Clinical twisters: Assessing risk to QT interval

April 16, 2007

A 70-year-old woman, T.R., has been transferred from an extended care nursing facility to your hospital with symptoms of fever, dyspnea with respiratory difficulty, cough, and sputum production. Her current medications include methadone 200 mg/ day (pain syndrome), risperidone (Risperdal, Janssen) 2 mg twice daily, digoxin 0.125 mg daily, and furosemide 20 mg twice daily.

A 70-year-old woman, T.R., has been transferred from an extended care nursing facility to your hospital with symptoms of fever, dyspnea with respiratory difficulty, cough, and sputum production. Her current medications include methadone 200 mg/ day (pain syndrome), risperidone (Risperdal, Janssen) 2 mg twice daily, digoxin 0.125 mg daily, and furosemide 20 mg twice daily. T.R.'s chest X-ray shows a pulmonary infiltrate in the right middle and upper lobes of the right lung with lobar consolidation. She is diagnosed with pneumonia, and her physician prescribes moxifloxacin (Avelox, Bayer) 400 mg IV/24 hours. Your student calls this order to your attention; her journal club recently discussed the problem of QT prolongation and this regimen concerns her. What do you recommend?

The medications T.R. is already taking may indicate a significant underlying dysrhythmia. She is receiving a high dose of methadone, which according to the literature, can contribute to QT prolongation and torsades de pointes. She is taking digoxin and furosemide without potassium supplementation (T.R. could be hypokalemic), and she is elderly. Studies show individuals with underlying cardiac anomalies, advanced age, female sex, concurrent QT-prolonging agents, hypokalemia, or hypomagnesemia have an increased incidence of QT prolongation and torsades de pointes. These factors should be considered in antibiotic choice.

According to recent pneumonia guidelines, individuals presenting from long-term care facilities with pneumonia should receive a respiratory fluoroquinolone (levofloxacin, moxifloxacin) as inpatients. The QT prolongation potential associated with fluoroquinolones differs among individual agents: Sparfloxacin (Zagam, Mylan) and grepafloxacin (Raxar, Otsuka) show the greatest incidence; other agents, e.g., moxifloxacin and levofloxacin (Levoquin, Ortho-McNeil), show lesser incidence. These conclusions are drawn from multiple trials of more than 200 patients and adverse reporting through the FDA. We do not know how well T.R. is rate/rhythm controlled, so to err on the side of caution, it is best to proceed with the secondary guideline recommendation, a beta-lactam and an advanced macrolide.

Paul J. Setlak, Pharm.D. Pharmacy Practice Resident and Clinical Associate University of Illinois at Chicago College of Pharmacy

Independent risk factors for QTc prolongation include female gender, age 65 years or older, bradycardia, hypokalemia, a history of cardiac disease, and concomitant QT-prolonging drugs. T.R. presents with several of these risk factors in addition to the potential individual and/or synergistic effects of moxifloxacin, methadone, and risperidone. Fluoroquinolones have been associated with cardiac arrhythmias in trials and case reports. In fact, severe cardiac arrhythmias related to sparfloxacin and grepafloxacin led to these drugs being withdrawn from the market.

In a prospective, randomized, double-blind trial of 387 patients reviewing cardiac safety of moxifloxacin and levofloxacin, investigators found comparable cardiac rhythm safety profiles in high-risk elderly patients with community-acquired pneumonia (CAP). Mean QTc change for moxifloxacin after three days of treatment was determined to be +6.4 ms (+/- 23 ms). While the clinical significance of a single agent affecting cardiac rhythm may not require intervention, the combination of several risk factors may warrant additional investigation. T.R. should have a baseline EKG, electrolytes, and her cardiac history assessed before initiating a quinolone antibiotic. A sputum culture obtained prior to antibiotic therapy may be beneficial in isolating the causative pathogen and narrowing the antibiotic spectrum. Infectious Diseases Society of America guidelines for CAP would support use of ceftriaxone and azithromycin as a reasonable alternative to a fluoroquinolone alone. Since T.R. lives in an extended care nursing facility, multidrug resistance may also be a factor in empiric antimicrobial selection.

John D. Kanell, Pharm.D., BCPS Coordinator of Drug Information Services, Pharmacy Wilson N. Jones Medical Center Sherman, Texas