Drug interactions between levofloxacin and sevelamer

ADJUST DOSING INTERVAL: Concurrent administration of sevelamer hydrochloride may decrease the oral bioavailability of ciprofloxacin and other quinolones, potentially reducing antibiotic efficacy and increasing the risk of bacterial resistance. The proposed mechanism is reduced quinolone absorption due to chelation with the protonated amine groups of sevelamer in the intestine. In 15 healthy volunteers, administration of sevelamer hydrochloride (7 X 403 mg capsules) followed immediately by a single dose of ciprofloxacin 750 mg resulted in decreased peak plasma concentration (Cmax) and relative oral bioavailability of ciprofloxacin by 27% and 48%, respectively, compared to administration of ciprofloxacin alone. The interaction was subject to a high degree of interindividual variation. Compared with ciprofloxacin alone, the relative oral bioavailability of ciprofloxacin ranged from 0.27 to 1.16 when coadministered with sevelamer. Two subjects had increased ciprofloxacin systemic exposure (AUC) with sevelamer. No data are available for other quinolones but a similar interaction should be expected.

MANAGEMENT: Oral quinolone antibiotics should not be administered simultaneously with sevelamer hydrochloride. The optimal length of time needed to separate ingestion of these drugs is currently unknown. Based on the fact that it took up to 4 hours to achieve ciprofloxacin Cmax in all 15 volunteers of the study, the authors suggested a separation time of at least 4 hours between sevelamer and ciprofloxacin administration to reduce the likelihood of a significant interaction, particularly in patients with end-stage renal disease whose gastrointestinal motility may be slowed.