Pharm

Ezetimibe

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Ezetimibe, Zetia, Vytorin, Liptruzet

  • Indications
  1. Hyperlipidemia monotherapy
  2. Hyperlipidemia combination therapy
    1. Adjunct to Statin agents in multi-drug regimen
  3. Homozygous Sitosterolemia
  • Contraindications
  1. Active liver disease (when used in combination with a Statin)
  2. Gemfibrozil concurrent use
  1. Class: 2-Azetidinone
  2. Selective Cholesterol absorption inhibitor
    1. Inhibits absorption at Small Intestine brush border
    2. Blocks Cholesterol absorption from diet and bile acids
  3. Effects
    1. Lowers LDL 18 to 25%
    2. Lowers Triglycerides 8%
    3. Raises HDL 1%
  • Medications
  1. Ezetimibe (Zetia)
  2. Combination Agents
    1. Vytorin: Simvastatin (Zocor) combined with Ezetimibe (Zetia)
    2. Liptruzet: Atorvastatin (Lipitor) combined with Ezetimibe (Zetia)
  • Dosing
  • Adults (and Children over age 10 years)
  1. Ezetimibe 10 mg orally daily
  • Adverse Effects
  1. Minimal adverse effects due to minimal absorption
  2. Provokes Statin-related myalgias and Arthralgias
  • Safety
  1. Pregnancy Category C
  2. Unknown safety in Lactation
  • Drug Interactions
  1. Warfarin
    1. Ezetimibe may increase Anticoagulation effect of Warfarin
  2. Cyclosporine
    1. Both Ezetimibe and Cyclosporine levels increase when use together
  3. Fibric Acid Derivative (e.g. Gemfibrozil, Fenofibrate)
    1. Increased risk of Cholelithiasis when combined with Ezetimibe
    2. Avoid combination use of Gemfibrozil with Ezetimibe
    3. Fenofibrate may be used with caution with Ezetimibe
  4. Bile Acid Sequestrants
    1. Decreases Ezetimibe absorption
    2. Take Ezetimibe at least 2 hours before or at least 4 to 6 hours after Bile Acid Sequestrants
  • Efficacy
  1. IMPROVE-IT Trial
    1. NNT 50 for one less CV event in high risk patients taking Vytorin (10/40) instead of Simvastatin alone for 7 years
    2. (2015) Presc Lett 22(1): 2
  2. Enhance Study
    1. Found that Vytorin is not more effective than Simvastatin alone
    2. Despite LDL lowering, did not further slow atherosclerosis
    3. Casts doubt on Ezetimibe (Zetia) benefit, but further trials are needed
    4. Kastelein (2008) N Engl J Med 358:1431-43 [PubMed]
  3. Initial Data
    1. Triglyceride levels did not change significantly
    2. LDL Cholesterol reduced 17%
    3. HDL Cholesterol increased 1.3%
    4. Dujovne (2002) Am J Cardiol 90:1092-7 [PubMed]
  4. Postulated reason for lack of effect in coronary event prevention despite LDL lowering
    1. Scavenger Receptor B1 inhibition appears to be the mechanism for this lack of effect
    2. This inhibition results in HDL inhibition
  • Resources
  1. Ezetimibe (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=206d702c-b09a-4555-972b-6555d6d6d6e6
  • References
  1. (2022) Non-StatinLipid Lowering Agents, Presc Lett, #380202
  2. (2022) Med Lett Drug Ther 64(1659): 145-52