Antacids, Sucralfate, Metal Cations, Multivitamins
Quinolones form chelates with alkaline earth and transition metal cations. Administration of quinolones with
antacids containing aluminum, magnesium, or calcium, with sucralfate, with metal cations such as iron, or with
multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as VIDEX
(didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with
the absorption of quinolones, resulting in systemic concentrations considerably lower than desired. These agents
should not be taken within 4 hours before or 4 hours after grepafloxacin administration.
Raxar, like other quinolones, may inhibit the metabolism of caffeine and theobromine. These stimulants are
commonly found in coffee and tea, respectively. In some patients, this may lead to reduced clearance, prolongation of
plasma half-life, and enhanced effects of caffeine and theobromine.
Raxar is a competitive inhibitor of the metabolism of theophylline. Serum theophylline concentrations
increase when grepafloxacin is initiated in a patient maintained on theophylline. When initiating a multi-day
course of grepafloxacin in a patient maintained on theophylline, the theophylline maintenance dose should be halved
for the period of concurrent use of grepafloxacin and monitoring of serum theophylline concentrations should be
initiated as a guide to further dosage adjustments.
In subjects receiving warfarin, no significant change in clotting time was observed when grepafloxacin was
coadministered. However, because some quinolones have been reported to enhance the effects of warfarin or its
derivatives, prothrombin time or other suitable anticoagulation test should be monitored closely if a quinolone
antimicrobial is administered with warfarin or its derivatives.
Drugs Metabolized by Cytochrome P450 Enzymes
The drug interaction study evaluating the effect of grepafloxacin on theophylline indicates that grepafloxacin
inhibits theophylline metabolism, which is mediated by CYP1A2. While no clinical studies have been conducted to
evaluate the effect of grepafloxacin on the metabolism of C.P.A. substrates, in vitro data suggest similar
effects of grepafloxacin in CYP3A4 mediated metabolism and theophylline metabolism. In addition, other quinolones
have been reported to decrease the CYP3A4-mediated metabolism of cyclosporine. Other drugs metabolized by C.P.A.
include terfenadine, astemizole, cisapride, midazolam, and triazolam. The clinical relevance of the potential effect
of grepafloxacin on the metabolism of C.P.A. substrates is not known. Patients receiving concurrent administration of
substrates of C.P.A. were not excluded from clinical trials of grepafloxacin.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
The concomitant administration of a nonsteroidal anti inflammatory drug with a quinolone may increase the risks of
CNS stimulation and convulsions.
Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated
concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is
recommended when these agents are coadministered.