Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of gefitinib, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of gefitinib (250 mg single dose) with the potent inhibitor itraconazole (200 mg once a day for 12 days) increased the mean gefitinib systemic exposure (AUC) by 88% in healthy male volunteers. This increase may be clinically significant, as adverse events of gefitinib are related to dose and exposure.

MANAGEMENT: Caution is advised if gefitinib is administered with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, conivaptan, idelalisib, nefazodone, cobicistat, delavirdine, and most protease inhibitors. Pharmacologic response to gefitinib should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary. Patients should be advised to contact their physician if they experience possible symptoms of gefitinib toxicity such as severe diarrhea, nausea, dyspnea, cough, and fever.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of gefitinib, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of gefitinib (250 mg single dose) with the potent inhibitor itraconazole (200 mg once a day for 12 days) increased the mean gefitinib systemic exposure (AUC) by 88% in healthy male volunteers. This increase may be clinically significant, as adverse events of gefitinib are related to dose and exposure.

MANAGEMENT: Caution is advised if gefitinib is administered with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, conivaptan, idelalisib, nefazodone, cobicistat, delavirdine, and most protease inhibitors. Pharmacologic response to gefitinib should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary. Patients should be advised to contact their physician if they experience possible symptoms of gefitinib toxicity such as severe diarrhea, nausea, dyspnea, cough, and fever.

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.