Safety considerations with fenofibrate/simvastatin combination

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• adverse effects
• cardiovascular disease
• drug interactions
• fenofibrate
• mixed dyslipidemia
• pharmacokinetics
• safety
• simvastatin
• tolerability

Declaration of interest

This review was conducted independently; no company or institution supported it financially. MS Elisaf has received speaker honoraria, consulting fees, and research funding from AstraZeneca, Schering Plough, Merck, Pfizer, Solvay, Abbott, Boehringer Ingelheim, and Fournier, and has participated in clinical trials with AstraZeneca, Merck, Sanofi-Synthelabo, Solvay, Glaxo, Novartis, Pfizer, and Fournier. The authors have given talks and attended conferences sponsored by various pharmaceutical companies, including Bristol-Myers Squibb, Pfizer, Lilly, Abbott, Amgen, Astrazeneca, Novartis, Vianex, Teva, and MSD.