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

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Acknowledgments

The authors would like to thank Dr. Guido Bucklar and Michael Fetzer from the hospital’s Department of Medical Informatics for the data extraction from the clinical information system’s database and their support of our research.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland

    David Niedrig, Sarah Maechler, Liesa Hoppe, Natascia Corti & Stefan Russmann

  2. Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland

    David Niedrig & Stefan Russmann

  3. drugsafety.ch, Seestrasse 221, 8700, Küsnacht, Switzerland

    Sarah Maechler & Stefan Russmann

  4. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland

    Helen Kovari

  5. Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland

    Stefan Russmann

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  1. David Niedrig
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Correspondence to Stefan Russmann.

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The work presented in this manuscript was supported by unrestricted research grants to Stefan Russmann from the Swiss National Science Foundation (grant #320030_143867) and ID Suisse AG.

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All authors declare that they have no conflict of interest regarding the presented work.

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Niedrig, D., Maechler, S., Hoppe, L. et al. Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Eur J Clin Pharmacol 72, 859–867 (2016). https://doi.org/10.1007/s00228-016-2043-z

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