RxPRODUCT NEWS PROFILE: Vytorin (ezetimibe/simvastatin)

The leading cause of death for both men and women for decades, coronary artery disease affects almost 13 million Americans and kills approximately 1 million from complications each year. Recent studies have promoted lower low-density lipoprotein cholesterol (LDL-C) levels, because many trials have documented reduced rates of complications (eg, stroke; see Table¹). Media attention has been extensive, and experts are recommending assertive pharmacologic treatment of hyperlipidemia.²

Patients with primary hypercholesterolemia despite diet and lifestyle changes may be turning to Merck/Schering-Plough's newly approved Vytorin (ezetimibe/simvastatin) to reduce serum LDL-C levels. The FDA approved Vytorin as the first combination product to decrease cholesterol. Vytorin exerts its antilipidemic effect through 2 different mechanisms: the ezetimibe component prevents intestinal absorption of dietary and biliary cholesterol, while the simvastatin component inhibits hepatic cholesterol production. Both agents are currently available individually for the treatment of hyperlipidemia. Vytorin, however, strategically combines therapies in a single dosage unit to decrease LDL-C more effectively than monotherapy while promoting patient compliance.³

Clinical Trials

Three major studies examined the efficacy of ezetimibe and simvastatin in combination, especially when compared with antihyperlipidemic monotherapy.

A 12-week multicenter, double-blind placebo-controlled clinical study of 1528 patients compared the use of Vytorin with the use of simvastatin alone. At the recommended starting dose of 10/20 mg, the Vytorin-treated patients experienced a 52% decrease in LDL-C, while patients treated with simvastatin 20 mg experienced an LDL-C reduction of 34% and those taking simvastatin 40 mg had a 41% reduction. As the dose of Vytorin increased, so did the percentage decrease in LDL-C: patients taking the 10/40-mg strength experienced an average 55% decrease, and those taking the maximum dose of 10/80 mg experienced a 60% decrease.³

A 24-week, multicenter, randomized, double-blind, active controlled study of 788 patients compared the use of Vytorin with the use of atorvastatin alone. At their starting doses, both agents caused a statistically significant decrease in LDL cholesterol: 50% with Vytorin 10/20 mg, 37% with atorvastatin 10 mg, and 44% with atorvastatin 20 mg.⁴

A phase 3 multicenter, randomized, double-blind controlled study of 710 patients compared the use of Vytorin with the use of simvastatin in achieving a goal serum LDL-C level of <100 mg/dL. In the Vytorin 10/20-mg group, 83% reached goal LDL-C levels, whereas 46% of simvastatin patients achieved goal levels.⁵

Safety

Liver function tests should be given prior to initiating Vytorin therapy and periodically during treatment. Additionally, patients taking 10/80-mg Vytorin should have liver function tests done every 3 months throughout the first year of therapy. Vytorin should be limited to 10/10 mg daily when administered concurrently with cyclosporine and to 10/20 mg daily when co-administered with amiodarone or verapamil. Coadministration with fibrates has not been studied and is not recommended.³

Pharmacists should advise patients to take Vytorin in the evening or at bedtime. It may be taken with or without food. Patients must report muscle pain or weakness immediately to a health care provider. Vytorin is contraindicated during pregnancy or breastfeeding. Commonly reported side effects include headache, upper respiratory tract infection, myalgia, influenza, and extremity pain.³

Availability

Vytorin will be available in the following strengths: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg. (The ezetimibe portion will remain constant at 10 mg, and the simvastatin portion will vary.) The starting dose will be 10/20 mg, except for patients requiring an LDL-C reduction of >55%, in which case the starting dose may be 10/40 mg.³

Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health. Dr. Holmberg is a pharmacist with Phoenix Indian Medical Center, Phoenix, Ariz. The opinions expressed are those of the authors and not necessarily of any government agency.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.