What are the contraindications for Ezetimibe (cholesterol absorption inhibitor)?

Contraindications for Ezetimibe

The only absolute contraindication for ezetimibe is a history of hypersensitivity to the medication or any of its components. 1, 2

Understanding Ezetimibe

Ezetimibe is a cholesterol absorption inhibitor that works by:

• Inhibiting the NPC1L1 protein in the small intestine
• Reducing cholesterol absorption from the intestinal lumen
• Providing approximately 18% LDL-C reduction as monotherapy and an additional 25% reduction when combined with statins 1

Contraindications in Detail

Absolute Contraindication

• Known hypersensitivity to ezetimibe or any excipients in the formulation 2
  • Hypersensitivity reactions may include anaphylaxis, angioedema, rash, and urticaria

Relative Contraindications/Precautions

1. Hepatic Impairment

   • Not recommended in patients with moderate to severe hepatic impairment 1
   • Monitor liver function tests, especially when used with statins
   • Consider discontinuation if ALT or AST elevations ≥3 times upper limit of normal persist 2

2. Pregnancy and Lactation

   • No safety data in humans; avoid use during pregnancy and lactation 1
   • Should be discontinued when pregnancy is recognized unless benefits outweigh potential risks 2

3. Drug Interactions

   • Use with caution with:
     • Cyclosporine (may increase ezetimibe levels) 1, 3
     • Fibrates (may increase ezetimibe bioavailability) 1, 3
   • Administer at least 2 hours before or 4 hours after bile acid sequestrants 2, 3
   • Avoid concomitant use with statins in patients for whom statins are contraindicated 2

Special Considerations

Myopathy Risk

• Cases of myopathy and rhabdomyolysis have been reported with ezetimibe alone or in combination with statins 1
• Risk increases when combined with statins or other agents known to cause myopathy 2
• Consider discontinuation if unexplained muscle pain, tenderness, or weakness occurs 2

Monitoring Recommendations

• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating therapy 2
• Monitor liver enzymes before and during treatment, especially when combined with statins 1
• In clinical trials, the incidence of consecutive elevations (≥3 X ULN) in hepatic transaminases was 1.3% for patients treated with ezetimibe administered with statins compared to 0.4% for patients treated with statins alone 2

Clinical Application Algorithm

1. Before prescribing ezetimibe:

   • Screen for history of hypersensitivity to ezetimibe
   • Assess liver function
   • Review current medications for potential interactions
   • Determine pregnancy status in women of childbearing potential

2. Do not prescribe ezetimibe if:

   • Patient has known hypersensitivity to ezetimibe
   • Patient has moderate to severe hepatic impairment
   • Patient is pregnant or breastfeeding (unless benefits clearly outweigh risks)

3. Use with caution in patients:

   • Taking cyclosporine or fibrates
   • With history of muscle disorders
   • With mild hepatic impairment

4. Monitoring after initiation:

   • Assess LDL-C response after 4-8 weeks
   • Monitor for signs of myopathy or liver dysfunction
   • Discontinue if persistent liver enzyme elevations or muscle symptoms occur

By following these guidelines, clinicians can safely prescribe ezetimibe while minimizing risks associated with its use.