Aprepitant (Emend®) for Ablative Regimens

Last Modified: July 1, 2007

Dear OncoLink "Ask The Experts,"

Have there been any studies done on the efficacy of Emend for use in ablative chemotherapy? If not what is your recommendation for combating nausea from an 8- day regimen of Busulfan and Cyclophosphamide?

Michael Vozniak, PharmD, BCOP, Hematology/Oncology Clinical Pharmacy Specialist, responds:

At the 2007 ASCO meeting, an abstract was presented (#9112) looking at the addition of aprepitant to standard anti-emetics (ondansetron + dexamethasone). Although it was a small number of patients and full results are not available in the abstract, the addition did provide improved emesis control.

At Penn, we do not have aprepitant on formulary. For our patients undergoing a busulfan (IV) plus cyclophosphamide transplant, we utilize single agent ondansetron, either 8mg PO/IV every 8 hours or 24mg PO/IV daily. We also order, as needed, lorazepam and promethazine to be given for breakthrough emesis. Anecdotally, our experience has been that IV busulfan causes less nausea and vomiting than PO busulfan did. Most institutions have moved exclusively to the use of IV busulfan at this time (with some exceptions), which avoids the problems with vomiting of partial dose and monitoring pharmacokinetics. Cyclophosphamide is notorious for causing delayed nausea and vomiting (>24 hours) and often times we need to schedule additional agents and not leave them on an as needed basis.

Several years ago, I recall utilizing aprepitant on a few bone marrow transplant patients with refractory nausea and vomiting, but I do not recall the details of their conditioning regimen. Obviously, we would consider using aprepitant if all else failed in our patients.

One concern with aprepitant is drug interactions, as it is metabolized through the liver using the cytochrome P450 isoenzyme system, particularly 3A4. Both cyclophosphamide and busulfan are substrates of 3A4; therefore, there is the potential for drug interactions to occur between aprepitant and the chemotherapy. The abstract presented at ASCO performed pharmacokinetic analysis of cyclophosphamide and found no differences. Busulfan levels were monitored in the study, but drug interaction with aprepitant was not addressed.