Norfloxacin: Drug Interactions
Antacids
Antacids containing magnesium hydroxide or aluminum hydroxide may decrease absorption of oral norfloxacin, and the drugs probably should not be administered concomitantly. Patients should be instructed not to ingest antacids concomitantly with or within 2 hours of a norfloxacin dose. The mechanism of this interaction has not been fully elucidated to date, but studies using ciprofloxacin indicate that antacids containing magnesium and aluminum ions may bind to, and form insoluble complexes with, quinolones in the GI tract.
Antifungal Agents
Norfloxacin is inactive against fungi when used alone, but results of some in vitro studies using Candida suggest that the drug may enhance the antifungal activity of antifungal agents (e.g., amphotericin B, flucytosine, ketoconazole, miconazole [systemic form no longer commercially available in the US], nystatin). There are conflicting reports on this interaction, however, and in at least one in vitro study norfloxacin had no effect on the antifungal activity of amphotericin B. Further study is needed to evaluate the antifungal effect when norfloxacin is used in conjunction with an antifungal agent.
Aminoglycosides
The antibacterial activities of norfloxacin and aminoglycosides may be additive or partially synergistic in vitro against gram-negative bacteria (e.g., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus). However, synergism between the drugs appears to be unpredictable, and indifference or antagonism has also been reported when norfloxacin was used in conjunction with an aminoglycoside against Enterobacteriaceae or Ps. aeruginosa.
Coumarin Anticoagulants
Initiation of oral norfloxacin therapy in patients stabilized on warfarin has resulted in prolongation of the prothrombin time in several patients and, in at least one patient, concomitant use of the drugs resulted in an increased prothrombin time and fatal pontine hemorrhage. The mechanism of this interaction has not been determined to date, but norfloxacin may displace the anticoagulants from serum albumin binding sites. Norfloxacin should be administered with caution in patients receiving a coumarin anticoagulant and prothrombin time or another appropriate coagulation test should be closely monitored.
Cyclosporine
Concomitant use of cyclosporine and norfloxacin has resulted in increased serum concentrations of cyclosporine. Therefore, the manufacturer recommends that cyclosporine serum concentrations be monitored and appropriate dosage adjustments made in patients receiving the drug concomitantly with norfloxacin.
Didanosine
Didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or pediatric powder for oral solution prepared as an admixture with antacid may interfere with oral absorption of norfloxacin. To minimize the possibility of interaction, patients should be instructed not to ingest didanosine preparations concomitantly with or within 2 hours of a norfloxacin dose.
Iron, Multivitamins, and Mineral Supplements
Oral multivitamin and mineral supplements containing divalent or trivalent cations such as iron or zinc may interfere with oral absorption of norfloxacin resulting in decreased serum and urine concentrations of the quinolone. Therefore, these multivitamins and/or mineral supplements should not be ingested concomitantly with or within 2 hours of a norfloxacin dose.
Nitrofurantoin
In vitro, nitrofurantoin antagonizes the antibacterial activity of norfloxacin. Since it is possible that antagonism could occur in vivo, norfloxacin and nitrofurantoin should not be used concomitantly.
Other Anti-infectives
In vitro, chloramphenicol, rifampin, or tetracycline can inhibit the bactericidal activity of norfloxacin. In an in vitro study, the combination of norfloxacin and chloramphenicol or tetracycline was antagonistic against all Salmonella isolates tested. In an in vitro study using strains of Ps. aeruginosa resistant to aminoglycosides and carbenicillin, the antibacterial activities of imipenem and norfloxacin were synergistic or partially synergistic against about one-third and indifferent against about two-thirds of strains tested; antagonism did not occur. In vitro studies using both gram-positive and gram-negative bacteria indicate that neither synergism nor antagonism occurs when norfloxacin is used in conjunction with a b-lactam antibiotic (e.g., ampicillin, cefotaxime, cefoxitin).
Probenecid
Concomitant administration of probenecid substantially decreases urinary excretion of norfloxacin, possibly by blocking renal tubular secretion of the anti-infective, but serum concentrations and half-life of norfloxacin generally are not affected.
Sucralfate
Concomitant administration of sucralfate may interfere with oral absorption of norfloxacin resulting in decreased serum and urine concentrations of the quinolone, and some clinicians state that concomitant use of ofloxacin with sucralfate is not recommended. If concomitant use of ofloxacin and sucralfate is necessary, the manufacturer and some clinicians recommend that doses of sucralfate not be ingested concomitantly with or within 2 hours of a norfloxacin dose.
Xanthine Derivatives
Concomitant use of some quinolones (e.g., ciprofloxacin, norfloxacin) in patients receiving theophylline has resulted in increased plasma theophylline concentrations and decreased clearance of the drug and may increase the risk of theophylline-related adverse effects.
There have been conflicting reports concerning the effect of norfloxacin on the pharmacokinetics of theophylline and additional study and experience are necessary to evaluate the interaction; however, the risk of norfloxacin inducing substantial alterations in theophylline pharmacokinetics appears to be less than with some other quinolones (e.g., ciprofloxacin)
Concomitant administration of norfloxacin and an extended-release theophylline preparation to a limited number of individuals produced only slight increases in serum theophylline concentrations compared with that of some other quinolone derivatives. In other studies, concomitant administration of norfloxacin in patients stabilized on theophylline resulted in at most an 18% increase in plasma theophylline concentrations and a decrease in theophylline clearance of 5-28%. Some clinicians suggest that the interaction between norfloxacin and theophylline may not be clinically important in most patients.
However, there have been reports of theophylline-related adverse effects in patients receiving norfloxacin concomitantly. Therefore, some clinicians suggest that norfloxacin be used with caution in patients receiving theophylline The manufacturer of norfloxacin states that consideration should be given to monitoring plasma theophylline concentrations and theophylline dosage should be adjusted as required. Some quinolones (e.g., ciprofloxacin) also have been reported to alter the pharmacokinetics of caffeine, and the possibility of exaggerated or prolonged effects of caffeine during concomitant use with a quinolone should be considered.