Drug Interaction Report

Coadministration with rizatriptan may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6. Rizatriptan has been shown to be a competitive inhibitor of CYP450 2D6 in vitro, but only at high, clinically irrelevant concentrations and a clinically significant inhibitory effect on CYP450 2D6 has not been demonstrated in clinical drug interaction studies. Based on these observations, rizatriptan may be administered with CYP450 2D6 substrates without the need for increased clinical monitoring

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.