How to manage acute diarrhea as a side effect of Zepbound (tirzepatide)?

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Last updated: May 29, 2025View editorial policy

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From the Guidelines

To manage Aga diarrhea side effect of Zepbound, patients should start with oral hydration, dietary modification, and consider taking loperamide (4 mg initially, 2 mg after every loose stool to a maximum of 16 mg/day) as recommended by the Annals of Oncology guidelines 1. When managing diarrhea as a side effect of Zepbound, it's essential to prioritize hydration and dietary adjustments.

  • Staying well-hydrated is crucial to prevent dehydration and electrolyte imbalances.
  • Temporarily adjusting the diet to include more binding foods like bananas, rice, toast, and applesauce (BRAT diet) can help alleviate symptoms.
  • Avoiding foods that can worsen diarrhea, such as spicy, greasy, or high-fiber items, as well as caffeine and alcohol, is also recommended. The use of loperamide (Imodium) can be effective for short-term relief, with an initial dose of 4 mg followed by 2 mg every 4 hours or after every unformed stool, not to exceed 16 mg/day, as suggested by the ESMO clinical practice guidelines 1. It's also important to notify the treating physician and avoid skin irritation, especially in patients who are incontinent of stool due to the risk of pressure ulcer formation 1. If diarrhea persists beyond 2-3 days, is severe, or is accompanied by fever, severe abdominal pain, or blood in stool, patients should contact their healthcare provider immediately, as they may need to adjust the Zepbound dosage or recommend a slower dose escalation schedule.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Managing Aga Diarrhea Side Effect of Zepbound

To manage Aga diarrhea, a side effect of Zepbound, the following options can be considered:

  • Loperamide, an antidiarrheal medication, can be used to control diarrhea symptoms 2
  • Loperamide works by decreasing peristalsis and fluid secretion, resulting in longer gastrointestinal transit time and increased absorption of fluids and electrolytes from the gastrointestinal tract 2
  • It is available without a prescription and has minimal central nervous system effects due to its low oral absorption and inability to cross the blood-brain barrier 2
  • Opioid receptor agonists, such as loperamide, have been shown to reduce stool frequency and increase transit time in patients with chronic idiopathic diarrhea 3
  • Loperamide has also been found to improve stool consistency and reduce abdominal pain and urgency compared to placebo 3

Potential Interactions and Side Effects

  • Concurrent administration of loperamide with CYP3A4 inhibitors may elevate loperamide concentrations 2
  • Common adverse reactions to loperamide include cramps and nausea 2
  • Further evidence is needed from larger, prospective studies to fully understand the effects of opioids in the management of chronic idiopathic diarrhea 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Loperamide: a pharmacological review.

Reviews in gastroenterological disorders, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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