What is the treatment for medication-induced nausea and vomiting?

Treatment of Zepbound-Induced Nausea and Vomiting

For Zepbound (tirzepatide)-induced nausea and vomiting, start with ondansetron 8 mg orally three times daily or metoclopramide 10-20 mg orally three to four times daily as first-line therapy. 1

First-Line Antiemetic Options

Serotonin (5-HT3) Antagonists

• Ondansetron 16-24 mg orally once daily is the preferred initial approach for medication-induced nausea 1
• Alternatively, ondansetron 8 mg IV can be administered if oral intake is not tolerated 2, 3
• Administer 30-60 minutes before anticipated nausea or at symptom onset 1, 2
• Other equivalent 5-HT3 antagonists include granisetron 2 mg orally once daily or tropisetron 5 mg orally once daily 1

Dopamine Antagonists

• Metoclopramide 20-30 mg orally, given 3-4 times daily is an effective alternative 1
• Prochlorperazine 10-20 mg orally, 3-4 times daily can also be used 1
• These agents work through different mechanisms than 5-HT3 antagonists and may be preferred in some patients 4

Refractory Symptoms

If nausea and vomiting persist despite monotherapy:

• Add a dopamine antagonist to the serotonin antagonist regimen for breakthrough symptoms 1
• Consider dexamethasone 20 mg orally once daily as adjunctive therapy, though this is primarily studied in chemotherapy-induced nausea 1
• Lorazepam 1-2 mg orally, 1-4 times daily can be added for anticipatory nausea or anxiety-related symptoms 1

Important Clinical Considerations

Route of Administration

• Oral formulations are preferred for routine use and are equally effective when tolerated 1
• Switch to IV administration if the patient is actively vomiting to ensure adequate drug delivery 1, 2

Timing and Duration

• Antiemetics should be given 30-60 minutes before the next Zepbound dose if nausea is predictable 1, 2
• For persistent symptoms, continue scheduled dosing rather than as-needed administration 5
• Use antiemetics for the shortest duration necessary to control symptoms 5

Common Pitfalls

• Headache and constipation are the most common side effects of ondansetron and should be anticipated 6, 7
• Ondansetron may cause CNS side effects and requires dose adjustment in hepatic impairment 7
• Dolasetron should be avoided in patients with cardiac conduction abnormalities due to cardiovascular effects 7
• Metoclopramide carries risk of extrapyramidal symptoms, particularly with prolonged use 6

Alternative Causes to Exclude

Before attributing symptoms solely to Zepbound, consider other contributing factors including: infection, metabolic disorders, electrolyte disturbances, constipation, gastrointestinal obstruction, or concurrent medications (opioids, antibiotics, antifungals) 1

Practical Algorithm

1. Start with ondansetron 16-24 mg orally once daily (or 8 mg IV if vomiting) 1, 2
2. If inadequate response after 24-48 hours, add metoclopramide 20-30 mg orally 3-4 times daily 1
3. For persistent symptoms, consider adding lorazepam 1-2 mg for anxiety component 1
4. If symptoms remain refractory, switch to IV ondansetron 8 mg and evaluate for alternative causes 2, 3