brand logo

Am Fam Physician. 2005;72(10):2081-2082


Ezetimibe/simvastatin (Vytorin) is a combination of ezetimibe (Zetia), which inhibits the absorption of cholesterol by the small intestine, and simvastatin (Zocor), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, or statin. Ezetimibe/simvastatin, in conjunction with diet changes, is indicated for patients with hypercholesterolemia.1

NameStarting dosageDose formApproximate monthly cost*
Ezetimibe/simvastatin (Vytorin)10/20 mg daily10/10-mg, 10/20-mg, 10/40-mg, and 10/80-mg tablets$80


Adverse reactions to ezetimibe/simvastatin include elevated transaminase levels, myopathy, and rhabdomyolysis; they are related to the dose of simvastatin and almost always are reversible.1 Myopathy and rhabdomyolysis are the most serious known adverse reactions to statins. In clinical trials of the combination, rhabdomyolysis did not occur16 and there was only one reported occurrence of myopathy,4 which resolved after discontinuation. The rate of myopathy was approximately one per 2,800 persons.26 Elevation of liver enzymes to more than three times the normal level occurred in 1.7 percent of patients receiving ezetimibe/simvastatin.1 The product labeling for simvastatin states that in clinical trials, elevated liver function occurred in 1 percent of patients.7

Simvastatin serum levels may be increased when simvastatin is given concomitantly with medications that affect the cytochrome P450 (CYP450) 3A4 enzyme system, increasing the risk of myopathy and rhabdomyolysis. To avoid this risk, physicians may consider temporarily discontinuing ezetimibe/simvastatin for the duration of therapy with macrolide antibiotics and azole antifungals. Ezetimibe does not interact with drugs metabolized by the CYP450 system. It is pregnancy category X and must not be given to women who may be pregnant.1


Ezetimibe/simvastatin generally is well tolerated. The addition of ezetimibe to simvastatin did not affect tolerability over 40 weeks’ administration; no study has assessed ezetimibe/simvastatin for a longer duration.5 Adverse effects of ezetimibe/ simvastatin are similar to those of statin monotherapy.15 Headache, upper respiratory infection, influenza, myalgia, and pain in extremities were the only adverse effects more common than with placebo, and these occurred in less than 4 percent of patients receiving ezetimibe/simvastatin.1


Two studies,3,5 with a total of 1,555 participants, demonstrated ezetimibe/simvastatin to be more effective in lowering low-density lipoprotein (LDL) cholesterol levels than simvastatin monotherapy, with a mean reduction of 51 to 53 percent compared with 37 to 39 percent with simvastatin alone. Another two studies,2,6 with a total of 2,690 participants, showed ezetimibe/simvastatin to be more effective than atorvastatin (Lipitor) in lowering LDL cholesterol, resulting in an average reduction of 52 to 53 percent compared with 45 percent in both studies with atorvastatin alone. No studies of ezetimibe alone or the combination of ezetimibe and simvastatin have examined cardiovascular morbidity or mortality or all-cause mortality.


The price of ezetimibe/simvastatin (approximately $80 per month for all doses) is generally lower than that of other statins. Generic lovastatin costs less ($30 to $60 per month). The ezetimibe/simvastatin combination is more cost-effective than taking ezetimibe and a statin separately.


The recommended starting dosage for ezetimibe/simvastatin is 10 mg ezetimibe and 20 mg simvastatin daily in the evening, taken with or without food. Patients who need a smaller reduction in LDL cholesterol levels can start with a dosage of 10/10 mg daily, and those requiring a larger reduction in LDL levels (greater than 55 percent) may start with a dosage of 10/40 mg daily. No dosage adjustments are necessary in older patients, those with mild hepatic insufficiency, or those with mild to moderate renal insufficiency.1

Bottom Line

Low doses of ezetimibe/simvastatin provide greater improvements in lipid profile than simvastatin or atorvastatin monotherapy. Ezetimibe/simvastatin may be useful in patients who are unable to tolerate high-dose statin therapy. Combination ezetimibe-simvastatin is less expensive than adding ezetimibe to a statin and more convenient than taking two separate medicines. No trials have been performed to determine the effect of ezetimibe/simvastatin on stroke, myocardial infarction, or mortality rate.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

This series is coordinated by Allen F. Shaughnessy, PharmD, assistant medical editor.

A collection of STEPS published in AFP is available at

Continue Reading

More in AFP

More in PubMed

Copyright © 2005 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.