Drug Interactions between didanosine and trovafloxacin

ADJUST DOSING INTERVAL: Concomitant administration with didanosine buffered tablets or pediatric oral solution may reduce the oral bioavailability of trovafloxacin 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. In 12 healthy volunteers, administration of an antacid containing aluminum hydroxide-magnesium hydroxide (3600 mg-1800 mg/30 mL dose) 0.5 hour before and 2 hours after a single 300 mg dose of trovafloxacin reduced the mean peak plasma concentration (Cmax) of trovafloxacin by 61% and 11% and its area under the concentration-time curve (AUC) by 66% and 28%, respectively. The pharmacokinetics of trovafloxacin 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: Trovafloxacin should be administered at least 2 hours before or 2 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.