Nicostatin, rosuvastatin, ezetimibe to debut soon. (Excellent Safety Profiles).
Nicostatin (Advicor) received Food and Drug Administration approval in December and is now reaching pharmacy shelves. But physicians may not get deluged with drug detail people promoting the product, since its manufacturer, Kos Pharmaceuticals Inc., is a relatively small company that has decided not to take on a marketing partner, said Dr. Hunninghake, professor of pharmacology and medicine at the University of Minnesota, Minneapolis.
Rosuvastatin and ezetimibe are expected to win FDA approval without difficulty later this year. All three drugs have excellent safety profiles. Each offers notable advantages over existing therapies in terms of efficacy and/or convenience, he added.
Nicostatin combines extended-release niacin with lovastatin, which on Dec. 16, 2001, became the first generic statin. The combined effects of the two drugs on LDL and HDL cholesterol and triglycerides are greater than that of either agent alone, making nicostatin particularly useful in patients with combined hyperlipidemia. The profile of many patients with coronary heart disease is one of modestly elevated LDL, low HDL, and elevated triglycerides, a setting where nicostatin shines.
The drug is given once daily at bedtime. It comes in three dosages: niacin 500 mg/lovastatin 20 mg, niacin 750 mg/lovastatin 20 mg, and niacin 1,000 mg/lovastatin 20 mg.
The maximum recommended dosage is niacin 2,000 mg/lovastatin 40 mg. Studies indicate that this typically achieves a 44% reduction in LDL, a 43% reduction in triglycerides, and a 30% gain in HDL. It also results in a 22% reduction in lipoprotein (a), although there aren't yet good data showing that this lowers risk.
The chief side effect is flushing due to the niacin component. It has led to discontinuation in 7%-10% of patients in clinical trials; the rate in practice will probably be a little higher.
Nicostatin results in a modest increase in plasma glucose, but data in type 2 diabetic patients suggest that there's no need for major adjustments in antidiabetic medications. An area where more data are needed involves the drug's use in patients with the metabolic syndrome. It's unknown whether the increased plasma glucose will tip some patients into type 2 diabetes, he cautioned.
Rosuvastatin (Crestor), an AstraZeneca drug, is the most potent LDL-lowering drug to date. In small studies, rosuvastatin has resulted in roughly an absolute 8% greater reduction in LDL than the same dosage of atorvastatin. At 80 mg/day projected to be the maximum recommended dosage of rosuvastatin, patients typically achieve a 58% reduction in LDL, compared with 50% with atorvastatin.
Rosuvastatin appears to have a greater HDL-raising effect than other statins. At 20 mg/day for example, rosuvastatin boosts HDL by 12%, compared with 5% for atorvastatin. With fasting triglycerides of 300-800 mg/dL, 10 mg/day of rosuvastatin resulted in a 37% reduction in triglycerides.
Ezetimibe, a Schering-Plough drug, has a unique mechanism of action. It inhibits cholesterol absorption both from the gut and the enterohepatic circulation. The once-daily 10-mg tablet expected to be approved typically lowers LDL by 18%. Ezetimibe also decreases atherogenic remnant particles, meaning that the drug theoretically results in a greater reduction in cardiovascular risk than is suggested by its modest effect upon LDL.
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|Publication:||Internal Medicine News|
|Date:||Feb 15, 2002|
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