Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein may increase the plasma concentrations of vismodegib, which has been shown in vitro to be a substrate of the efflux transporter. The potential for increased pharmacologic effects of vismodegib, including adverse effects such as muscle spasm, alopecia, dysgeusia/ageusia, weight loss, fatigue, nausea, vomiting, diarrhea, decreased appetite, constipation and arthralgia, should be considered.

MANAGEMENT: Caution is advised if vismodegib is used in combination with P-glycoprotein inhibitors.

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.