ISTRATION).
Methylprednisolone: Oral aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.34-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was coadministered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. The I.V. methylprednisolone dose should be reduced by approximately 25%, and the oral methylprednisolone dose should be reduced by approximately 50% when coadministered with a regimen of fosaprepitant followed by aprepitant to achieve exposures of methylprednisolone similar to those obtained when it is given without aprepitant.
Chemotherapeutic agents: See PRECAUTIONS, General.
Docetaxel: In a pharmacokinetic study, oral aprepitant (CINV regimen) did not influence the pharmacokinetics of docetaxel.
Vinorelbine: In a pharmacokinetic study, oral aprepitant (CINV regimen) did not influence the pharmacokinetics of vinorelbine to a clinically significant degree.
Warfarin: A single 125-mg dose of oral aprepitant was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized on chronic warfarin therapy. Although there was no effect of oral aprepitant on the plasma AUC of R(+) or S(-) warfarin determined on Day 3, there was a 34% decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14% decrease in the prothrombin time (reported as International Normalized Ratio or INR) 5 days after completion of dosing with oral aprepitant. In patients on chronic warfarin therapy, the prothrombin time (INR) should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of fosaprepitant followed by aprepitant with each chemotherapy cycle.
Tolbutamide: Oral aprepitant, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of oral aprepitant and on Days 4, 8, and 15.
Oral contraceptives: Aprepitant, when given once daily for 14 days as a 100-mg capsule with an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of ethinyl estradiol by 43%, and decreased the AUC of norethindrone by 8%.
In another study, a daily dose of an oral contraceptive containing ethinyl estradiol and norethindrone was administered on Days 1 through 21, and oral aprepitant was given as a 3-day regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg I.V. on Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. In the study, the AUC of ethinyl estradiol decreased by 19% on Day 10 and there was as much as a 64% decrease in ethinyl estradiol trough concentrations during Days 9 through 21. While there was no effect of oral aprepitant on the AUC of norethindrone on Day 10, there was as much as a 60% decrease in norethindrone trough concentrations during Days 9 through 21. The coadministration of fosaprepitant or aprepitant may reduce the efficacy of hormonal contraceptives during and for 28 days after administration of the last dose of either. Alternative or back-up methods of contraception should be used during treatment with fosaprepitant and aprepitant and for 1 month following the last dose.
Midazolam: A study was completed with fosaprepitant and oral midazolam. Fosapre |
