Drug Interactions between Dexamethasone Intensol and fosaprepitant

ADJUST DOSE: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of some corticosteroids. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. According to the product labeling, coadministration of aprepitant (125 mg on day 1 and 80 mg/day on days 2 through 5) and dexamethasone (20 mg orally on day 1 and 8 mg on days 2 through 5) resulted in an increase in the area under the plasma concentration-time curve (AUC) of dexamethasone by 2.2-fold on days 1 and 5. Similarly, aprepitant (125 mg on day 1 and 80 mg/day on days 2 and 3) increased the AUC of methylprednisolone (125 mg intravenously on day 1 and 40 mg orally on days 2 and 3) by 1.34-fold on day 1 and 2.5-fold on day 3. In contrast, coadministration with a single 40 mg dose of aprepitant increased the AUC of oral dexamethasone (20 mg) by just 45%, indicating a weaker inhibition of CYP450 3A4 during low-dose, single administration. The effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is also expected to be smaller when the substrates are administered intravenously as opposed to orally, and may be altered following prolonged administration.

MANAGEMENT: Oral dexamethasone and methylprednisolone dosage should be reduced by approximately 50% when coadministered with the aprepitant 125 mg/80 mg regimen, and intravenous methylprednisolone dosage should be reduced by approximately 25%. The daily dosage of dexamethasone administered in clinical chemotherapy-induced nausea and vomiting studies with aprepitant was reduced to account for the drug interaction. No dosage adjustment for the corticosteroid is necessary during coadministration with aprepitant in a single 40 mg dose for prevention of postoperative nausea and vomiting. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended, as it has not been studied and the drug interaction profile may change during long-term use.