Quinolone Market Widens Further
Primary among the safety concerns for gatifloxacin and moxifloxacin, the two newest quinolones on the U.S. market, is their ability or potential to prolong the QT interval of the electrocardiogram. Under certain circumstances, this prolongation can lead to a ventricular arrhythmia.
In letters to Bristol-Myers Squibb and Bayer Corp., FDA outlined the studies to be conducted this year on Tequin's and Avelox's effects on the QT interval, particularly when these quinolones are at their highest concentration in the serum. Labeling for these newly approved quinolones warns health care practitioners that Tequin, or gatifloxacin, has the potential to prolong the QT interval and that Avelox, or moxifloxacin, has already been shown to do so. Further, FDA urges health care practitioners to use caution when having a patient take either of these quinolones along with another drug known to prolong the QT interval.
While moxifloxacin bears a stronger warning about cardiac effects than gatifloxacin, FDA requested in its letter to Bristol-Myers Squibb that the company look at possible changes in the QT interval resulting from pharmacodynamic interactions between its drug and certain types of antiarrhythmic drugs. FDA's concern about these quinolones' effects on the heart follows Glaxo Wellcome's removal of grepafloxacin, or Raxar, from the market last October.
Bacterial resistance to antimicrobials also enters into the decision of which quinolones to have on the formulary. On Feb. 2, levofloxacin became the first quinolone to receive FDA's stamp of approval for treating community-acquired pneumonia caused by Streptococcus pneumoniae strains resistant to penicillin. As part of the approval, Ortho-McNeil Pharmaceutical must send FDA an annual report from an active surveillance study of drug resistance among Streptococcus pneumoniae isolates.
With competition heating up, more quinolone manufacturers may pursue this point of distinctiveness and even advertise it before FDA approves. FDA reprimanded Bayer for its December press release suggesting moxifloxacin as effective against resistant pathogens. The agency had explicitly stated in a separate letter to Bayer that the agency would approve the expanded indication once the company submits data confirming the safety of moxifloxacin when in widespread use.
Further studies into the safety of gatifloxacin and moxifloxacin ignore a large population of potential patientschildren. FDA waived, not deferred, the federal requirement for Bristol-Myers Squibb and Bayer to assess the safety and effectiveness of gatifloxacin and moxifloxacin in pediatric patients. In the case of levofloxacin, FDA requested the manufacturer to submit plans for studying the drug's new use in children or request a waiver of this requirement.