Simvastatin: a review of its pharmacology and clinical use

Simvastatin, a chemical derivative of lovastatin, is an antihyperlipidemic medication that inhibits hydroxymethylglutaryl coenzyme A reductase. Animal and clinical data suggest simvastatin is twice as potent as lovastatin. It lowers serum cholesterol by inhibiting hepatic synthesis of cholesterol and, more importantly, by increasing the number of low-density lipoprotein (LDL) receptors present on hepatic cellular membranes. Simvastatin, when used at doses of 40 mg/d in patients with heterozygous familial hypercholesterolemia, significantly reduces total cholesterol (greater than 30 percent) and LDL cholesterol (35-45 percent) and tends to reduce triglycerides and raise high-density lipoprotein (HDL) cholesterol. The agent is also effective in patients with polygenic hypercholesterolemia, familial dysbetalipoproteinemia, and nephrotic syndrome. Addition of cholestyramine to simvastatin enhances the LDL cholesterol-lowering effect to approximately 55 percent. Common clinical adverse effects reported with simvastatin use include headaches and gastrointestinal complaints. Transient elevations in serum transaminases and creatine phosphokinase have also been seen. Based on data currently available, the drug's clinical activity and adverse-effect profile are similar to those of lovastatin. Therefore, there is no need for formularies to contain both medications. To choose between the two, one needs to consider the incidence of adverse effects and the daily cost of each product when used at equally effective doses. That information is now now available and, until it is, a clear recommendation cannot be made. Simvastatin, presently marketed in several countries, is investigational in the U.S. but is expected to be available soon.