Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation.

ABSTRACT

PURPOSE: Some macrolide and quinolone antibiotics (MQABs) are associated with QT prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug interactions (DDIs). There is limited data on the frequency and management of such risks in clinical practice. We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions. METHODS: We conducted an observational study within our pharmacoepidemiological database derived from electronic medical records of a tertiary care hospital. Among all users of MQAB associated with TdP, we determined the prevalence of additional QT-prolonging drugs and risk factors and identified contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine. Electrocardiographic (ECG) monitoring and associated adverse events were validated in medical records. RESULTS: Among 3444 administered courses of clarithromycin, erythromycin, azithromycin, ciprofloxacin, levofloxacin, or moxifloxacin, there were 1332 (38.7 %) with concomitant use of additional QT-prolonging drugs. Among those, we identified seven cases of drug-related QT prolongation, but 49.1 % had no ECG monitoring. Of all MQAB users, 547 (15.9 %) had hypokalemia. Forty-four MQAB users had contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine and three of those related adverse drug reactions. CONCLUSION: In the studied real-life setting, we found a considerable number of MQAB users with additional risk factors for TdP but no ECG monitoring. However, adverse drug reactions were rarely found, and costs vs. benefits of ECG monitoring have to be weighted. In contrast, avoidable risk factors and selected contraindicated pharmacokinetic interactions are clear targets for implementation as automated alerts in electronic prescribing systems.