Serotonin 5-HT₃ receptor antagonists are FDA-approved for the prevention of chemotherapy-induced nausea and vomiting (CINV), radiotherapy-induced nausea and vomiting (RINV), and post-operative nausea and vomiting (PONV)^{1, 2}. Although not FDA-approved, these agents have also been utilized in the treatment of opioid-induced nausea, nausea and vomiting of pregnancy (hyperemesis gravidarum), and acute pediatric gastroenteritis^{1, 2}. The American Society of Clinical Oncology (ASCO) antiemetic guidelines recommend the use of 5-HT₃ receptor antagonists in conjunction with dexamethasone, a neurokinin 1 (NK₁) receptor antagonist, and olanzapine to manage nausea and vomiting associated with highly emetogenic antineoplastic agents. Additionally, the guidelines recommend a 5-HT₃ receptor antagonist combined with dexamethasone and a NK₁ receptor antagonist for control of nausea and vomiting associated with moderately emetogenic carboplatin with an area under the curve (AUC) of greater than or equal to 4 mg/mL/min. The guidelines recommend that other antineoplastic agents with a moderate emetic risk should be managed with a two-drug combination of a 5-HT₃ receptor antagonist combined with dexamethasone⁴. A single dose of a 5-HT₃ receptor antagonist or dexamethasone is recommended for use with low emetic risk chemotherapy regimens, while no antiemetic is recommended for use with chemotherapy regimens having minimal emetic risk. ASCO also recommends 5-HT₃ receptor antagonist use—often in conjunction with dexamethasone—to manage nausea and vomiting associated with minimal, low, moderate, and high emetic risk radiation therapy^{3, 4}. A combination product containing palonosetron, a serotonin 5-HT₃ receptor antagonist, and netupitant, a selective substance P selective neurokinin 1 receptor antagonist is available for use in combination with dexamethasone in adults to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of cancer therapy, including, but not limited to, highly emetogenic chemotherapy⁵. Recommended FDA-approved dosage regimens for the available serotonin 5-HT₃ receptor antagonists are summarized in Tables 1 and 2. Dosages exceeding these recommendations will be reviewed.

Legend:

• * Doses should be administered within 1 hour before chemotherapy, radiation, or induction of anesthesia
• ** Doses should be administered within 2 hours before surgery or radiation
• *** Patch should be applied within 24 to 48 hours before chemotherapy begins and removed a minimum of 24 hours after therapy completion; patch can be worn for up to 7 days depending on the duration of chemotherapy
• † Doses should be given 30 minutes before the start of single-day therapy
• ≠ First dose should be given 30 minutes before the start of chemotherapy, with a second dose 8 hours after the first dose, followed by 8 mg twice daily (every 12 hours) continued for 1 to 2 days after completion of chemotherapy
• †† Subsequent doses should be given every 8 hours after the first dose and continued for 1 to 2 days after completion of radiotherapy
• ††† Subsequent doses should be given every 8 hours after the first dose each day radiotherapy is given

Legend:

• * Doses should be administered within 1 hour before chemotherapy, radiation, or induction of anesthesia
• + For highly emetogenic chemotherapy, given concurrently with dexamethasone on days 1-4; with moderately emetogenic chemotherapy, given concurrently with dexamethasone on day 1

Table 3 summarizes the current pediatric FDA-approved indications and dosages of the available serotonin 5-HT₃ receptor antagonists. Dolasetron and ondansetron are the only oral serotonin 5-HT₃ receptor antagonists FDA-approved for the prevention of CINV in children ¹. Currently, there are no oral 5-₃ receptor antagonists approved for preventing PONV in children. Dolasetron is approved for use in children greater than 2 years of age; safety and efficacy in children less than 2 years of age have not been established ^1,2,6 . Ondansetron is approved for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in children 4 years of age and older. There are no data available addressing the use of 24 mg ondansetron tablets for highly emetogenic chemotherapy in children^{1, 2, 9}. Safety and efficacy of granisetron in children less than 18 years of age have not been established^{1, 2, 7, 8}. Netupitant/palonosetron combination therapy is not approved in pediatric patients as safety and efficacy data are not available for this agent in this patient population^{1, 2, 5}. No data are available evaluating serotonin 5-HT₃ receptor antagonists for the use of RINV in pediatric patients.

Legend:

• * Doses should be administered within 1 hour before chemotherapy
• # For children who cannot take 100 mg due to weight or ability to swallow tablets, the injection solution may be mixed into apple or apple-grape juice for oral dosing in pediatric patients
• ** The first dose should be given 30 minutes before the start of chemotherapy, with a second dose 8 hours after the first dose, followed by 8 mg twice daily (every 12 hours) continued for 1 to 2 days after completion of chemotherapy
• † The first dose should be given 30 minutes before the start of chemotherapy, with subsequent doses 4 and 8 hours after the first dose, followed by 4 mg three times daily (every 8 hours) continued for 1 to 2 days after completion of chemotherapy