Several important interactions of fluoroquinolones with other drugs have been reported in the literature. The absorption of all fluoroquinolones is almost entirely inhibited by concomitant administration of di- and trivalent cations, such as aluminum and magnesium contained in antacids. The inhibition of absorption can be significant and can potentially lead to the failure of treatment, even when fluoroquinolone doses are separated from antacid doses by hours. Certain isozymes of the cytochrome P-450 system are selectively inhibited by some fluoroquinolones. The metabolism of theophylline and caffeine is inhibited by enoxacin and ciprofloxacin such that the dosage of theophylline may need to be reduced in order to avoid toxicity. In contrast, ofloxacin and norfloxacin cause less inhibition of the metabolism of these compounds, and reduction of the theophylline dosage is not routinely required. Evidence regarding the effect of fluoroquinolones on the disposition of other drugs known to be metabolized, such as warfarin and cyclosporine, is inconclusive. In summary, the safe and effective use of fluoroquinolone antibiotics requires careful consideration of concomitant drug therapy.

The effect of dose or dose interval on the pharmacodynamics of simulated high-dose intravenous ciprofloxacin therapy on infection due to Pseudomonas aeruginosa and Staphylococcus aureus was studied in an in vitro hollow-fiber model of infection. Simulated doses of 1,200 mg of ciprofloxacin per day as either 400 mg every 8 h or 600 mg every 12 h against P. aeruginosa resulted in selection of ciprofloxacin-resistant bacteria. The results with one test strain that was isolated from a patient prior to administration of intravenous ciprofloxacin demonstrated selection of a gyrA mutant in the model, as had occurred in vivo. A single 1,200-mg dose every 24 h did not select for bacterial resistance; however, breakthrough regrowth of ciprofloxacin-susceptible bacteria occurred. Dosages of 400 or 600 mg of ciprofloxacin every 12 h effectively reduced bacterial counts of one strain each of methicillin-susceptible or -resistant S. aureus, with no bacterial resistance detected at the end of experiment; in contrast, 200 mg every 12 h resulted in bacterial regrowth due to the selection of drug-resistant bacteria. These data show the need for high-dose intravenous ciprofloxacin, particularly with regimens producing high peak levels, for treatment of infections where selection for bacterial resistance is a clinical problem.