionality analysis was performed using VigiBase, the WHO Pharmacovigilance database, from 1968 to December 2023. Associations between five macrolides (erythromycin, clarithromycin, azithromycin, josamycin, and roxithromycin) and adverse events (20 cardiovascular toxicities and diarrhea as a positive control) were predicted using the reporting odds ratio. Reported outcomes were evaluated for suggested drug-adverse event associations. Among the 36,129,107 reports analyzed, azithromycin was the most commonly used macrolide, followed by erythromycin, clarithromycin, roxithromycin, and josamycin. Diarrhea was frequently reported among users. Azithromycin use was associated with hypertension, cardiac valve disorders, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, cardiac conduction disorders, heart failure, and hemorrhage-related laboratory abnormalities. Erythromycin and clarithromycin use were also associated with cardiac valve disorders, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, and cardiac conduction disorders. The rates of caused/prolonged hospitalization in azithromycin-related hypertension, heart failure, and bleeding-related laboratory abnormality were 46%, 45%, and 50%, respectively. Each of the macrolide antimicrobials was associated with various cardiovascular toxicities, including Cardiac valve disorder, shock, and QT prolongation. Notably, azithromycin was associated with an increased frequency of reported hypertension and heart failure, distinguishing it from the other drugs. These results highlight the importance of considering the cardiovascular toxicity profile of individual macrolide antibiotics when prescribing them.
Insights
Macrolide antibiotics like azithromycin carry cardiovascular risks beyond QT prolongation, including hypertension and heart failure. Understanding these varied toxicity profiles is crucial for safe prescribing.
Area of Science:
- Pharmacovigilance
- Cardiovascular Toxicology
- Antimicrobial Safety
Background:
- Macrolides are linked to cardiovascular toxicity, but detailed profiles beyond QT prolongation are limited.
- Differences in cardiovascular risk among macrolide antibiotics are not well-defined.
Purpose of the Study:
- To investigate and compare the cardiovascular toxicity profiles of five macrolide antibiotics.
- To identify specific adverse cardiovascular events associated with individual macrolides.
Main Methods:
- Utilized VigiBase, a global pharmacovigilance database (1968-2023).
- Performed disproportionality analysis using reporting odds ratio for five macrolides (azithromycin, erythromycin, clarithromycin, josamycin, roxithromycin) and 20 cardiovascular adverse events.
- Evaluated reported outcomes for drug-adverse event associations.
Main Results:
- Azithromycin use was associated with hypertension, cardiac valve disorders, arrhythmias, QT prolongation, conduction disorders, heart failure, and bleeding abnormalities.
- Erythromycin and clarithromycin showed associations with cardiac valve disorders, arrhythmias, QT prolongation, and conduction disorders.
- Azithromycin demonstrated a higher frequency of reported hypertension and heart failure compared to other macrolides, with significant hospitalization rates.
Conclusions:
- All macrolide antimicrobials carry cardiovascular risks, including cardiac valve disorders, shock, and QT prolongation.
- Azithromycin presents a distinct cardiovascular toxicity profile, notably linked to increased hypertension and heart failure.
- Clinicians should consider individual macrolide cardiovascular toxicity profiles during prescription to mitigate patient risk.
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