From the Guidelines
For nausea and vomiting following chemotherapy and immunotherapy when ondansetron (Zofran) is not effective, a multi-drug approach is recommended, prioritizing the use of a neurokinin-1 receptor antagonist such as aprepitant or fosaprepitant, along with dexamethasone and considering the addition of olanzapine, as supported by the most recent guidelines 1. When managing nausea and vomiting in this context, it's crucial to consider the emetogenic potential of the chemotherapy or immunotherapy regimen.
- The addition of dexamethasone 8-12mg IV/PO once daily is recommended, as it has been shown to enhance the efficacy of other antiemetic agents 1.
- A neurokinin-1 receptor antagonist such as aprepitant (125mg PO day 1, then 80mg days 2-3) or fosaprepitant (150mg IV single dose) should be considered, given their proven efficacy in preventing acute nausea and vomiting induced by highly emetogenic chemotherapy 1.
- The use of olanzapine, a second-generation antipsychotic, at a dose of 5-10mg PO daily for 3-4 days, is also recommended, as it works on multiple neurotransmitter receptors and has been shown to be effective in controlling chemotherapy-induced nausea and vomiting 1.
- For breakthrough symptoms, options include prochlorperazine 10mg IV/PO every 6 hours, metoclopramide 10mg IV/PO every 6 hours, or lorazepam 0.5-2mg IV/PO every 6 hours.
- Ensuring adequate hydration and considering IV fluids if dehydration occurs is vital, along with a thorough workup that includes complete blood count, comprehensive metabolic panel, and assessment for electrolyte imbalances, particularly hyponatremia and hypokalemia. These medications work through different antiemetic pathways, targeting serotonin, substance P, dopamine, and histamine receptors, providing more comprehensive control of chemotherapy-induced nausea and vomiting when a single agent is insufficient, as outlined in the NCCN guidelines 1.
From the Research
Medication Options for Nausea and Vomiting
When Zofran is not effective in managing nausea and vomiting following chemotherapy and immunotherapy, other medication options can be considered:
- Aprepitant, a neurokinin-1 receptor antagonist, has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) when used in combination with a 5-HT3 receptor antagonist and dexamethasone 2, 3, 4, 5
- Olanzapine, an atypical antipsychotic, has been studied as a potential treatment for breakthrough nausea and vomiting, with a recommended dose of 10 mg orally daily for 3 days 2
- Palonosetron, a second-generation 5-HT3 receptor antagonist, has also been shown to be effective in preventing CINV, particularly when combined with aprepitant and dexamethasone 6
Workup and Prevention Strategies
To prevent nausea and vomiting following chemotherapy and immunotherapy:
- A combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy for the prophylaxis of acute and delayed emesis 2, 3, 4, 5
- For patients undergoing multiple-day chemotherapy, a 5-HT3 receptor antagonist, dexamethasone, and aprepitant are recommended before chemotherapy for the prophylaxis of acute and delayed emesis 2
- For patients experiencing breakthrough nausea and vomiting, olanzapine may be considered as a treatment option, although mild to moderate sedation is a potential side effect, particularly in elderly patients 2
Considerations and Side Effects
When using these medication options, consider the following:
- Aprepitant is generally well tolerated, but fatigue is a common side effect, and it can interact with other medications due to its effects on cytochrome P450 3A4 3, 4, 5
- Olanzapine can cause mild to moderate sedation, particularly in elderly patients, and should be used with caution in this population 2