title: Safety considerations with fenofibrate/simvastatin combination.
abstract: BACKGROUND
  Fenofibrate/simvastatin combination is useful for patients with mixed dyslipidemia. Aim of this review is to critically present the safety aspects of the fenofibrate/simvastatin combination.
  
  
  METHODS
  Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies. Additionally, clinical pharmacology, drug interactions and the effects of fenofibrate and simvastatin on metabolic variables and cardiovascular risk are briefly described.
  
  
  CONCLUSIONS
  Large randomized clinical trials show that the combined administration of fenofibrate with simvastatin is not associated with significantly increased incidence of serious adverse events compared with simvastatin monotherapy. The incidence of rhabdomyolysis is slightly increased with fibrate/statin combination compared with monotherapy but the actual risk is very low. Although fenofibrate increases creatinine and homocysteine serum levels, the incidence of diabetic nephropathy and thrombotic events was not significantly increased with fenofibrate/simvastatin combination compared with simvastatin monotherapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. Furthermore, a decrease in albuminuria was observed with fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and ACCORD Lipid trials. Overall, the combined administration of fenofibrate with simvastatin appears to be safe, unless clinicians give fenofibrate/simvastatin combination to patients with predisposing risk factors for the occurrence of adverse events.
authors.affiliation: a 1 University of Ioannina, School of Medicine, Department of Internal Medicine , 45 110 Ioannina, Greece.
authors.forename: Theodosios D
authors.initials: TD
authors.lastname: Filippatos
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D004338:Drug Combinations; D004347:Drug Interactions; D050171:Dyslipidemias / Q000188:drug therapy*; D011345:Fenofibrate / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D019821:Simvastatin; D011345:Fenofibrate
keywords: adverse effects; cardiovascular disease; drug interactions; fenofibrate; mixed dyslipidemia; pharmacokinetics; safety; simvastatin; tolerability