FDA approves ezetimibe/ simvastatin combination

Drug must be weighed against single agents

Health care providers now have another choice of cholesterol-lowering treatments. The FDA recently approved the combination of two cholesterol drugs, ezetimibe (Zetia) and simvastatin (Zocor), into a single pill. The product is being marketed under the name Vytorin. It is administered as a once-daily tablet and should be taken in the evening with or without food.

The marketers of the drug, Merck & Co. and Schering-Plough Pharmaceuticals, say the ezetimibe/simvastatin drug is the first single cholesterol treatment to provide LDL cholesterol lowering through dual inhibition of cholesterol production and absorption. Ezetimibe limits the absorption of cholesterol in the intestines; simvastatin interferes with the production of cholesterol in the liver. The FDA approved the combination drug for the treatment of high LDL cholesterol in patients with primary hypercholesterolemia or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. 

Some industry analysts feel physicians might opt for this new combination drug, especially in light of concerns about side effects such as severe muscle deterioration and kidney damage from the use of rosuvastatin calcium (Crestor).

Physicians, however, will naturally turn to those drugs or products that will give the most lowering, says James M. McKenney, PharmD, emeritus professor at the School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University and president and CEO of National Clinical Research both in Richmond.

"That’s where you begin to look at drugs like Lipitor (atorvastatin) and Crestor. Vytorin does provide comparable or nearly comparable LDL reductions to those two potent statins. It gives you a choice," he says. "We can argue the point of whether it is better to give the patient two drugs in a combination product or just give them one statin, even in a low dose like Crestor, that can accomplish the lowering that you need by itself."

More details about Vytorin

In a 12-week, multicenter, double-blind, placebo-controlled clinical study of 1,528 patients with LDL cholesterol levels of 145-250 mg/dL, the ezetimibe/simvastatin drug provided LDL cholesterol reductions of 52% at the recommended starting dose (10/20 mg), 55% at the 10/40 mg dose, and 60% at the maximum dose (10/80 mg). The manufacturers also claim that in head-to-head trials, the combination drug provided greater reductions in LDL cholesterol than atorvastatin and simvastatin across the dosing range.

Ezetimibe/simvastatin also was evaluated for safety in more than 3,800 patients in clinical trials and was generally well tolerated at all doses. In clinical trials, the most commonly reported side effects, regardless of cause, included headache (6.8%), upper respiratory tract infection (3.9%), myalgia (3.5%), influenza (2.6%), and extremity pain (2.3%).

The ezetimibe/simvastatin combination has been approved for use in patients at the following doses: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg. Across the dosing range, the ezetimibe component is held constant at 10 mg, while the simvastatin component ranges from 10 mg to 80 mg. The recommended starting dose for the drug is 10/20 mg. Patients requiring LDL cholesterol reductions greater than 55% can be started on 10/40 mg. Patients requiring less aggressive LDL cholesterol reductions may be started at 10/10 mg. The dose of ezetimibe/simvastatin should be limited to 10/10 mg daily in patients on cyclosporine and 10/20 mg daily in patients on amiodarone or verapamil.

Each dose is expected to cost the same: $2.34, according to statements published by the manufacturers. The drug should be broadly available in pharmacies soon.