Can ezetimibe (Zetia) cause transaminitis (elevated liver enzymes)?

Does Ezetimibe (Zetia) Cause Transaminitis?

Ezetimibe (Zetia) can cause transaminitis (elevated liver enzymes), particularly when used in combination with statins, but this effect is uncommon when used as monotherapy. 1

Liver Effects of Ezetimibe

Monotherapy

• When used alone, ezetimibe has a low risk of causing significant liver enzyme elevations
• The FDA drug label does not list transaminitis as a common adverse effect when ezetimibe is used as monotherapy 1
• Post-marketing surveillance has reported elevations in liver transaminases, including elevations more than 5 times the upper limit of normal (ULN) 1

Combination Therapy

• The incidence of consecutive increased transaminases (≥3 X ULN) was higher in patients receiving ezetimibe administered with statins (1.3%) than in patients treated with statins alone (0.4%) 1
• When combined with fenofibrate, clinically important elevations in hepatic transaminase levels were observed in 2.7% of patients 1

Monitoring Recommendations

The American College of Cardiology (ACC) provides specific guidance regarding liver monitoring with ezetimibe:

1. Baseline Testing: Obtain liver function tests before initiating therapy 2

2. Ongoing Monitoring:

   • Monitor hepatic transaminases during treatment based on monitoring recommendations for statin therapy if ezetimibe is used in combination with a statin 2, 1
   • Consider withdrawal of ezetimibe if increases in ALT or AST ≥3 X ULN persist 1

3. Special Populations:

   • Ezetimibe is not recommended in patients with moderate/severe hepatic impairment 2, 3
   • Use caution in patients with pre-existing liver disease 1

Risk Factors for Ezetimibe-Related Transaminitis

Several factors may increase the risk of transaminitis with ezetimibe:

• Concomitant use with statins 1
• Pre-existing liver disease 1
• Moderate to severe hepatic impairment 2, 3
• Use with other medications known to affect liver function

Clinical Implications

While rare, there have been case reports of severe hepatic side effects with ezetimibe, including:

• Cholestatic hepatitis 4
• Acute autoimmune hepatitis 4

However, these severe reactions appear to be extremely rare, and the overall safety profile of ezetimibe regarding liver function is favorable 5.

Practical Recommendations

1. Before Starting Ezetimibe:

   • Assess baseline liver function
   • Consider alternative agents in patients with moderate to severe liver disease

2. During Treatment:

   • Monitor liver enzymes periodically, especially when combined with statins
   • Educate patients about symptoms of liver dysfunction (jaundice, right upper quadrant pain, fatigue, nausea)
   • Consider more frequent monitoring in patients with risk factors for liver disease

3. If Transaminitis Occurs:

   • For mild elevations (<3x ULN): Continue monitoring
   • For persistent elevations ≥3x ULN: Consider discontinuing ezetimibe 1
   • For severe elevations or symptoms: Discontinue immediately

Conclusion

While ezetimibe can cause transaminitis, particularly when used with statins, this effect is relatively uncommon and rarely leads to serious clinical consequences when appropriate monitoring is implemented. The benefits of ezetimibe in cholesterol management typically outweigh this risk for most patients.