Label updates on fluoroquinolones and QT prolongation

HSA would like highlight the recent changes made to the labelling of fluoquinolones relating to the risk of QT interval prolongation. Fluoroquinolones are broad spectrum antibiotics that are used to treat a wide range of indications such as the treatment of infections of the urinary tract, respiratory tract, skin and soft tissue, bones and joints, and abdominal cavity. Fluoroquinolones licensed locally include ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, lomefloxacin, gatifloxacin and pefloxacin.

Review by the Committee for Medicinal Products for Human Use (CHMP) in EU

QT interval prolongation is a known potential adverse effect associated with the use of fluoroquinolones.2 The CHMP of the European Medicines Agency (EMA)1 recently performed a review of QT prolongation related to fluoroquinolones, taking into consideration data from in vivo studies, in vitro electrophysiological studies and post-marketing data. From this review, the CHMP concluded that fluoroquinolones may be stratified into three groups depending on their potential for inducing QT interval prolongation. This was based on the fact that fluoroquinolones with a greater potential for inducing QT interval prolongation could lead to torsades de pointes, especially in the presence of risk factors such as hypokalaemia, hypomagnesaemia, bradycardia, or congenital or acquired prolongation of the QT interval.

HSA's assessment and actions

HSA has reviewed this safety issue in the local context, taking into consideration the data reviewed by EU CHMP. To date, HSA has not received any reports of QT prolongation associated with use of the above mentioned fluoroquinolones. HSA is currently working with drug companies to update the package inserts of all oral and intravenous formulations of fluoroquinolones to strengthen the warnings regarding the potential of QT interval prolongation associated with its use. The level of warning required for each fluoroquinolone will vary according to its risk for inducing QT interval prolongation. A summary of labelling updates required for each risk category of fluoroquinolones is listed below.

Risk category of fluoroquinolones

A. Summary of labelling updates for fluoroquinolones with a potential for inducing QT interval prolongation - moxifloxacin

  • contraindications in patients with conditions predisposing them to QT interval prolongation
  • warnings and precautions regarding the prolongation of QT interval and QT-prolongation related clinical conditions
  • updated list of medicinal products which may interact with the fluoroquinolones and contribute to an additive effect on QT interval prolongation
  • where available, the frequency of occurrence of QT interval prolongation and QT interval prolongation related clinical conditions
  • recommendations for symptomatic treatment and ECG monitoring in the event of overdose

B. Summary of labelling updates for fluoroquinolones with a low potential for inducing QT interval prolongation – levofloxacin, ciprofloxacin, norfloxacin and ofloxacin

  • warnings and precautions when used in patients with conditions predisposing to QT interval prolongation
  • use with caution in patients on other drugs known to prolong QT intervals
  • include the following as adverse reactions : ventricular arrhythmia and torsades de pointes, ECG QT prolonged
  • recommendations for symptomatic treatment and ECG monitoring in the event of overdose

C. Summary of labelling updates for fluoroquinolones with a very low potential for inducing QT interval prolongation or for which there is insufficient information available – pefloxacin and lomefloxacin

  • warnings and precautions to highlight that QT interval prolongation has been associated with the fluoroquinolone class of antibiotics

HSA's advisory

Healthcare professionals are encouraged to take into consideration the potential of a fluoroquinolone to cause QT prolongation when selecting this choice of therapy for their patients, especially in patients with risk factors. Healthcare professionals are also encouraged to report any adverse reactions suspected to be associated with the use of fluoroquinolones to the Vigilance Branch of HSA.

References

  1. European Medicines Agency Monthly report from the PhVWP December 2010 meeting.
    http://www.ema.europa.eu/ema/index.jsp?curl=search.jsp&q=fluoroquinolones+and+QT+prolongation&btnG=Search&murl=&mid=
  2. The Merck Manuals.
    http://www.merckmanuals.com/professional/sec14/ch170/ch170f.html?qt=fluoroquinolones&alt=sh#sec14-ch170-ch170f-322i
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