Micronized fenofibrate: A new fibric acid hypolipidemic agent

OBJECTIVE: To review the efficacy and safety of fenofibrate in the manageme nt of hyperlipidemias. DATA SOURCES: A MEDLINE search (1974-October 1998), Current Contents search , additional references from article bibliographies, and the package insert from the manufacturer were used to identify data for evaluation. Studies e valuating fenofibrate (peer-reviewed publications, package insert data) wer e considered for inclusion. Abstracts and data on file with the manufacture r were not considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the p harmacology, pharmacokinetics, clinical use, and tolerability of fenofibrat e. Data from animals and in vitro systems were included only when necessary to explain the drug's pharmacology. DATA SYNTHESIS: Micronized fenofibrate is a fibric acid derivative approved by the Food and Drug Administration (FDA) in February 1998 for the treatme nt of types IV and V hyperlipidemia. Data from the peer-reviewed literature also support the use of fenofibrate in types IIa, IIb, and III hyperlipide mias. Micronized fenofibrate 67-201 mg/d is useful as monotherapy or as an adjunct to other hypolipidemics and dietary therapy. In placebo-controlled clinical trials, regular formulation fenofibrate 300-400 mg/d lowered serum triglyceride (TG) concentrations by 24-55%, total cholesterol by 9-25%, lo w-density lipoprotein cholesterol (LDL-C) concentrations by 6-35%, and rais ed high-density lipoprotein cholesterol (HDL-C) concentrations by 8-38%. Fe w comparative data exist regarding fenofibrate versus clofibrate and gemfib rozil. In noncomparative and comparative clinical trials, fenofibrate appea red to be well tolerated. The most common causally related adverse events w ere digestive, musculoskeletal, and dermatologic in nature. Concurrent use of fenofibrate and a hydroxymethylglutaryl-coenzyme A inhibitor may increas e the risk of myopathy and/or rhabdomyolysis, although recent data suggest that concurrent use of fenofibrate with low-dose simvastatin or pravastatin is safe. Fenofibrate may enhance the effect of oral anticoagulants. CONCLU SIONS: Fenofibrate reduces serum TG, total cholesterol, and LDL-C, and rais es HDL-C to clinically relevant degrees. Its spectrum of activity appears t o exceed that recommended for types IV and V hyperlipidemia to encompass ty pes IIa, IIb, and III hyperlipidemias as well. To this extent, it may be co nsidered a broader-spectrum fibrate than is indicated by its FDA approval. Adverse effects of fenofibrate appear to be similar to those of other fibra tes and require routine monitoring (clinical, liver function). Long-term sa fety data are readily available from drug registries in many countries wher e the product has been available for nearly two decades. Cost-effectiveness studies comparing fenofibrate with other hypolipidemics demonstrate benefi ts of fenofibrate over simvastatin in types IIa and IIb hyperlipidemia. The need for dosage titration of the micronized preparation from 67 mg/d upwar d to a final dose of 200 mg/d is also not supported by peer-reviewed litera ture (except in the case of renal impairment). Although preliminary data on plaque regression are encouraging, published clinical studies evaluating t he impact of fenofibrate on cardiovascular morbidity and mortality are awai ted. Micronized fenofibrate is worthy of formulary inclusion.