Is There Rationale to Use an Antiemetic in the Same Class for the Treatment of Patients Who Experience Postoperative Nausea and Vomiting Despite Prophylaxis?

To the Editor: Current therapy of patients who have postoperative nausea and vomiting (PONV) despite prophylaxis is to switch to a different antiemetic from another class (1). A redosing study (2) determined that when intraoperative prophylactic ondansetron was unsuccessful, repeating it in the PACU did not have additional efficacy. Redosing studies in chemotherapy-induced nausea and vomiting (CINV) (3–5) suggest changing to a different member of the same 5-hydroxytryptamine (5-HT3) antagonist class allows increased efficacy. Although the 5-HT3 antagonists have structural similarities to serotonin, there are side chain differences. Granisetron’s effectiveness for failed ondansetron CINV patients may be related to side chain differences and increased receptor binding. Granisetron is highly specific (1000:1) for the 5-HT3 receptor, but ondansetron also has nonspecific binding to 5-HT1A and 5-HT1B(6). Granisetron has a longer plasma half-life versus ondansetron (4.9 to 7.7 h (7) vs 3.5 to 5.5 h (8), respectively). Ondansetron’s metabolism is affected by variations of the cytochrome P450 CYP2D6 genotype, with ultrarapid metabolism causing decreased response to ondansetron (9).Granisetron is metabolized by CYP3A, not CYP2D6 (10), suggesting that granisetron may be able to rescue within class. Whether this observation is transferable from CINV to PONV, from ondansetron to other same-class members and vice versa, suggests lessons from the CINV model and merits a PONV study. Anthony L. Kovac, MD