Safety considerations with fenofibrate/simvastatin combination

Abstract

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.

Chronic kidney disease stage affects small, dense low-density lipoprotein but not glycated low-density lipoprotein in younger chronic kidney disease patients: a cross-sectional study

“…Possible options are fibrates and LDL apheresis, however, fibrates are often not well tolerated and LDL apheresis is invasive and access to this treatment modality is limited [ 35 ]. Newer fibrates such as fenofibrate in a simvastatin combination have recently demonstrated good safety profiles in adults and even reduced proteinuria [ 36 ].…”

Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy

“… 49 – 52 The underlying mechanism could be an increase of adiponectin (insulin sensitizer) in adipose tissue. 53 …”

The importance of cardiovascular disease in pediatric transplantation and its link to the kidneys

“…Statins were designed for familial hypercholesterolemia due to LDL receptor defects and do not affect the small dense LDL fractions . Newer fibrates such as fenofibrate in a simvastatin combination have recently demonstrated good safety profiles in adults and even reduced proteinuria . It should also be noted that immunosuppression, especially mTOR inhibitors and cyclosporine, contributes to the dyslipidemia …”

“…However, as discussed above, statins were designed for familial hypercholesterolemia patients and do not affect small dense LDL. Fenofibrate in a simvastatin combination may be a better option, but its safety and efficacy in children needs to be established. A referral to cardiology or endocrinology that treat dyslipidemias (depending on the specific services for each center) should be implemented promptly.…”