What are the management options for intractable nausea and vomiting?

From the Guidelines

Intractable nausea and vomiting management should start with metoclopramide, and for patients who fail this treatment, domperidone or 5-HT3 receptor antagonists like ondansetron or granisetron can be considered as the next line of treatment. The management of intractable nausea and vomiting requires a stepwise approach, targeting different pathways to provide relief to patients. According to a recent study 1, for patients who fail metoclopramide, domperidone, a dopamine D2-receptor antagonist, can be used, although its availability is limited in the United States. The recommended starting dose of domperidone is 10 mg 3 times a day, with a potential escalation to 20 mg 4 times a day, but this should be avoided due to cardiovascular safety considerations.

Treatment Options

• 5-HT3 receptor antagonists, such as ondansetron or granisetron, can be used to block serotonin receptors in the chemoreceptor trigger zone and inhibit vagal afferents, thereby improving nausea and vomiting 1.
• Neurokinin (NK-1) receptor antagonists, such as aprepitant, can be considered for refractory cases, as they have shown improvement in nausea and vomiting in patients with gastroparesis 1.
• Phenothiazine antipsychotics, such as prochlorperazine, can also be used to reduce nausea and vomiting by inhibiting dopamine receptors in the brain.

Key Considerations

• The selection of treatment should be based on the patient's specific needs, including the presence of gastroparesis, and the potential side effects of each medication.
• The use of domperidone and other medications should be carefully monitored due to the potential risks of cardiac side effects and other adverse reactions.
• A comprehensive approach to managing intractable nausea and vomiting should include identifying and treating underlying causes, ensuring adequate hydration, and considering non-pharmacological approaches such as small, frequent meals and ginger supplements.

From the FDA Drug Label

In 2 randomized, double-blind, monotherapy trials, a single 24 mg oral dose of ondansetron tablets was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 Aprepitant capsules, in combination with other antiemetic agents, are indicated in patients 12 years of age and older for the prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)

For the management of intractable nausea and vomiting, the following options can be considered:

• Ondansetron: a single 24 mg oral dose can be effective in preventing nausea and vomiting associated with highly emetogenic cancer chemotherapy.
• Aprepitant: can be used in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy, as well as nausea and vomiting associated with moderately emetogenic cancer chemotherapy. It is essential to note that aprepitant has not been studied for the treatment of established nausea and vomiting 2. Therefore, it is not recommended for this purpose. In contrast, ondansetron has been shown to be effective in preventing nausea and vomiting associated with chemotherapy, but its effectiveness in treating established nausea and vomiting is not explicitly stated in the provided drug label 3.

From the Research

Intractable Nausea and Vomiting Management

• Nausea and vomiting are common symptoms that can reduce quality of life and indicate life-threatening illness, with acute symptoms lasting up to 7 days and chronic symptoms lasting 4 weeks or longer 4
• The differential diagnosis for chronic nausea and vomiting is broad, including gastrointestinal, infectious, metabolic, neurologic, psychiatric, or medication-related causes 4, 5
• A careful history of related factors is essential to guide the initial evaluation and narrow the differential diagnosis, including associated symptoms, timing of onset and duration of symptoms, exacerbating or relieving factors, alarm symptoms, medication and substance use, relationship with recent food ingestion, and comorbidities 4, 5

Nonpharmacologic Management

• Nonpharmacologic management options include fluid and electrolyte replacement, small, frequent meals, and avoidance of trigger foods 4
• These measures can help reduce symptoms and improve quality of life, especially in patients with acute nausea and vomiting 4

Pharmacologic Management

• Antiemetic drugs, such as serotonin antagonists (e.g., ondansetron) or dopamine antagonists, can effectively reduce symptoms of acute nausea and vomiting 4, 6, 7
• Ondansetron, a selective 5-HT3 receptor antagonist, has been shown to be effective in reducing nausea and vomiting associated with chemotherapy, anesthesia, and other causes 6, 7, 8
• The choice of pharmacologic agent and treatment duration should be individualized based on the underlying cause of symptoms, patient response, and potential side effects 4, 5, 7

Treatment Approach

• A practical 5-step approach to nausea and vomiting management includes defining the patient's symptoms, determining the duration and severity of symptoms, considering medication or toxin adverse effects, formulating a differential diagnosis, and directing treatment based on the underlying cause and neurotransmitters involved 5
• This approach can help guide the evaluation and treatment of patients with nausea and vomiting, improving outcomes and quality of life 5