What are the side effects of Zetia (ezetimibe)?

Side Effects of Ezetimibe (Zetia)

Ezetimibe (Zetia) is generally well tolerated with a favorable side effect profile compared to many other lipid-lowering medications, with the most common adverse effects being upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities when used as monotherapy. 1

Common Side Effects

When used alone (monotherapy), ezetimibe may cause:

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

When used in combination with statins, additional common side effects include:

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

Serious Side Effects

Liver-Related Concerns

• Hepatic transaminase elevations: Persistent elevations may occur, particularly with concomitant statin therapy 1
• Serious hepatotoxicity: Rare cases of serious drug-induced liver disease have been reported 3
• Not recommended in patients with moderate to severe hepatic impairment 1

Muscle-Related Concerns

• Myopathy and rhabdomyolysis: Cases have been reported when ezetimibe is used alone or in combination with statins 1, 2
• Risk factors include:
  • Concomitant use with statins
  • Advanced age
  • Pre-existing muscle conditions

Monitoring Recommendations

1. Liver function: Monitor hepatic transaminases before and during treatment, particularly when used with statins 1
2. Muscle symptoms: Promptly evaluate unexplained muscle pain, tenderness, weakness, fatigue, or fever 2
3. Follow-up: Regular monitoring is recommended, especially during the initial treatment period

Drug Interactions

Ezetimibe has a relatively favorable drug interaction profile 4, but important interactions include:

• Cyclosporine: May increase ezetimibe exposure; use with caution and monitor cyclosporine levels 1, 4
• Fibrates: May increase ezetimibe bioavailability 1, 4
• Bile acid sequestrants: Reduce ezetimibe absorption; administer ezetimibe at least 2 hours before or 4 hours after bile acid sequestrants 1, 2

Special Populations

• Pregnancy/Lactation: No safety data in humans; avoid use 1
• Renal impairment: No dosage adjustment necessary in mild-to-severe renal insufficiency 4
• Hepatic impairment: No dosage adjustment needed in mild hepatic impairment, but not recommended in moderate to severe hepatic impairment 1

Clinical Pearls

• Ezetimibe can be taken with or without food, at any time of day 2
• The standard dose is 10 mg orally once daily 1
• Unlike bile acid sequestrants, ezetimibe does not typically worsen hypertriglyceridemia 5
• Ezetimibe has a long half-life (approximately 22 hours), allowing for once-daily dosing 4
• The side effect profile is similar to placebo in many clinical trials 5, 6

When to Discontinue

Consider discontinuation if:

• Significant, persistent elevations in liver enzymes occur
• Severe muscle symptoms develop, especially with elevated creatine kinase
• Serious hypersensitivity reactions occur

While ezetimibe is generally well tolerated, clinicians should remain vigilant for potential adverse effects, particularly when used in combination with statins or in patients with pre-existing liver conditions.