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The fibrates, or fibric acid derivatives, act in part to stimulate the activity of peroxisome proliferator-activated receptors (PPARs), which are involved in fatty acid breakdown. The main action of fibrates is to lower triglyceride levels (by 35 to 50 percent). Fibrates also raise serum high density lipoprotein (HDL) by 15 to 25 percent. Fibrates are the drugs of choice when treating isolated elevated triglycerides. They can be combined with statins to treat combinations of high triglycerides and LDL cholesterol.

Clofibrate (atromid-s ®)

INDICATIONS: Adjunct to dietary therapy in the management of hyperlipidemias associated with high triglyceride levels (types III, IV, V); primarily lowers triglycerides and very low density lipoprotein.

Dosage - Adults:
Oral: 500 mg 4 times/day; some patients may respond to lower doses

Dosing interval in renal impairment:
Clcr >50 mL/minute: Administer every 6-12 hours
Clcr 10-50 mL/minute: Administer every 12-18 hours
Clcr<10 mL/minute: Avoid use
Hemodialysis: Elimination is not enhanced via hemodialysis; supplemental dose is not necessary

Supplied: 500 mg capsule

Fenofibrate (tricor ®)

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 apo AI and apo AII.

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 α (PPARα). 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 PPARα also induces an increase in the synthesis of apoproteins AI, AII and HDL-cholesterol.

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

Fenofibrate tablets are contraindicated in patients who exhibit hypersensitivity to fenofibrate.

Fenofibrate tablets are contraindicated in patients with heptic or severe renal dysfunction, including primary biliary cirrhosis and patients with unexplained persistent liver function abnormality.

Fenofibrate tablets are contraindicated in patients with preexisting gallbladder disease

Dosage - Adults:
Hypertriglyceridemia: Initial:
Antara™: 43-130 mg/day
Lofibra™: 67 mg/day with meals, up to 200 mg/day
TriCor®: 48 mg/day, up to 145 mg/day
Previously dosed as 54 mg/day with meals (up to 160 mg/day) using the old tablet formulation

Hypercholesterolemia or mixed hyperlipidemia: Early:
Antara™: 130 mg/day
Lofibra™: 200 mg/day with meals
TriCor®: 145 mg/day
Previously dosed as 160 mg/day with meals using the old tablet formulation

Elderly: Initial: 43 mg/day (Antara™) or 67 mg/day (Lofibra™) or 48 mg/day (TriCor®)

Dosage adjustment/interval in renal impairment: Use caution in dosage adjustment. Monitor renal function and lipid panel before adjusting. Decrease dose or increase dosing interval for patients with renal failure: Initial: 43 mg/day(Antara™) or 67 mg/day (Lofibra™) or 48 mg/day (TriCor®)

Hemodialysis has no effect on removal of fenofibric acid from the plasma.

Capsule [micronized]
Antara™: 43 mg, 87 mg, 130 mg
Lofibra™: 67 mg, 134 mg, 200 mg

TriCor®: 54 mg [DSC], 160 mg [DSC]
TriCor® [new formulation]: 48 mg, 145 mg

Gemfibrozil (lopid ®) 

Gemfibrozil is a lipid regulating agent which decreases serum triglycerides and very low density lipoprotein (VLDL) cholesterol, and increases high density lipoprotein (HDL) cholesterol. While modest decreases in total and low density lipoprotein (LDL) cholesterol may be observed with gemfibrozil therapy, treatment of patients with elevated triglycerides due to Type IV hyperlipoproteinemia often results in a rise in LDL-cholesterol. LDL-cholesterol levels in Type IIb patients with elevations of both serum LDL-cholesterol and triglycerides are, in general, minimally affected by gemfibrozil treatment; however, gemfibrozil usually raises HDL-cholesterol significantly in this group. Gemfibrozil increases levels of high density lipoprotein (HDL) subfractions HDL2 and HDL3, as well as apolipoproteins AI and AII. Epidemiological studies have shown that both low HDL-cholesterol and high LDL-cholesterol are independent risk factors for coronary heart disease

Dosage - Adults: Oral: 1200 mg/day in 2 divided doses, 30 minutes before breakfast and dinner
Hemodialysis: Not removed by hemodialysis; supplemental dose is not necessary

Tablet [film coated]: 600 mg



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