Drug Interactions between didanosine and grepafloxacin

ADJUST DOSING INTERVAL: The concomitant administration with didanosine buffered tablets or pediatric oral solution may reduce the oral bioavailability of grepafloxacin and other quinolone antibiotics. The mechanism is reduced quinolone absorption due to chelation with metallic cations from buffering agents and antacids used in certain formulations of didanosine. According to the manufacturer, administration with 1 gram of aluminum hydroxide reduced the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 200 mg dose of grepafloxacin by approximately 60% each. The pharmacokinetics of grepafloxacin have not been studied in combination with the various didanosine formulations, but significant reductions in bioavailability have been reported for ciprofloxacin, another quinolone, in interaction studies with didanosine.

MANAGEMENT: Grepafloxacin should be administered at least 4 hours before or 4 hours after didanosine buffered tablets or pediatric oral solution, and patients should be monitored for potentially decreased antimicrobial efficacy during concomitant therapy. Didanosine buffered powder for oral solution, which uses a citrate-phosphate buffer, and the delayed-release capsules, which are not buffered, are not expected to cause this interaction.