Vytorin has been approved as adjunctive therapy to diet for reduction of elevated total cholesterol.
Although an estimated 37 million Americans could benefit from lipid-lowering drugs, only about 14 million people in this country take them. This statistic could soon change, however. National Cholesterol Education Program guidelines now recommend that those who have had a myocardial infarction (MI) or are at high risk for cardiovascular disease lower their low-density lipoprotein (LDL) cholesterol to 70 mg/dL.
The Food & Drug Administration recently approved ezetimibe/simvastatin (Vytorin, Merck/Schering-Plough Pharmaceuticals) as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and non-high-density lipoprotein (HDL) cholesterol and to increase HDL cholesterol in those with primary hypercholesterolemia or mixed hyperlipidemia. The drug is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in those with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering therapies or if such treatments are unavailable.
According to Merck/Schering-Plough, ezetimibe/simvastatin is the first and only product approved to reduce LDL cholesterol through dual inhibition of the two sources of cholesterol with one tablet. The drug will be widely available in U.S. pharmacies in the near future.
The availability of simvastatin (Zocor) and ezetimibe (Zetia) in one drug should improve patient compliance, remarked Judy Cheng, Pharm.D., an associate professor of pharmacy practice at the Arnold & Marie Schwartz College of Pharmacy and Health Sciences at Long Island University in Brooklyn, N.Y. In addition, paying one price for a combination product makes more financial sense than paying for two separate drugs, she said.
Cheng said that the key issue relevant to this product concerns the best way to help patients reach the new, more stringent cholesterol goals. If the statin dose is increased, she said, so, too, is the risk of myopathy/rhabdomyolysis and hepatic toxicity.
Very strong data suggest, however, that aggressive, high-dose statin therapy reduces MI risk in addition to lowering LDL cholesterol levels, Cheng noted. On the other hand, although ezetimibe is not associated with increased adverse effects when added to statin therapy, no clinical data to date indicate that the drug reduces the risk of MI.
No new or additive adverse effects are associated with this combination product, Cheng said. The manufacturer cautioned that the concomitant use of ezetimibe/simvastatin with inhibitors of the cytochrome P450 3A4 enzyme system is contraindicated. The concomitant use of the drug with fibrates is also contraindicated.
Across the dosing range, the ezetimibe component of Vytorin is held constant at 10 mg; the simvastatin component ranges from 10 mg to 80 mg. The recommended starting dose is 10/20 mg, taken once daily. The recommended dosage for those with homozygous familial hypercholesterolemia is 10/40 mg or 10/80 mg, taken once daily in the evening.
Dosage adjustment is unnecessary in older persons. It is also unnecessary in those with mild hepatic insufficiency. Ezetimibe/simvastatin is not recommended for use in those with moderate to severe hepatic insufficiency. It is contraindicated in those with active liver disease or unexplained persistent elevations in serum transaminases.
Dosage adjustment is unnecessary as well in those with mild to moderate renal insufficiency, according to the company. Therapy with this product should not be started in those with severe renal insufficiency unless the patient has tolerated simvastatin therapy at a dose of 5 mg or higher.
Ezetimibe/simvastatin treatment should not be initiated in those taking cyclosporine unless they have already tolerated therapy with simvastatin at a dose of 5 mg or higher. The dose of ezetimibe/simvastatin should not exceed 10/10 mg daily in these patients. The dose should not exceed 10/20 mg daily in those taking amiodarone or verapamil.
For those who still need to lower their LDL cholesterol level after therapy with a maximally tolerated statin dose, ezetimibe/simvastatin is an excellent therapeutic option, Cheng concluded.
Charlotte LoBuono. New combo makes it more convenient to lower cholesterol. Drug Topics Aug. 23, 2004;148:24.