Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients.
Treatment with fenofibrate results in increases in high-density lipoprotein (HDL) and apoproteins apo AI and apo AII.
Decreases serum uric acid levels by 20-30%.
The use of extended release niacin and fenofibrate have not provided mortality benefit when added to statin therapy, despite widespread use.
Meta-analyses showed no improvement in survival with the use of fenofibrates and this was confirmed in the ACCORD trial (Studer M et al).
Marketed as Tricor is a drug of the fibrate class.
It is mainly used to reduce cholesterol levels in people at risk of cardiovascular disease.
It reduces both low-density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, as well as increasing high-density lipoprotein (HDL) levels and reducing triglyceride levels.
Enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
Can be used alone or along with statins in the treatment of hypercholesterolemia and hypertriglyceridemia.
Due to lack of cardiovascular benefit and the risk of side effects such as muscle damage, the FDA withdrew approval for the use in high cholesterol treatment in combination with statins.
It is mainly used for primary hypercholesterolemia or mixed dyslipidemia.
Fenofibrate appears to decrease the risk of cardiovascular disease and possibly diabetic retinopathy in those with diabetes mellitus, and appears to be helpful in decreasing amputations in this same group.
Has an off-label use for hyperuricemia in people who have gout.
Used, in addition to diet to reduce elevated low-density lipoprotein cholesterol (LDL), total cholesterol, triglycerides (TG), and apolipoprotein B (apo B), and to increase high-density lipoprotein cholesterol (HDL) in adults with primary hypercholesterolemia or mixed dyslipidemia.
Used in addition to diet for treatment of adults with severe hypertriglyceridemia.
In 2016, the FDA concluded that the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events.
FDA has determined that the benefits of niacin and fenofibric capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn.
Fenofibrate is contraindicated in:
Patients with severe renal impairment,
Patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function test abnormalities
Patients with preexisting gallbladder disease.
Nursing mothers.
Adverse effects The most common adverse events with coadministered statins are:
Headache
Back pain
Nasopharyngitis
Nausea
Myalgia
Joint pain or arthralgia
Diarrhea
Upper respiratory tract infection
Myopathy and rhabdomyolysis; increased risk when coadminstered with a statin, particularly in the elderly and patients with diabetes, renal failure, hypothyroidism.
Can increase serum transaminases, so that liver tests should be monitored periodically
Can increase serum creatinine levels and renal function should be monitored periodically in patients with renal insufficiency.
Can increase cholesterol excretion into the bile, leading to risk of cholelithiasis.
Exercise caution in concomitant treatment with oral anticoagulants
Bile acid sequestrants may bind to fenofibrate, resulting in a decrease in fenofibrate absorption.
To maximize absorption, patients need to separate administration by at least 1 h before or 4 h to 6 h after taking the bile acid sequestrant.
An increased risk of renal dysfunction exists with concomitant use of immunosuppressants and fenofibrate.
Caution required when coadministering additional medications that decrease renal function.
Combination of statins and fenofibrate may increase the risk of rhabdomyolysis or myopathy.
Fenofibrate is a fibric acid derivative, a prodrug comprising fenofibric acid linked to an isopropyl ester.
Fenofibrate lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα).
PPARα activates lipoprotein lipase and reduces apoprotein CIII, which increases lipolysis and elimination of triglyceride-rich particles from plasma.
The active form of fenofibrate, fenofibric acid, is also available and may be taken without regard to the timing of meals.
When fenofibrate and a statin are given as combination therapy, it is recommended that fenofibrate be given in the morning and the statin at night, so that the peak dosages do not overlap.