Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and efflux transporter. When apixaban was coadministered with the moderate CYP450 3A4 and P-gp inhibitor diltiazem (360 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.4-fold, respectively. Likewise, coadministration with the P-gp inhibitor naproxen (500 mg single dose) increased the mean apixaban Cmax and AUC by approximately 1.6- and 1.5-fold, respectively.

MANAGEMENT: No dosage adjustment for apixaban is required during concomitant therapy with lone inhibitors of CYP450 3A4 or P-gp, or moderate or weak dual inhibitors of both CYP450 3A4 and P-gp. However, caution may be advisable. Closer monitoring of the pharmacologic effects of apixaban may be appropriate whenever a CYP450 3A4 or P-gp inhibitor is added to or withdrawn from therapy. Patients should be routinely evaluated for signs and symptoms suggesting blood loss such as a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress (in pregnant women).

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and efflux transporter. When apixaban was coadministered with the moderate CYP450 3A4 and P-gp inhibitor diltiazem (360 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.4-fold, respectively. Likewise, coadministration with the P-gp inhibitor naproxen (500 mg single dose) increased the mean apixaban Cmax and AUC by approximately 1.6- and 1.5-fold, respectively.

MANAGEMENT: No dosage adjustment for apixaban is required during concomitant therapy with lone inhibitors of CYP450 3A4 or P-gp, or moderate or weak dual inhibitors of both CYP450 3A4 and P-gp. However, caution may be advisable. Closer monitoring of the pharmacologic effects of apixaban may be appropriate whenever a CYP450 3A4 or P-gp inhibitor is added to or withdrawn from therapy. Patients should be routinely evaluated for signs and symptoms suggesting blood loss such as a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress (in pregnant women).

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.