Ofloxacin

Drug Interactions Antacids, Sucralfate, Metal Cations, Multivitamins Quinolones form chelates with alkaline earth and transition metal cations. Administration of quinolones with antacids containing calcium, magnesium, or aluminum, with sucralfate, with divalent or trivalent cations such as iron, or with multivitamins containing zinc or with didanosine, chewable/buffered tablets or the pediatric powder for oral solution may substantially interfere with the absorption of quinolones resulting in systemic levels considerably lower than desired.

These agents should not be taken within the two-hour period before or within the two-hour period after ofloxacin administration (see DOSAGE AND ADMINISTRATION ). Caffeine Interactions between ofloxacin and caffeine have not been detected. Cimetidine Cimetidine has demonstrated interference with the elimination of some quinolones. This interference has resulted in significant increases in half-life and AUC of some quinolones. The potential for interaction between ofloxacin and cimetidine has not been studied. Cyclosporine Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with some other quinolones.

The potential for interaction between ofloxacin and cyclosporine has not been studied. Drugs Metabolized by Cytochrome P450 Enzymes Most quinolone antimicrobial drugs inhibit cytochrome P450 enzyme activity. This may result in a prolonged half-life for some drugs that are also metabolized by this system (e.g., cyclosporine, theophylline/methylxanthines, warfarin) when coadministered with quinolones. The extent of this inhibition varies among different quinolones (see other Drug Interactions ).

Non Steroidal Anti-Inflammatory Drugs The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including ofloxacin, may increase the risk of CNS stimulation and convulsive seizures (see WARNINGS and PRECAUTIONS , General ). Probenecid The concomitant use of probenecid with certain other quinolones has been reported to affect renal tubular secretion. The effect of probenecid on the elimination of ofloxacin has not been studied. Theophylline Steady-state theophylline levels may increase when ofloxacin and theophylline are administered concurrently.

As with other quinolones, concomitant administration of ofloxacin may prolong the half-life of theophylline, elevate serum theophylline levels, and increase the risk of theophylline-related adverse reactions. Theophylline levels should be closely monitored and theophylline dosage adjustments made, if appropriate, when ofloxacin is coadministered. Adverse reactions (including seizures) may occur with or without an elevation in the serum theophylline level (see WARNINGS and PRECAUTIONS , General ). Warfarin Some quinolones have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives.

Therefore, if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives, the prothrombin time or other suitable coagulation test should be closely monitored. Antidiabetic Agents (e.g., Insulin, Glyburide/Glibenclamide) Since disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concurrently with quinolones and an antidiabetic agent, careful monitoring of blood glucose is recommended when these agents are used concomitantly (see PRECAUTIONS , General and Information for Patients ).

Pregnancy Teratogenic Effects Pregnancy Category C Ofloxacin has not been shown to have any teratogenic effects at oral doses as high as 810 mg/kg/day (11 times the recommended maximum human dose based on mg/m 2 or 50 times based on mg/kg) and 160 mg/kg/day (4 times the recommended maximum human dose based on mg/m 2 or 10 times based on mg/kg) when administered to pregnant rats and rabbits, respectively. Additional studies in rats with oral doses up to 360 mg/kg/day (5 times the recommended maximum human dose based on mg/m 2 or 23 times based on mg/kg) demonstrated no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the newborn.

Doses equivalent to 50 and 10 times the recommended maximum human dose of ofloxacin (based on mg/kg) were fetotoxic (i.e., decreased fetal body weight and increased fetal mortality) in rats and rabbits, respectively. Minor skeletal variations were reported in rats receiving doses of 810 mg/kg/day, which is more than 10 times higher than the recommended maximum human dose based on mg/m 2 . There are, however, no adequate and well-controlled studies in pregnant women. Ofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (see WARNINGS ).

Nursing Mothers In lactating females, a single oral 200 mg dose of ofloxacin resulted in concentrations of ofloxacin in milk that were similar to those found in plasma. Because of the potential for serious adverse reactions from ofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS and ADVERSE REACTIONS ).