Zetia (Last Updated - 5/19/2003)
-Generic Name - Ezetimibe
-Trade Name - Zetia
-Manufacturer - Merck
-Drug Class - dietary and biliary cholesterol absorption inhibitor
-Drug Structure - azetidione-based (1)
-Bioavailability -
-% Protein Bound -
-Half Life - 22 hours for active metabolite – good for qd dosing (1)
-Metabolism / Excretion - undergoes glucuronidation to active metabolite in small intestine, active metabolite absorbed
   and excreted into bile by liver for excretion in stool (1)
-Mechanism - blocks small intestinal brush-border absorption of dietary and biliary cholesterol, lowering plasma total
   cholesterol and LDL (1)
-Clinical Effects - lowers LDL by 19% - equivalent to 3 doublings of simvastatin (Zocor) from baseline dose (each
   doubling of simvastatin (Zocor) dose provides additional 6% lowering of LDL) (1)
      -Primary Hypercholesterolemia:
         -monotherapy - lowers LDL by 17%, trigs by 6% and raises HDL by 1.3% (2)
         -combo - when given w/ simvastatin (Zocor) 20 mg (normal starting dose or low-dose simvastatin) lowers LDL by
            52% - equivalent to 80 mg of simvastatin (Zocor) alone - benefit b/c lesser chance of myopathy with starting
            or low-dose statins (1)
               -when given w/ simvastatin (Zocor) 10 mg qd - lowers LDL by 44% (compared to 27% w/ simvastatin (Zocor)
                  10 mg qd alone) (2)
               -when given w/ simvastatin (Zocor) 20 mg qd - lowers LDL by 45% (compared to 36% w/ simvastatin (Zocor)
                  20 mg qd alone) (2)
               -when given w/ simvastatin (Zocor) 40 mg qd - lowers LDL by 53% (compared to 36% w/ simvastatin (Zocor)
                  40 mg qd alone) (2)
               -when given w/ simvastatin (Zocor) 80 mg qd - lowers LDL by 57% (compared to 44% w/ simvastatin (Zocor)
                  80 mg qd alone) (2)
-Clinical Uses - monotherapy or in combo with statins (can be taken simultaneously) (2)
-Toxicities / Adverse Effects - elevated transaminases (> 3x upper limit of normal) – more common when given w/ statin (2)
-Contraindications - hepatic insufficiency(2)
-Dosing and Administration - 10 mg po qd (1)
-Cost - $2.36 / day ($70.80 / 30 days) (2)
-Drug Interactions:
   -increased bile cholesterol concentration – predisposes to gallbladder disease (2)
   -bile acid sequestrants (cholestyramine and colestipol) interfere w/ absorption of active metabolite – take ezetimibe at
      least 2 hours before or 4 hours after bile acid sequestrants (2)
   -Cyclosporine – increases plasma levels (2)

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References:

1) Mahley, Robert W. and Bersot, Thomas P. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics – 10th
   Edition. 2001. Chapter 36 p. 995.
2) The Medical Letter. Vol. 45 (Issue 1151). March 3, 2003. p. 17-19.