Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

GENERIC NAME: ezetimibe/simvastatin

BRAND NAME: Vytorin

DRUG CLASS AND MECHANISM:  Vytorin is a combination of ezetimibe (Zetia) and simvastatin (Zocor) that is used for treating high levels of cholesterol in the blood. Vytorin reduces total cholesterol and low density lipoprotein (LDL or "bad") cholesterol while it increases high density lipoprotein (HDL or "good") cholesterol. The ezetimibe component of Vytorin lowers blood cholesterol by blocking the absorption of cholesterol, including dietary cholesterol, from the intestine. It does not affect the absorption of triglycerides. The simvastatin component of Vytorin belongs to a class of drugs called HMG-CoA reductase inhibitors, commonly called "statins." Statins reduce cholesterol by blocking an enzyme in the liver (HMG-CoA reductase) that produces cholesterol. Statins lower total and LDL cholesterol in the blood as well as triglycerides. They also increase HDL cholesterol.

LDL cholesterol is believed to be an important cause of coronary artery disease. Lowering LDL cholesterol levels slows and may even reverse coronary artery disease. Raising HDL cholesterol levels also may slow coronary artery disease. The FDA approved Vytorin in July 2004.

PRESCRIPTION: Yes

GENERIC AVAILABLE: No

PREPARATIONS: Tablets of 10/10, 10/20, 10/40, and 10/80 mg (ezetimibe/simvastatin)

STORAGE: Vytorin should be stored at room temperature, 20°-25°C (68°-77°F).

PRESCRIBED FOR: Vytorin is used for reducing total cholesterol, LDL cholesterol and triglycerides, and increasing HDL cholesterol.

DOSING: The recommended dose range of Vytorin is 10/10 mg to 10/80 mg, and it is administered once daily in the evening with or with out food. Therapy is usually initiated with 10/20 mg daily, but individuals who need more than a 55% reduction in LDL cholesterol can be started on 10/40 mg daily.

DRUG INTERACTIONS: Vytorin contains simvastatin (Zocor), and numerous drugs block the elimination of simvastatin by the liver. Decreased elimination of simvastatin could increase the levels of simvastatin in the body and increase the risk of muscle toxicity from simvastatin. Vytorin should not be combined with drugs that decrease its elimination. Examples of these drugs include erythromycin (E-Mycin), ketoconazole (Nizoral), itraconazole (Sporanox), clarithromycin (Biaxin), telithromycin (Ketek), cyclosporine (Sandimmune), nefazodone (Serzone), and HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir). Large quantities of grape fruit juice (>1 quart daily) also will increase blood levels of simvastatin.

Amiodarone (Cordarone), verapamil (Calan Verelan, Isoptin), danazol (Danocrine), cyclosporine (Gengraf, Neoral), niacin (Niacor, Niaspan, Slo-Niacin), gemfibrozil (Lopid) and fenofibrate (Tricor) also may increase the risk of muscle toxicity when combined with simvastatin. Patients taking amiodarone or verapamil should not exceed 10/20 mg of Vytorin. Patients taking danazol or cyclosporine should not exceed 10/10 mg of Vytorin.

Simvastatin increases the effect of warfarin (Coumadin) and the blood concentration of digoxin (Lanoxin). Patients taking simvastatin and warfarin or digoxin should be monitored carefully.

Cholestyramine (Questran) decreases the absorption of ezetimibe (Zetia). Administer Vytorin 2 hours before or at least 4 hours after cholestyramine administration.

PREGNANCY: Vytorin should not be taken during pregnancy because the developing fetus requires cholesterol for development and Vytorin, due to the simvastatin component, reduces the production of cholesterol. Vytorin should only be administered to women of child bearing age if they are not likely to become pregnant.

NURSING MOTHERS: Because of the risk of adverse effects to the developing infant, Vytorin should not be administered to nursing mothers.

SIDE EFFECTS: The most common side effects of Vytorin are headache, nausea, vomiting, diarrhea, muscle pain, and abnormal liver tests. Hypersensitivity reactions have also been reported. The most serious potential side effects are liver damage and muscle inflammation or breakdown.

The simvastatin component of Vytorin is a statin. Therefore it shares side effects, such as liver and muscle damage associated with statins. Serious liver damage caused by statins is rare. More often, statins cause abnormalities of liver tests, and, therefore, periodic measurement of liver tests in the blood is recommended for all statins. Abnormal tests usually return to normal even if a statin is continued, but if the abnormal test value is greater than three times the upper limit of normal, the statin usually is stopped. Liver tests should be measured before Vytorin is started and periodically thereafter or if there is a medical concern about liver damage. Liver tests should be performed before the 10/80 mg dose of Vytorin is initiated, three months after initiation and then periodically thereafter.

Inflammation of the muscles caused by statins can lead to a serious breakdown of muscle cells called rhabdomyolysis. Rhabdomyolysis causes the release of muscle protein (myoglobin) into the blood. Myoglobin can cause kidney failure and even death. When used alone, statins cause rhabdomyolysis in less than one percent of patients. To prevent the development of rhabdomyolysis, patients taking Vytorin should contact their healthcare provider immediately if they develop unexplained muscle pain, weakness, or muscle tenderness.

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