The cardiotoxicity of macrolides: a systematic review

We aimed to evaluate the cardiac safety of macrolides either used alone or co-administered with other agents.

Pubmed and Embase databases were searched for the cardiac safety of macrolides in the treatment of infected patients. Identified studies were evaluated by two independent reviewers. Case reports, case series, controlled trials and randomly controlled trials were included.

A total of 48 reports (18 clinical studies and 30 case reports) were included in the present study. Among these reports, 25 were about macrolides used alone, and 23 about combination therapy. Based on the available data, we found that erythromycin carries the greatest risk of QT prolongation and Tdp from all macrolides in clinical practice (21/48), followed by clarithromycin (12/48) and azithromycin (6/48). Old age, high dosage, rapid administration and cardiac related diseases are additional risk factors.

Macrolides may induce cardiotoxicity themselves when used alone. When co-administered, they may also increase the risk of other drugs that potentially prolong the QTc interval or induce Tdp. Therefore, early and correct adjustment of the dosage, close daily ECG monitoring and the avoidance of co-administration of other known QT-prolonging agents should be used in order to prevent the development of adverse effects.