Fluoroquinolones and Theophylline Toxicity: Norfloxacin

To the Editor.—  Many drugs, including the new broad-spectrum fluoroquinolone anti-infective agents, are known to interfere with theophylline metabolism by the hepatic cytochrome P450 system, causing toxic reactions to theophylline. Wijnands et al¹ reported increases in plasma theophylline concentrations during coadministration of enoxacin (110.9%) and to a lesser degree during coadministration of ciprofloxacin (22.8%) and pefloxacin (19.6%). Although two recent pharmacokinetic studies^2,3 suggest that a drug-drug interaction between norfloxacin and theophylline also exists, we are not aware of any case reports of elevated theophylline levels associated with this drug in the medical literature.Three cases have been reported to the Food and Drug Administration that suggest theophylline toxic effects in patients taking norfloxacin. Each patient had a baseline steady-state theophylline level that was increased by at least 50% after starting norfloxacin therapy. A judgment was made that concomitant drugs or diseases were not likely to be responsible. All