title: Striated muscle safety of ezetimibe/simvastatin (Vytorin).
abstract: Despite the excellent benefit/risk profile of statins, their use is limited by a dose-related risk of adverse events, particularly those related to muscle toxicity. Ezetimibe/simvastatin (Vytorin) is a cholesterol-lowering therapy that inhibits the intestinal absorption (ezetimibe) and synthesis (simvastatin) of cholesterol. This analysis compared the muscle safety profiles of ezetimibe/simvastatin and simvastatin monotherapy. We reviewed muscle-related adverse event (AE) data from 17 randomized, blinded clinical trials (13 base and 4 extension studies), in which ezetimibe and simvastatin were either co-administered as separate entities or given as a combination tablet to 4,558 patients. The following AE categories were summarized: incidence of musculoskeletal or connective-tissue AEs (all and drug related); discontinuations due to musculoskeletal or connective-tissue AEs (all and drug related); incidence of AEs reported under the term "myalgia" (all and drug related); discontinuation due to myalgia (all and drug related); incidence of "myopathy" (all and drug related); increases in creatine kinase to 3 to < 5, 5 to < 10, and > or = 10 times the upper limit of normal. For all AE categories examined, the incidence of muscle-related clinical and laboratory AEs or discontinuations due to muscle-related AEs was no more common in patients taking ezetimibe/simvastatin than in those taking simvastatin alone. Thus, the clinical trial experience with ezetimibe/simvastatin suggests that ezetimibe does not enhance or aggravate the muscle effects of simvastatin.
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA. michaeldavidson@radiantresearch.com
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davidson
authors.forename: Darbie
authors.initials: D
authors.lastname: Maccubbin
authors.forename: Michael
authors.initials: M
authors.lastname: Stepanavage
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.forename: Thomas
authors.initials: T
authors.lastname: Musliner
mesh_terms: D001384:Azetidines / Q000009:adverse effects / Q000494:pharmacology*; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin