title: Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.|Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Niedrig
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.|drugsafety.ch, Seestrasse 221, 8700, Küsnacht, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maechler
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Liesa
authors.initials: L
authors.lastname: Hoppe
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Natascia
authors.initials: N
authors.lastname: Corti
authors.affiliation: Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland. russmann@drugsafety.ch.|Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland. russmann@drugsafety.ch.|drugsafety.ch, Seestrasse 221, 8700, Küsnacht, Switzerland. russmann@drugsafety.ch.|Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland. russmann@drugsafety.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Russmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069059:Atorvastatin / Q000009:adverse effects / Q000627:therapeutic use; D003000:Clonidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D018942:Macrolides / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008508:Medication Errors; D008875:Middle Aged; D015363:Quinolones / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use; D062606:Tertiary Care Centers; D016171:Torsades de Pointes / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D015363:Quinolones; C023754:tizanidine; D000069059:Atorvastatin; D019821:Simvastatin; D003000:Clonidine
keywords: Drug interactions; Drug safety; ECG monitoring; Macrolide and quinolone antibiotics; Pharmacoepidemiology; Torsade de pointes (TdP)