title: Relative safety of gemfibrozil and fenofibrate in the absence of concomitant cerivastatin use.
abstract: Previous analyses of fibrate safety may have been driven by a higher propensity for gemfibrozil to interact with cerivastatin, which is currently off the market because of safety concerns. We reviewed gemfibrozil- and fenofibrate-associated adverse event reports (AERs) submitted to the US Food and Drug Administration over a 5-year period. To control for cerivastatin's impact on fibrate-associated AERs, reports with concomitant cerivastatin use were excluded. Rates per million prescriptions were calculated for all AERs, serious AERs, rhabdomyolysis AERs, muscle-related AERs without rhabdomyolysis, and liver AERs. The rates of all AERs (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.69 to 0.83), serious AERs (OR 0.72, 95% CI 0.65 to 0.81), and liver AERs (OR 0.37, 95% CI 0.28 to 0.50) were significantly lower for gemfibrozil compared with fenofibrate (p <0.001 for each). In contrast, rates of rhabdomyolysis AERs (OR 2.67, 95% CI 2.11 to 3.39, p <0.001) and muscle-related AERs without rhabdomyolysis (OR 1.36, 95% CI 1.12 to 1.71, p = 0.002) were significantly higher for gemfibrozil compared with fenofibrate. In conclusion, the safety profiles of fibrates differ, with a higher rate of liver-related AERs associated with fenofibrate and a higher rate of muscle-related AERs associated with gemfibrozil. Rates of all AERs and serious AERs were higher with fenofibrate, but well within the range observed with commonly used lipid-altering medications.
authors.affiliation: Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Noa
authors.initials: N
authors.lastname: Holoshitz
authors.forename: Alawi A
authors.initials: AA
authors.lastname: Alsheikh-Ali
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D056486:Chemical and Drug Induced Liver Injury; D016208:Databases, Factual; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D011345:Fenofibrate / Q000009:adverse effects*; D015248:Gemfibrozil / Q000009:adverse effects*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008107:Liver Diseases / Q000453:epidemiology; D009135:Muscular Diseases / Q000139:chemically induced / Q000453:epidemiology; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D000960:Hypolipidemic Agents; D015248:Gemfibrozil; D011345:Fenofibrate