Does Zetia (ezetimibe) cause heartburn?

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Last updated: January 19, 2026View editorial policy

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Does Zetia Cause Heartburn?

No, heartburn is not a recognized adverse effect of Zetia (ezetimibe) based on comprehensive guideline data and clinical trial experience.

Documented Adverse Effects of Ezetimibe

The American College of Cardiology's 2022 Expert Consensus provides the definitive list of adverse effects for ezetimibe, and heartburn is notably absent 1, 2:

As Monotherapy

  • Upper respiratory tract infection 1, 2
  • Diarrhea 1, 2
  • Arthralgia (joint pain) 1, 2
  • Sinusitis 1, 2
  • Pain in extremities 1, 2

In Combination with Statins

  • Nasopharyngitis 1, 2
  • Myalgia (muscle pain) 1, 2
  • Upper respiratory tract infection 1, 2
  • Arthralgia 1, 2
  • Diarrhea 1, 2

Why Ezetimibe Doesn't Cause Gastrointestinal Issues Like Other Lipid-Lowering Agents

Ezetimibe has a highly selective mechanism that distinguishes it from other intestinally-acting medications 3:

  • It specifically targets the NPC1L1 protein at the intestinal brush border to block cholesterol absorption 1, 3
  • Unlike bile acid sequestrants, it does not interfere with absorption of fat-soluble vitamins or other nutrients 3, 4
  • It does not affect triglyceride, bile acid, or fat-soluble vitamin absorption 4

Safety Profile

The safety profile of ezetimibe is comparable to placebo when used as monotherapy, based on large cardiovascular outcomes trials including IMPROVE-IT and SHARP 2:

  • The adverse event profile resembles placebo 5, 4
  • No clinically significant gastrointestinal disturbances beyond diarrhea have been reported 1

Clinical Implications

If a patient on ezetimibe reports heartburn, consider alternative causes 2:

  • Concomitant medications (especially statins, which can occasionally cause gastrointestinal symptoms)
  • Dietary factors
  • Gastroesophageal reflux disease (GERD) unrelated to ezetimibe
  • Other medical conditions

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Adverse Effects of Ezetimibe

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Ezetimibe's Effect on Nutrient Absorption

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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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