General Information

Tricor (fenofibrate) is a peroxisome proliferator-activated receptor (PPAR) alpha agonist

Tricor tablets are indicated as an adjunct to diet:

To reduce elevated LDL-C, Total-C, TG and Apo B, and to increase HDLC in adult patients with primary hypercholesterolemia or mixed dyslipidemia

For treatment of adult patients with severe hypertriglyceridemia

Tricor tablets may be taken without regard to meals. The recommended dosing is as follows:

Primary hypercholesterolemia or mixed dyslipidemia: Initial dose of 145 mg once daily

Severe hypertriglyceridemia: Initial dose of 48 to 145 mg once daily. Maximum dose is 145 mg

Renally impaired patients: Initial dose of 48 mg once daily

Geriatric patients: Select the dose on the basis of renal function

Mechanism of Action

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. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apoproteins apoAI and apoAII.

The effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor alpha (PPAR alpha). Through this mechanism, fenofibrate increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity). The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly. Activation of PPAR alpha also induces an increase in the synthesis of apoproteins A-I, A-II and HDL-cholesterol.

Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.

Clinical Trial Results

TriCor (160 mg per day) was evaluated in four randomized, placebo-controlled, double-blind, parallel-group trials as a therapy for hypercholesterolemia and mixed dyslipidemia. Treatment with TriCor was shown to lower LDL-C, Total-C, the LDL-C/HDL-C ratio and triglycerides, in addition to raising HDL-C. Apo-B levels were also measured in a subset of subjects. Compared to placebo, treatment with TriCor significantly reduced Apo-B from baseline to endpoint.

The effect of TriCor on serum triglycerides was evaluated in two randomized, double-blind, placebo-controlled trials that included 147 hypertriglyceridemic subjects. Treatment was administered for eight weeks in both trials. The trials differed in terms of initial subject triglyceride (TG) levels; one entered subjects with baseline TG levels of 500 to 1500 mg/dL, and the other entered subjects with TG levels of 350 to 500 mg/dL. In subjects with hypertriglyceridemia and normal cholesterolemia with or without hyperchylomicronemia, treatment with TriCor decreased very low density lipoprotein (VLDL) triglycerides and VLDL cholesterol.