Potential use of fenofibrate and other fibric acid derivatives in the clinic

Abstract

The fibric acid derivatives continue to have a place in the treatment of hyperlipidemia. The third generation of these drugs, including fenofibrate, appears to offer some advantages over those currently available in the United States. These drugs should be prescribed only after dietary and lifestyle changes have been offered as the preferable treatment. In severe hypertriglyceridemia, clofibrate, gemfibrozil, or fenofibrate may reduce the very low-density lipoprotein and chylomicron levels adequately. Dysbetalipoproteinemia may also be completely controlled by a combination of diet and any one of these drugs. When the low-density lipoprotein level is elevated, the newer fibric acid derivatives, such as fenofibrate, may be more effective in lowering the plasma cholesterol levels. This is true for those patients with elevated low-density lipoprotein and normal very low-density lipoprotein triglyceride levels, as well as those with elevated very low-density lipoprotein triglyceride levels. A 20 percent reduction in low-density lipoprotein cholesterol levels is expected when the triglyceride levels are not elevated. When the very low-density lipoprotein triglyceride levels are elevated, the low-density lipoprotein response is more variable, and on occasion the low-density lipoprotein cholesterol level may rise as the very low-density lipoprotein level is reduced. The average reduction in low-density lipoprotein cholesterol levels (about 6 percent) caused by fenofibrate may be greater in patients with elevated very low-density lipoprotein triglyceride levels than by other fibrates. In combination with other agents that lower low-density lipoprotein levels more specifically, such as the bile acid sequestrants and hydroxymethylglutaryl coenzyme A reductase inhibitors, fenofibrate may act to effect control of the triglycerides allowing management of those patients with disorders producing elevated very low-density lipoprotein triglyceride levels than by other fibrates. Extensive European experience with fenofibrate (six million patient-years) indicates that severe side effects are unlikely. However, the physician should monitor patients for skin rash, liver and renal function abnormalities, gastrointestinal dysfunction, and generalized muscle tenderness. All of these usually appear very early in the course of treatment and are reversible. Of greater concern is the possibility of an increased incidence of cholethiasis, since the bile becomes relatively enriched in cholesterol during therapy with any fibric acid derivative. The chance of experiencing this side effect may depend on the patient's propensity to the development of cholelithiasis, since the actual incidence of this problem during fenofibrate therapy appears to be quite small and has not been well defined.