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Ezetimibe

From Pharmacopedia
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Summary
Common uses
Hyperlipidemia (alone or with a statin)0, Statin intolerance0, Familial hypercholesterolemia (combination)0, Post-ACS secondary prevention (with statin, per IMPROVE-IT)0
Pharmacy
Starting dose
10 mg PO once daily, with or without food
Preparations
10 mg tablet; also as fixed-dose combinations with simvastatin (Vytorin) and atorvastatin (Liptruzet, withdrawn US 2015 but generics exist)
US FDA Max
10 mg/d
Pharmacology
Routes
Oral
Onset
LDL lowering within 2 weeks
Duration
24 hours
Half-life
~22 hours (parent + active glucuronide)[1]
Bioavailability
Variable (oral; rapidly conjugated to active glucuronide; food does not affect)[1]
Pregnancy
Limited data; generally avoided particularly in combination with statin.[citation needed]
Legal status
Rx-only in US
Purported mechanism
Ezetimibe binds the Niemann-Pick C1-like 1 (NPC1L1) transporter on the apical brush border of small-intestinal enterocytes, blocking the absorption of cholesterol (both dietary and biliary) without inhibiting absorption of triglycerides, fatty acids, bile acids, or fat-soluble vitamins.0 Reduced enterohepatic cholesterol delivery raises LDL receptor expression and lowers circulating LDL ~15-20% on top of statin. The IMPROVE-IT trial (2015) established that ezetimibe added to simvastatin improves post-ACS cardiovascular outcomes, validating the "lower LDL = better" hypothesis with a non-statin agent[1].

References

  1. 1.0 1.1 1.2 FDA Prescribing Information, Zetia (ezetimibe), Merck/Schering, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021445s039lbl.pdf