title: QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine.
abstract: OBJECTIVE
  To report QTc interval prolongation associated with combination therapy including levofloxacin, imipramine, and fluoxetine.
  
  
  METHODS
  A 49-year-old white female presented to the emergency department with fever, aches, and pains for the past 3 days. She was diagnosed and treated for pyelonephritis in the hospital. Therapy included intravenous levofloxacin 500 mg every 24 hours and ceftriaxone 2 g every 24 hours, along with her medications upon admission, including imipramine 50 mg at bedtime and fluoxetine 10 mg/day. She was discharged after 5 days and returned the next day with chest tightness and shortness of breath. Upon the second admission, a 12-lead electrocardiogram showed a QTc interval of 509 msec. Levofloxacin was discontinued and the QTc interval fell to 403 msec. The patient was discharged 3 days later and instructed to consult with her primary care physician about discontinuing imipramine.
  
  
  CONCLUSIONS
  This adverse drug reaction is thought to be a pharmacodynamic additive effect among fluoxetine, imipramine, and levofloxacin. Fluoxetine is a potent inhibitor of CYP2D6, and imipramine is metabolized by CYP2D6. Therefore, fluoxetine is able to increase the plasma concentrations of imipramine, leading to QT interval prolongation. Taken with imipramine, levofloxacin can lead to even greater prolongation of the QT interval. Based on the Naranjo probability scale, levofloxacin was possibly associated with cardiac arrhythmias in our patient.
  
  
  CONCLUSIONS
  The use of levofloxacin alone, or more often in concomitant therapy with other medications that are known to prolong the QT interval, may cause QT interval prolongation; however, additional studies/case reports are needed to validate this conclusion.
authors.affiliation: Department of Clinical and Administrative Sciences, Mercer School of Pharmacy, 3001 Mercer University Drive, Atlanta, GA 30341-4155, USA. Nykamp_D@Mercer.edu
authors.forename: Diane L
authors.initials: DL
authors.lastname: Nykamp
authors.forename: Casey L
authors.initials: CL
authors.lastname: Blackmon
authors.forename: Paul E
authors.initials: PE
authors.lastname: Schmidt
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Roberson
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004357:Drug Synergism; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects*; D006801:Humans; D007099:Imipramine / Q000009:adverse effects*; D064704:Levofloxacin; D008133:Long QT Syndrome / Q000139:chemically induced*; D008875:Middle Aged; D015242:Ofloxacin / Q000009:adverse effects*
chemical_list: D000892:Anti-Infective Agents, Urinary; D000928:Antidepressive Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005473:Fluoxetine; D064704:Levofloxacin; D015242:Ofloxacin; D007099:Imipramine