What are the side effects of Zetia (ezetimibe)?

Side Effects of Zetia (Ezetimibe)

Zetia (ezetimibe) is generally well-tolerated with a side effect profile similar to placebo, with the most common adverse effects being upper respiratory tract infections, diarrhea, joint pain, sinusitis, and pain in extremities. 1

Common Side Effects

When Used as Monotherapy

• Upper respiratory tract infection is the most frequently reported adverse effect 2, 1
• Diarrhea occurs commonly in patients taking ezetimibe alone 2, 3
• Arthralgia (joint pain) is a common musculoskeletal complaint 2, 3, 1
• Sinusitis and inflammation of the sinuses are reported 3, 1
• Pain in extremities affects some patients 2, 3, 1
• Flu-like symptoms including general malaise 1
• Fatigue or feeling tired 4, 1

When Combined with Statins

• Nasopharyngitis (runny nose, sore throat) is the most common side effect in combination therapy 2, 1
• Myalgia (muscle pain) occurs more frequently when combined with statins 2, 5, 1
• Upper respiratory tract infection remains common 1
• Arthralgia continues to be reported 1
• Diarrhea persists as a gastrointestinal complaint 2, 1
• Back pain is noted in combination therapy 1

Serious but Rare Adverse Effects

Muscle-Related Complications

Myopathy and rhabdomyolysis can occur with ezetimibe, both as monotherapy and when combined with statins, though these are rare. 2, 5, 1

• Cases of muscle breakdown (rhabdomyolysis) have been reported 2, 1
• Patients should report unexplained muscle pain, tenderness, weakness, or unusual fatigue immediately 5, 1
• The risk increases when ezetimibe is combined with statins or fibrates 5, 1
• Consider baseline and follow-up creatine kinase measurements in high-risk patients 5

Hepatic Effects

• Elevated liver transaminases can occur, particularly when combined with statins 2, 3, 1
• Your healthcare provider should perform blood tests to monitor liver function before and during treatment 1
• Ezetimibe should not be used in patients with moderate to severe hepatic impairment 2

Allergic Reactions

Stop ezetimibe immediately and seek emergency care if you experience signs of a serious allergic reaction: 1

• Swelling of the face, tongue, or throat 1
• Difficulty breathing or swallowing 1
• Fainting or feeling dizzy 1
• Very fast heartbeat 1
• Severe skin rash, hives, and itching 1

Important Safety Considerations

Overall Safety Profile

• The overall incidence of side effects is similar to placebo in clinical trials 4, 6, 7, 8
• Adverse reactions are generally mild and transient 4
• Ezetimibe has minimal systemic absorption, resulting in few drug interactions 8

Special Populations

• All lipid-lowering drugs, including ezetimibe, should be avoided during pregnancy and nursing or in women who may become pregnant 4
• It is unknown if ezetimibe passes into breast milk 1

Monitoring Recommendations

• Regular blood samples or visits after starting ezetimibe are encouraged to monitor adherence and potential harms 4
• Your healthcare provider may check LDL-C levels as early as 4 weeks after starting treatment 1

What Ezetimibe Does NOT Cause

Importantly, major guidelines confirm that ezetimibe does not increase risk of: 2

• Hemorrhagic stroke 2
• Cancer 2
• Noncardiovascular mortality 2
• Bleeding-related adverse events 2
• Pulmonary toxicity or interstitial lung disease 3
• Oral health complications such as gingivitis 2

Practical Considerations

• Ezetimibe is taken as 10 mg orally once daily, with or without food 2, 1
• Most people need to take this medication for the rest of their lives 4
• The medication has no or little effect on body weight 4
• If taking a bile acid sequestrant, take ezetimibe at least 2 hours before or 4 hours after the bile acid sequestrant 1