Drug Interaction Report

GENERALLY AVOID: Concurrent administration of guar gum may decrease the plasma levels of orally administered penicillins by reducing their absorption. In a study of 10 healthy volunteers administered phenoxymethyl penicillin with and without guar gum, both the peak serum concentration and the area under the serum concentration-time curve of penicillin were found to be significantly reduced by the gum.

MANAGEMENT: The use of guar gum should preferably be avoided during oral penicillin therapy. If these agents must be used together, separating the times of administration by as much as possible may help but has not been studied.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

ADJUST DOSING INTERVAL: Bulk-forming laxatives such as guar gum, psyllium, polycarbophil, or methylcellulose may affect the bioavailability of concomitantly administered substances due to their effect on the rate of gastrointestinal transit and gastric emptying.

MANAGEMENT: In general, oral medications should be administered at least 2 hours before or 2 hours after dosing of the bulk-forming laxative.

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.