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

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Last updated: May 29, 2025View editorial policy

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From the Guidelines

To manage diarrhea as a 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, up to 16 mg/day) as recommended by the most recent guidelines 1. The management of diarrhea side effects of Zepbound should prioritize measures to prevent dehydration and electrolyte imbalances.

  • Staying well-hydrated is crucial, and patients can achieve this by drinking plenty of fluids, such as water, clear broths, or electrolyte-rich beverages like sports drinks.
  • Temporarily adjusting the diet to include more bland, low-fiber foods like bananas, rice, toast, and applesauce, while avoiding spicy, fatty, or high-fiber foods, can help minimize digestive disturbances.
  • Over-the-counter medications such as loperamide (Imodium) can be taken as directed, but it's essential to follow the recommended dosage to avoid adverse effects. If diarrhea persists beyond 2-3 days, is severe, contains blood, or is accompanied by fever or severe abdominal pain, patients should contact their healthcare provider immediately 1. For many patients, gastrointestinal side effects of Zepbound tend to improve over time as the body adjusts to the medication.
  • The healthcare provider might recommend a temporary dose reduction if symptoms are severe or persistent.
  • Staying on a regular eating schedule with smaller, more frequent meals can also help minimize digestive disturbances. These side effects occur because Zepbound slows gastric emptying and affects gut hormone signaling, which can alter digestive processes while the body adapts to the medication 1.

From the Research

Managing Diarrhea Side Effect of Zepbound

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

  • Loperamide: Studies have shown that loperamide is a safe and effective antidiarrheal for the treatment of acute diarrhea 2, 3, 4. It has been compared with bismuth subsalicylate and found to be more effective in reducing the average number of unformed bowel movements and providing faster relief.
  • Bismuth subsalicylate: Although loperamide has been found to be more effective, bismuth subsalicylate can still be beneficial in preventing and treating infectious diarrhea, including traveler's diarrhea 5. It has been shown to have bacteriostatic/bactericidal effects against a variety of pathogenic gastrointestinal bacteria.

Comparison of Loperamide and Bismuth Subsalicylate

The studies suggest that:

  • Loperamide is more effective than bismuth subsalicylate in reducing the average number of unformed bowel movements and providing faster relief 3, 4.
  • Loperamide is safe and well-tolerated, with few adverse reactions reported 2, 3, 4.
  • Bismuth subsalicylate can be beneficial in preventing and treating infectious diarrhea, including traveler's diarrhea 5.

Treatment Options

Based on the studies, the following treatment options can be considered:

  • Loperamide hydrochloride (Imodium A-D) at a daily dosage limit of 8 mg (40 ml) 4.
  • Bismuth subsalicylate (Pepto-Bismol) at a daily dosage of 4.9 g 4.

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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