Ezetimibe
Mechanism :
Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors.
Indication :
- Homozygous Familial Hypercholesterolemia
- Homozygous Sitosterolemia
- Primary Hyperlipidemia
Contraindications :
Hypersensitivity, Caution if hepatic impairment.
Dosing :
Under 10 years:
Safety and efficacy not established.
Above 10 years:
10 mg orally once every day in combination with
atorvastatin or
simvastatin, adjunctive diet and in combination with H mg-CoA reductase inhibitors.
Adverse Effect :
Abdominal pain, diarrhea, joint pain, muscle aches, back pain, and sinusitis, hypersensitivity reactions, nausea, myopathy or rhabdomyolysis, pancreatitis, hepatitis
Interaction :
Cholestyramine (Questran), Colestipol (Colestid) and Colesevelam (WelChol), Bile Acid-Binding Drugs: may be used to treat elevated levels of cholesterol, bind to ezetimibe and reduce its absorption from the intestine by about 50%. Therefore, ezetimibe should be taken at least two hours before or 4 hours after administration of these drugs.
Cyclosporine (Gengraf, Neoral): Increases the levels of ezetimibe while ezetimibe increases levels of cyclosporine. Combining both drugs may increase side effects of either drug.
Warfarin: If ezetimibe is added to warfarin, a coumarin anticoagulant, the International Normalized Ratio (INR) should be appropriately monitored.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in normal renal function |
| HD | Unlikely to be dialysed. Dose as in normal renal function |
| HDF/High flux | Unlikely to be dialysed. Dose as in normal renal function |
| CAV/VVHD | Unlikely to be dialysed. Dose as in normal renal function |
Hepatic Dose :
Mild hepatic impairment: No dosage adjustment needed.
Moderate and severe hepatic impairment: Due to insufficient data, the manufacturer does not recommend use of this drug in these patients.