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: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.