Fenofibrate in the Management of Lipid Abnormalities
Fenofibrate in the Management of Lipid Abnormalities
Human immunodeficiency virus (HIV) protease inhibitors are associated with several metabolic abnormalities including hypercholesterolemia and hypertriglyceridemia. Fenofibrate is a new lipid-lowering agent for adults with very high triglyceride levels that was administered to two HIV-positive patients who were taking protease inhibitors and developed hypertriglyceridemia. Starting dosages were 134 and 201 mg/day, and were increased to 268 mg/day in both patients. Triglyceride levels decreased from 1450 to 337 mg/dl (76.8%) and from 1985 to 322 mg/dl (83.8%), respectively, after 10 months of therapy. High-density lipoprotein levels increased in both patients.
The combination of human immunodeficiency virus (HIV) protease inhibitors and reverse transcriptase inhibitors is recommended as standard antiretroviral therapy. Protease inhibitors confer virologic, immunologic, clinical, and survival benefits. Therapy is begun early and aggressively, with most patients treated with combinations of three or four drugs, including a protease inhibitor. However, all protease inhibitors may be associated with development of metabolic abnormalities, including hypercholesterolemia, hyper-triglyceridemia, insulin resistance, glucose intolerance or diabetes mellitus, and lipodystrophies.
In non-HIV-infected persons, hyper-triglyceridemia greater than 1000 mg/dl is associated with an increased risk of pancreatitis. Patients with HIV infection may be at higher risk for pancreatitis because of drug toxicities, immunodeficiency, and protease inhibitor-associated hypertriglyceridemia. In addition, hypertriglyceridemia and hypercholesterolemia are associated with increased risk of coronary artery disease (CAD). In patients with HIV infection, this increased risk may be due to a high rate of concomitant chlamydial and cytomegalovirus infections, both of which are associated with CAD and acute myocardial infarction. Isolated cases of pancreatitis and cardiovascular disease in patients with lipid changes secondary to protease inhibitors also have been reported.
The number of lipid-lowering prescriptions is increasing for persons taking protease inhibitors with elevations in cholesterol and triglycerides. National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) guidelines do not specifically address protease inhibitor-induced lipid changes, although cholesterol-lowering agents have been administered in this setting.
Due to potential complications of hyper-lipidemia, HIV-infected patients taking protease inhibitors could benefit from additional treatment options. Micronized fenofibrate (Tricor) is a fibric acid derivative approved by the Food and Drug Administration for the treatment of Fredrickson types IV and V hyperlipidemia. The literature also supports the drug in Fredrickson types IIa, IIb, and III hyperlipidemia.
Human immunodeficiency virus (HIV) protease inhibitors are associated with several metabolic abnormalities including hypercholesterolemia and hypertriglyceridemia. Fenofibrate is a new lipid-lowering agent for adults with very high triglyceride levels that was administered to two HIV-positive patients who were taking protease inhibitors and developed hypertriglyceridemia. Starting dosages were 134 and 201 mg/day, and were increased to 268 mg/day in both patients. Triglyceride levels decreased from 1450 to 337 mg/dl (76.8%) and from 1985 to 322 mg/dl (83.8%), respectively, after 10 months of therapy. High-density lipoprotein levels increased in both patients.
The combination of human immunodeficiency virus (HIV) protease inhibitors and reverse transcriptase inhibitors is recommended as standard antiretroviral therapy. Protease inhibitors confer virologic, immunologic, clinical, and survival benefits. Therapy is begun early and aggressively, with most patients treated with combinations of three or four drugs, including a protease inhibitor. However, all protease inhibitors may be associated with development of metabolic abnormalities, including hypercholesterolemia, hyper-triglyceridemia, insulin resistance, glucose intolerance or diabetes mellitus, and lipodystrophies.
In non-HIV-infected persons, hyper-triglyceridemia greater than 1000 mg/dl is associated with an increased risk of pancreatitis. Patients with HIV infection may be at higher risk for pancreatitis because of drug toxicities, immunodeficiency, and protease inhibitor-associated hypertriglyceridemia. In addition, hypertriglyceridemia and hypercholesterolemia are associated with increased risk of coronary artery disease (CAD). In patients with HIV infection, this increased risk may be due to a high rate of concomitant chlamydial and cytomegalovirus infections, both of which are associated with CAD and acute myocardial infarction. Isolated cases of pancreatitis and cardiovascular disease in patients with lipid changes secondary to protease inhibitors also have been reported.
The number of lipid-lowering prescriptions is increasing for persons taking protease inhibitors with elevations in cholesterol and triglycerides. National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) guidelines do not specifically address protease inhibitor-induced lipid changes, although cholesterol-lowering agents have been administered in this setting.
Due to potential complications of hyper-lipidemia, HIV-infected patients taking protease inhibitors could benefit from additional treatment options. Micronized fenofibrate (Tricor) is a fibric acid derivative approved by the Food and Drug Administration for the treatment of Fredrickson types IV and V hyperlipidemia. The literature also supports the drug in Fredrickson types IIa, IIb, and III hyperlipidemia.
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