Most Common Side Effects of Zetia (Ezetimibe)
Primary Answer
The most common side effects of Zetia (ezetimibe) when used as monotherapy are upper respiratory tract infection, diarrhea, arthralgia (joint pain), sinusitis, pain in extremities, fatigue, and influenza, with an overall incidence similar to placebo. 1
Common Side Effects by Treatment Regimen
Ezetimibe Monotherapy
When ezetimibe is used alone, the following adverse reactions occur in ≥2% of patients and at rates greater than placebo: 1
- Upper respiratory tract infection 2, 3, 1
- Diarrhea 2, 3, 1
- Arthralgia (joint pain) 2, 3, 1
- Sinusitis 2, 3, 1
- Pain in extremities 2, 3, 1
- Fatigue 1
- Influenza 1
Ezetimibe Combined with Statins
When coadministered with a statin (incidence ≥2% and greater than statin alone), the most common adverse reactions shift slightly: 1
- Nasopharyngitis 2, 3, 1
- Myalgia (muscle pain) 2, 3, 1
- Upper respiratory tract infection 2, 1
- Arthralgia 2, 1
- Diarrhea 2, 1
- Back pain 1
- Influenza 1
- Pain in extremity 1
- Fatigue 1
Important Safety Context
The overall incidence of side effects with ezetimibe is similar to placebo, whether used as monotherapy or in combination with statins. 4, 2 This favorable safety profile has been consistently demonstrated across multiple large cardiovascular outcomes trials. 2
Serious but Rare Adverse Effects
While uncommon, clinicians should be aware of these potentially serious complications: 3, 1
- Myopathy and rhabdomyolysis (both as monotherapy and with statins) 3, 5, 1
- Elevated hepatic transaminases (particularly when combined with statins) 3, 1
The FDA label specifically warns that myopathy and rhabdomyolysis may occur with ezetimibe, and most post-marketing reports involved patients taking concomitant statins or fibrates. 1
Clinical Monitoring Recommendations
- Monitor for muscle symptoms including muscle pain, weakness, or twitching 5
- Perform liver enzyme testing as clinically indicated, and consider withdrawal if ALT or AST elevations ≥3 times the upper limit of normal persist 1
- Consider baseline and follow-up creatine kinase measurements in high-risk patients 5
- If myopathy is suspected, discontinue ezetimibe and other concomitant medications as appropriate 1
Common Pitfalls to Avoid
Do not attribute all muscle symptoms to ezetimibe without investigation. The 2022 BMJ guideline emphasizes that for patients experiencing muscle-related discomfort, clinicians should not attribute this to the medication or nocebo effect without careful case-by-case investigation. 4
Ezetimibe does not cause bleeding complications, hemorrhagic stroke, cancer, or noncardiovascular mortality based on large trials like IMPROVE-IT and SHARP. 2 If such complications arise, investigate other causes rather than attributing them to ezetimibe.