What is the best antiemetic medication to give on a scheduled basis if Reglan (Metoclopramide) and Zofran (Ondansetron) are ineffective, and what is the recommended dose and frequency?

From the Guidelines

If Reglan (metoclopramide) and Zofran (ondansetron) are ineffective for nausea, Palonosetron is a suitable alternative, typically dosed at 0.25 mg IV once, due to its higher binding affinity for the 5-HT3 receptor and longer half-life compared to other serotonin antagonists 1.

Key Considerations

• Palonosetron has been shown to be effective in preventing both acute and delayed emesis associated with moderately emetogenic chemotherapy, with a single intravenous dose being comparable to other 5-HT3 antagonists for acute emesis but superior for delayed emesis 1.
• The choice of antiemetic medication depends on the cause of nausea, patient-specific factors, and side effect profiles, with palonosetron offering a favorable profile due to its efficacy and safety data 1.
• Dexamethasone is often used in combination with 5-HT3 receptor antagonists, including palonosetron, to enhance antiemetic efficacy, with a recommended dose of 12 mg PO/IV once when used with aprepitant or other NK1 receptor antagonists 1.

Alternative Options

• Other 5-HT3 receptor antagonists like granisetron and ondansetron can be considered, with dosing regimens including 10 mg SQ once, 2 mg PO once, or 0.01 mg/kg (max 1 mg) IV once for granisetron, and 16-24 mg PO once or 8-16 mg IV once for ondansetron 1.
• Aprepitant and its intravenous formulation fosaprepitant are also options for preventing acute and delayed emesis, particularly when used in combination with dexamethasone and a 5-HT3 receptor antagonist, with recommended doses of 125 mg PO once for aprepitant and 115 mg IV once for fosaprepitant on day 1 of a 3-day regimen 1.

Clinical Decision Making

• The selection of an antiemetic regimen should be guided by the emetogenic potential of the chemotherapy, patient factors, and the efficacy and safety profiles of the available medications, with palonosetron offering a valuable option for patients who have not responded to metoclopramide and ondansetron 1.

From the FDA Drug Label

The use of aprepitant did not affect the time to first use of rescue medication when compared to ondansetron However, compared to the ondansetron group, use of aprepitant delayed the time to first vomiting, as depicted in Figure 3 Aprepitant Capsules USP, 40 mg: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Aprepitant is an option for preventing nausea when Reglan and Zofran do not work.

• The dose of aprepitant is 40 mg.
• The frequency of administration is a single dose. 2

From the Research

Alternative Antiemetic Options

If Reglan and Zofran are ineffective, alternative antiemetic options can be considered.

• Aprepitant has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) 3.
• Aprepitant can be used in combination with other antiemetics, such as ondansetron and dexamethasone, to provide superior efficacy in the treatment of CINV 3.
• Metoclopramide can also be used as an alternative antiemetic option, particularly in patients who have not responded to other treatments 4, 5.

Dose and Frequency

The dose and frequency of alternative antiemetic options may vary depending on the specific medication and patient population.

• Aprepitant is typically administered orally, with a dose of 125 mg on day 1, followed by 80 mg on days 2-3 3, 4.
• Metoclopramide can be administered orally or intravenously, with a dose of 20 mg four times daily 4, 5.
• Palonosetron can be administered intravenously, with a dose of 0.25 mg on day 1 5.
• Dexamethasone can be administered orally or intravenously, with a dose of 8-12 mg on days 1-3 3, 4, 5.

Efficacy and Safety

The efficacy and safety of alternative antiemetic options have been evaluated in several studies.

• Aprepitant has been shown to be generally well tolerated, with a similar incidence of adverse events compared to control groups 3.
• Metoclopramide has been associated with a higher incidence of extrapyramidal effects and diarrhea compared to ondansetron 6.
• Palonosetron has been shown to be noninferior to dexamethasone in terms of delayed total control rate in patients undergoing MEC 5.