Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the organic anion transporting polypeptide (OATP) 1B3 hepatic uptake transporter and/or the hepatic bile acid uptake transporter sodium taurocholate co-transporting polypeptide (NTCP) may significantly increase the plasma concentrations and effects of zavegepant, which is a substrate of these transporters. When single-dose oral zavegepant (100 mg) was administered with the OATP 1B3 and NTCP inhibitor and strong CYP450 3A4 inducer, rifampin, at steady state, zavegepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.3-fold, respectively.

MANAGEMENT: Concomitant use of zavegepant with OATP 1B3 and/or NTCP inhibitors should generally be avoided.

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).