Ezetimibe Tablets

Mechanism

Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients. The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed on enterocytes/gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin. Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPC1L1 and forms a NPC1L1/cholesterol complex. The complex is then internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.

Pharmacodynamics

It reduces total cholesterol and LDL cholesterol levels without significantly affecting triglycerides, leading to improved lipid profile and cardiovascular protection.

Pharamcokinetics

• Absorption: Rapidly absorbed and converted to active glucuronide
• Bioavailability: Moderate (variable)
• Peak Plasma Time: 1–2 hours (parent drug), 4–12 hours (active metabolite)
• Protein Binding: >90%
• Metabolism: Hepatic and intestinal glucuronidation
• Half-life: ~22 hours
• Excretion: Feces (~78%), urine (~11%)

Side Effects

• Headache
• Abdominal pain
• Diarrhea
• Fatigue
• Elevated liver enzymes (with statins)

Contraindication

• Active liver disease (with statins)
• Hypersensitivity to ezetimibe

Interaction

• Cyclosporine
• Bile acid sequestrants (reduced absorption)
• Anticoagulants
• Statins (monitor liver enzymes)

Warning and Precautions

• Monitor liver function when used with statins
• Use cautiously in hepatic impairment
• Regular lipid monitoring required
• Not recommended in moderate to severe liver disease
• Not recommended during pregnancy or breastfeeding; use only if benefit outweighs risk under medical supervision.

Dosage

As directed by the Physician.