Ondansetron Aprepitant

In a crossover study in 20 subjects, aprepitant 125 mg on day one, and 80 mg on days 2 to 5 given with a standard dexamethasone regimen (20 mg on day one, and 8 mg on days 2 to 5) increased the dexamethasone AUC by 2.2-fold. When the same dose of aprepitant was given with a reduced-dose dexamethasone regimen (12 mg on day one, and 4 mg on days 2 to 5), the AUC of dexamethasone was similar to that seen with the standard dexamethasone regimen given alone. All regimens in this study also included intravenous ondansetron 32 mg on day one. ... 

Aprepitant had no clinically relevant effect on the pharmacokinetics of dolasetron, granisetron, ondansetron or palonosetron. 

No important pharmacokinetic interactions occur, therefore no dosage adjustment is required when aprepitant is given with dolasetron, ondansetron, granisetron or palonosetron. 

Blum RA, Majumdar A, McCrea J, Busillo J, Orlowski LH, Panebianco D, Hesney M, Petty KJ, Goldberg MR, Murphy MG, Gottesdiener KM, Hustad CM, Lates C, Kraft WK, Van Bu-ren S, Waldman SA, Greenberg HE. Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther (2003) 25, 1407-19. 

The use of aprepitant has also been shown to increase the activity of the 5-HT3 receptor antagonist ondansetron and the corticosteroid dexamethasone, which are also used to prevent the acute phase of CINV caused by chemotherapy. 

A combined analysis of the two studies demonstrates that both aprepitant doses (40 and 125 mg) improved protection against nausea and vomiting and reduced the need for rescue therapy, compared with ondansetron. The 40 mg aprepitant dose also was found to be superior to ondansetron for the prevention of nausea, vomiting, and the need to use rescue therapy in the same patient. 

Currently, the most expensive drug for chemotherapy-induced nausea and vomiting is aprepitant since the generic version of ondansetron became available in 2007. A 4 mg dose of ondansetron may now cost the patient less than 20.00. The addition of 403 aprepitant to this standard regimen increases the cost... 

Monotherapy as noted above, for the treatment of PONV, aprepitant when used as a single antiemetic agent was superior to ondansetron in preventing nausea and vomiting as well as decreasing the need for rescue therapy. 

Multimodal therapy the addition of aprepitant to the combined ondansetron and dexamethasone regimen demonstrated a decrease in both the acute and delayed phases of chemotherapy-induced emesis. 

The results of various clinical trials indicated that the incidence of adverse events was similar in the aprepitant group compared with the group which received only standard regimen of ondansetron and dexamethasone. The most commonly observed side effects with aprepitant treatment were asthenia, hiccups, diarrhea, gastritis, elevation in fiver function tests, and dizziness. There are also reports of thrombocytopenia and dehydration. 

Gan T, et al. A randomized, double-blind comparison of the NKl-antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Ana/g2007 104 1082-1089. 

---