Question 18

Could you comment on the safety of levofloxacin compared to other fluoroquinolones?

Many other fluoroquinolones have fallen by the wayside because of adverse events. In contrast, levofloxacin has an exceptional safety record. The most recent general “class precautions” mandated by the US Food and Drug Administration (FDA) for the fluoroquinolones include general side effects such as neuropathy, prolongation of QTc, tendon rupture, and increased neuro-effects in seizure prone patients, which have only been reported very rarely with levofloxacin. Several studies have addressed the QTc prolongation concerns (65). A double-blind, placebo-controlled study evaluating the effect of levofloxacin, moxifloxacin and ciprofloxacin on the QT/QTc interval in healthy adults (66). These studies demonstrated that, compared to placebo, there was no statistically significant change from baseline at 500 mg doses, variable change at 1,000 mg doses and a statistically significant change at 1,500 mg doses of levofloxacin. These changes were not associated with any serious adverse events. In the study comparing levofloxacin, ciprofloxacin and moxifloxacin at 1,000, 1,500 and 800 mg, respectively. Post-dose changes were small and were indistinguishable between levofloxacin and ciprofloxacin but changes with moxifloxacin were significantly greater. Current recommendations are that levofloxacin (and other quinolones in general) be avoided in patients with known prolongation of the QT interval as well as those with uncorrected hypokalemia and patients taking medications that are known to prolong the QT interval such as class 1A agents (quinidine, procainamide) or class III antiarrythmiaagents (amiodarone, sotolol).

One additional precaution in use of the quinolones is the potential for musculoskeletal inflammation, which in rare instances, has been associated with tendonitis and tendon rupture.This has occurred more frequently in the elderly and in patients taking steroids. Hence, quinolone therapy should be stopped in any patient who experiences pain, inflammation or rupture of a tendon.

Although there have been specific warnings related to moxifloxacin regarding the potential for causing fulminant liver failure, this is another concern for the quinolone class in general. Physicians are now cautioned against use of moxifloxacin in patients with liver disease and, since this is such a ubiquitous problem, it severely restricts the use of this agent. It is recommended that any quinolone therapy be stopped if signs of hepatic inflammation occur. In addition, in the United States, gatifloxacin was withdrawn from sale because of glycemic side effects such as both hypoglycemic and hyperglycemic issues.* In contrast, levofloxacin has maintained the cleanest side effect profile of any fluoroquinolone to date.

^* FDA issued a notice in September 2008 to determine that gatifloxacin (Tequin^(R)) tablets, injection, and oral suspension, were withdrawn from sale for reasons of safety or effectiveness (67).