What are the side effects of ezetimibe (cholesterol-lowering medication)?

Ezetimibe Side Effects

Ezetimibe commonly causes upper respiratory tract infections, diarrhea, arthralgia, sinusitis, extremity pain, flu-like symptoms, and fatigue, with more serious but rare side effects including liver enzyme elevations and myopathy, especially when combined with statins. 1, 2

Common Side Effects

Ezetimibe monotherapy is generally well-tolerated, with a side effect profile similar to placebo in most clinical trials. The most frequently reported adverse effects include:

• Upper respiratory tract infection
• Diarrhea
• Arthralgia (joint pain)
• Sinusitis
• Pain in extremities
• Flu-like symptoms
• Fatigue 1, 2

When combined with statins, additional common side effects may include:

• Nasopharyngitis
• Myalgia
• Back pain 1

Serious Side Effects

Liver-Related Adverse Effects

• Elevated liver enzymes: Transaminase elevations may occur, particularly when ezetimibe is combined with statins 3, 1
• Baseline liver function tests are recommended before starting therapy
• Regular monitoring of liver function is advised, especially with concomitant statin therapy 1
• Ezetimibe should be avoided in moderate to severe hepatic disease 1

Muscle-Related Adverse Effects

• Myopathy and rhabdomyolysis: Though rare, these can occur, particularly with concomitant statin therapy 1, 2
• Risk factors include:
  • Concomitant statin use
  • Advanced age
  • Pre-existing muscle conditions 1
• Patients should report unexplained muscle pain, tenderness, weakness, fatigue, or fever immediately 2

Drug Interactions

Ezetimibe has relatively few drug interactions, but important ones to note include:

• Cyclosporine: May increase ezetimibe levels 1, 2
• Fibrates: May increase the bioavailability of ezetimibe 1, 2
• Bile acid sequestrants: Should be taken at least 2 hours before or 4 hours after ezetimibe 1, 2
• Statins: Combination increases risk of myopathy and hepatic effects, though generally safe when monitored 1

Special Populations

Renal Impairment

• No dosage adjustment needed in mild renal insufficiency
• Caution advised in moderate to severe renal impairment 1

Elderly

• Appears safe without dosage adjustments
• Increased monitoring may be warranted due to age-related physiological changes 1

Pregnancy and Lactation

• Limited safety data available
• Should be avoided during pregnancy and nursing unless benefits clearly outweigh risks 1, 2

Pediatric Use

• Generally safe and well-tolerated in pediatric populations with familial hypercholesterolemia 3, 1

Monitoring Recommendations

1. Baseline assessment: Liver function tests before initiating therapy 1
2. Regular monitoring: Periodic liver function tests, especially with statin co-therapy 1
3. Symptom vigilance: Instruct patients to report muscle symptoms promptly 2
4. Lipid profile: Regular monitoring to assess efficacy 1

Clinical Pearls

• Ezetimibe is generally well-tolerated as monotherapy with a safety profile similar to placebo 4
• The combination of ezetimibe with statins provides additional LDL-cholesterol lowering without substantially increasing adverse effects 3
• Ezetimibe may be a safe alternative for hyperlipidemic patients who are intolerant to statins 4
• Long-term safety data and outcome studies are still accumulating 4