Polypharmacy and the QT interval

A mini-systematic review was carried out to examine the evidence base of the effect of multiple drug administration (polypharmacy) on the QT interval in healthy humans. Prolongation of the electrocardiograph QT interval may lead to fatal cardiac arrhythmias and this may be induced by multiple drug administration. Many medications prolong the QT interval and when one of these medications is co-administered with another drug that shares the same pharmacokinetic mechanisms, there is potential for a drug interaction to occur that may prolong the QT interval past normal limits. Four clinical trials were obtained that examined different drug combinations. The drug combinations used were clinically relevant and are frequently found both in community and hospital-based care. All the studies found increases in circulating drug levels when medications were administered concomitantly. This increase in drug plasma level resulted in QT prolongation in two studies. Thus, depending on the drug combinations used, concomitant dual medication therapies in healthy adults may increase the risk of QT prolongation. This highlights the potential risk of polypharmacy, particularly when patients are pharmacokinetically impaired, as may be the case in many chronic diseases and older age.