Ezetimibe selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein in the brush border of the small intestine. This action:

1. Reduces Cholesterol Absorption: Blocks dietary and biliary cholesterol uptake, decreasing delivery to the liver.
2. Enhances LDL Clearance: Depletes hepatic cholesterol stores, prompting upregulation of LDL receptors and increased clearance of LDL particles from the bloodstream.
3. Synergistic Effect with Statins: Combined use with statins targets both cholesterol absorption and synthesis (Lippincott Textbook of Pharmacology).

1. Primary Hypercholesterolemia:
   • Monotherapy or adjunct to statins for LDL cholesterol reduction in patients with primary hyperlipidemia.
2. Homozygous Familial Hypercholesterolemia (HoFH):
   • Adjunctive therapy to statins and other lipid-lowering treatments.
3. Sitosterolemia:
   • Reduces elevated plant sterol levels in this rare genetic disorder (BNF).
4. Cardiovascular Risk Reduction:
   • Combined with simvastatin in high-risk patients (e.g., post-acute coronary syndrome) to reduce cardiovascular events (Lange Basic & Clinical Pharmacology).

• Adults:
  • Monotherapy or Combination: 10 mg orally once daily, with or without food.
  • Renal/Hepatic Impairment: No dose adjustment required, but use caution in moderate-to-severe hepatic dysfunction.
• Pediatrics:
  • Ages 10–17: 10 mg daily for heterozygous familial hypercholesterolemia.

Key Considerations:

• Administer 2 hours before or 4 hours after bile acid sequestrants (e.g., cholestyramine) to avoid reduced absorption.
• Available as a fixed-dose combination with simvastatin (e.g., Vytorin: 10 mg ezetimibe + 10–80 mg simvastatin).

• Common (≥1%):
  • Gastrointestinal disturbances (diarrhea, abdominal pain, flatulence).
  • Fatigue, headache, or muscle pain (less frequent than with statins).
• Serious (Rare):
  • Hepatotoxicity: Elevated transaminases (discontinue if persistent).
  • Hypersensitivity Reactions: Rash, angioedema.
  • Myopathy: Rare, but risk increases with concomitant statins.

• Contraindications:
  • Hypersensitivity to ezetimibe.
  • Active liver disease or unexplained persistent LFT abnormalities.
• Pregnancy/Lactation:
  • Pregnancy Category C: Avoid unless benefits outweigh risks; discontinue during breastfeeding.
• Monitoring:
  • Liver Function Tests (LFTs): Baseline and periodically during treatment.

Lipid Profile: Assess efficacy after 2–4 weeks

1. Cyclosporine: ↑ Ezetimibe exposure (contraindicated due to risk of toxicity).
2. Fibrates (e.g., fenofibrate): May ↑ cholesterol excretion into bile, increasing gallstone risk.
3. Bile Acid Sequestrants: ↓ Ezetimibe absorption (administer 2–4 hours apart).
4. Statins: Synergistic lipid-lowering effect; monitor for myopathy (BNF).

• Generic Name: Ezetimibe.
• Brand Names: Zetia (monotherapy), Vytorin (combination with simvastatin).