Drug Interaction Report

MONITOR: Coadministration with phenytoin may reduce the plasma concentrations and antimicrobial efficacy of erythromycin and other macrolide antibiotics. The mechanism is induction of CYP450 3A metabolism by phenytoin. Additionally, plasma concentrations of phenytoin may be increased. One study has suggested that the pharmacokinetic disposition of phenytoin is not significantly altered in patients receiving erythromycin. However, occasional large changes in phenytoin clearance were noted in some patients.

MANAGEMENT: If concomitant use is medically necessary, caution and monitoring for altered efficacy and safety of both medications is recommended.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.