What are the first-line and second-line pharmacological treatments for managing vomiting?

Drug Therapy for Vomiting Management

First-Line Pharmacological Treatment

For general vomiting management, dopamine receptor antagonists (metoclopramide 10-40 mg PO/IV every 4-6 hours or prochlorperazine 10 mg PO/IV every 4-6 hours) are the recommended first-line agents, with 5-HT3 antagonists like ondansetron (8-16 mg PO/IV) reserved for breakthrough symptoms or when dopamine antagonists fail after 4 weeks. 1

Dopamine Antagonists as Initial Therapy

• Metoclopramide should be titrated to maximum benefit and tolerance, starting at 10-40 mg PO or IV every 4-6 hours PRN 2, 1
• Prochlorperazine 10 mg PO or IV every 4-6 hours PRN is an equally effective alternative 2, 1
• These agents work by blocking dopamine D2 receptors in the chemoreceptor trigger zone and have the added benefit of promoting gastric emptying with metoclopramide 1
• Monitor for extrapyramidal symptoms, particularly in young males, and treat with diphenhydramine 25-50 mg PO/IV every 4-6 hours if dystonic reactions occur 2

When to Add Corticosteroids

• Dexamethasone 12 mg PO or IV daily can be used as monotherapy for low emetic risk situations or combined with other agents for enhanced efficacy 2
• The combination of metoclopramide and dexamethasone is superior to either agent alone 3

Second-Line Pharmacological Treatment

5-HT3 Antagonists (Serotonin Antagonists)

If symptoms persist after 4 weeks of dopamine antagonist therapy, add ondansetron 8-16 mg PO or IV daily, as it acts on different receptors and provides complementary antiemetic coverage. 1

• Ondansetron 16 mg PO daily or 8 mg IV is the most studied 5-HT3 antagonist 2, 4, 5
• Alternative 5-HT3 antagonists include granisetron 1-2 mg PO daily, dolasetron 100 mg PO daily, or tropisetron 5 mg daily 2
• The maximum single IV dose of ondansetron is 16 mg due to cardiac safety concerns (QTc prolongation risk) 1, 6
• Monitor for QTc prolongation, especially when combining with other QT-prolonging agents 1

Combination Therapy Strategy

The general principle is to add agents from different drug classes rather than increasing doses of a single agent, as no single medication has proven superior for breakthrough emesis. 2, 1

• Combine ondansetron with dexamethasone 10-20 mg IV for superior antiemetic control compared to either agent alone 1
• Administer antiemetics on a scheduled basis rather than PRN, as prevention is far easier than treating established vomiting 1

Additional Second-Line Options

Benzodiazepines

• Lorazepam 0.5-2 mg PO or IV every 4-6 hours can be added for anticipatory nausea or as adjunctive therapy 2

Antipsychotics

• Haloperidol 0.5-2 mg PO or IV every 4-6 hours is an alternative dopamine antagonist with a different receptor profile than prochlorperazine 2, 1
• Olanzapine 2.5-5 mg PO BID is a category 2B recommendation for refractory cases 2

Cannabinoids (for Refractory Cases)

• Dronabinol 5-10 mg PO every 3-6 hours or nabilone 1-2 mg PO BID can be considered for refractory nausea 2

Anticholinergics

• Scopolamine 1 patch every 72 hours may be helpful for motion-related or vestibular causes 2

Context-Specific Considerations

Chemotherapy-Induced Vomiting

• For highly emetogenic chemotherapy: ondansetron 16-24 mg PO or 8-16 mg IV combined with NK1 receptor antagonist (aprepitant 125 mg day 1, then 80 mg days 2-3) plus dexamethasone 12 mg 6, 4
• For moderately emetogenic chemotherapy: ondansetron 8 mg PO BID or 8 mg IV plus dexamethasone 12 mg 6, 4
• When combining ondansetron with aprepitant, reduce corticosteroid dose by 50% due to CYP3A4 interactions 2, 6

Radiation-Induced Vomiting

• For upper abdomen radiation or total body irradiation: granisetron 2 mg PO daily or ondansetron 8 mg PO BID-TID, with or without dexamethasone 4 mg PO daily 2

Gastroenteritis-Related Vomiting

• Ondansetron 0.15 mg/kg IV (maximum 4 mg) or 0.2 mg/kg PO is effective for facilitating oral rehydration therapy 7, 8
• Note that ondansetron may increase stool volume/diarrhea in gastroenteritis 1

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension 1
• Avoid repeated endoscopy or imaging unless new symptoms develop 1
• Do not use promethazine IV peripherally—it must be given via central line only due to tissue necrosis risk 2
• Consider adding H2 blocker or proton pump inhibitor if dyspepsia is present, as patients may confuse heartburn with nausea 1
• Ensure adequate fluid intake of at least 1.5 L/day and consider thiamin supplementation to prevent Wernicke's encephalopathy in persistent vomiting 1

Algorithm for Route Selection

• Use oral route when patient can tolerate oral intake 2, 1
• Switch to IV route for persistent vomiting or inability to tolerate oral medications 2, 1
• Consider rectal suppositories (prochlorperazine 25 mg every 12 hours) when oral and IV routes are not feasible 2
• Sublingual formulations of ondansetron (oral dissolving tablets) are available for patients with difficulty swallowing 6