II. Indications
- Hyperlipidemia monotherapy
-
Hyperlipidemia combination therapy
- Adjunct to Statin agents in multi-drug regimen
- Homozygous Sitosterolemia
III. Contraindications
- Active liver disease (when used in combination with a Statin)
- Gemfibrozil concurrent use
IV. Mechanism: Cholesterol absorption inhibitor
- Class: 2-Azetidinone
- Selective Cholesterol absorption inhibitor
- Inhibits absorption at Small Intestine brush border
- Blocks Cholesterol absorption from diet and bile acids
- Effects
- Lowers LDL 18 to 25%
- Lowers Triglycerides 8%
- Raises HDL 1%
V. Medications
- Ezetimibe (Zetia)
- Combination Agents
- Vytorin: Simvastatin (Zocor) combined with Ezetimibe (Zetia)
- Liptruzet: Atorvastatin (Lipitor) combined with Ezetimibe (Zetia)
VI. Dosing: Adults (and Children over age 10 years)
- Ezetimibe 10 mg orally daily
VII. Adverse Effects
- Minimal adverse effects due to minimal absorption
- Provokes Statin-related myalgias and Arthralgias
VIII. Safety
- Pregnancy Category C
- Unknown safety in Lactation
IX. Drug Interactions
-
Warfarin
- Ezetimibe may increase Anticoagulation effect of Warfarin
-
Cyclosporine
- Both Ezetimibe and Cyclosporine levels increase when use together
-
Fibric Acid Derivative (e.g. Gemfibrozil, Fenofibrate)
- Increased risk of Cholelithiasis when combined with Ezetimibe
- Avoid combination use of Gemfibrozil with Ezetimibe
- Fenofibrate may be used with caution with Ezetimibe
-
Bile Acid Sequestrants
- Decreases Ezetimibe absorption
- Take Ezetimibe at least 2 hours before or at least 4 to 6 hours after Bile Acid Sequestrants
X. Efficacy
- IMPROVE-IT Trial
- NNT 50 for one less CV event in high risk patients taking Vytorin (10/40) instead of Simvastatin alone for 7 years
- (2015) Presc Lett 22(1): 2
- Enhance Study
- Found that Vytorin is not more effective than Simvastatin alone
- Despite LDL lowering, did not further slow atherosclerosis
- Casts doubt on Ezetimibe (Zetia) benefit, but further trials are needed
- Kastelein (2008) N Engl J Med 358:1431-43 [PubMed]
- Initial Data
- Triglyceride levels did not change significantly
- LDL Cholesterol reduced 17%
- HDL Cholesterol increased 1.3%
- Dujovne (2002) Am J Cardiol 90:1092-7 [PubMed]
- Postulated reason for lack of effect in coronary event prevention despite LDL lowering
- Scavenger Receptor B1 inhibition appears to be the mechanism for this lack of effect
- This inhibition results in HDL inhibition
XI. Resources
Images: Related links to external sites (from Bing)
Related Studies
| ezetimibe (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| EZETIMIBE 10 MG TABLET | Generic | $0.09 each |
| EZETIMIBE-SIMVASTATIN 10-10 MG | Generic | $0.52 each |
| EZETIMIBE-SIMVASTATIN 10-20 MG | Generic | $0.59 each |
| EZETIMIBE-SIMVASTATIN 10-40 MG | Generic | $0.43 each |
| EZETIMIBE-SIMVASTATIN 10-80 MG | Generic | $0.56 each |
| zetia (on 1/14/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| ZETIA 10 MG TABLET | Generic | $0.09 each |
| vytorin (on 8/17/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| VYTORIN 10-40 MG TABLET | Generic | $0.43 each |