Drug Interaction Report

ADJUST DOSE: Concomitant administration of delavirdine and clarithromycin has been shown to increase the area under the plasma concentration-time curve (AUC) of clarithromycin by 100%. The mechanism may be related to inhibition of CYP450 3A4 hepatic metabolism.

MANAGEMENT: Close clinical monitoring for toxicity is recommended if this combination is used. The manufacturer recommends dose adjustments for clarithromycin in patients with renal insufficiency: Reduce the dose by 50% for patients with a creatinine clearance of 30 to 60 mL/min, and reduce by 75% for patients with creatinine clearance less than 30 mL/min.

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.

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.