Fibrates

Background

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 ®)	fenofibrate (Tricor ®):
gemfibrozil (Lopid ®):

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

Mechanism of Action
Mechanism is unclear but thought to reduce cholesterol synthesis and triglyceride hepatic-vascular transference

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

Administration
Administer with meals or milk if GI upset occurs.

Supplied: 500 mg capsule

fenofibrate (Tricor ®):

INDICATIONS
Adjunct to dietary therapy for the treatment of adults with very high elevations of serum triglyceride levels (types IV and V hyperlipidemia) who are at risk of pancreatitis and who do not respond adequately to a determined dietary effort; adjunct to dietary therapy for the reduction of low density lipoprotein cholesterol (LDL-C), total cholesterol (total-C), triglycerides, and apolipoprotein B (apo B) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson types IIa and IIb)

Mechanism of Action
Fenofibric acid is believed to increase VLDL catabolism by enhancing the synthesis of lipoprotein lipase; as a result of a decrease in VLDL levels, total plasma triglycerides are reduced by 30% to 60%; modest increase in HDL occurs in some hypertriglyceridemic patients

Dosage - Adults:
Oral:
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.

Administration
6-8 weeks of therapy is required to determine efficacy.
Capsule: Administer with meals.
Tablet: May be administered with or without food.
Supplied
Capsule [micronized]
Antara™: 43 mg, 87 mg, 130 mg
Lofibra™: 67 mg, 134 mg, 200 mg

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

gemfibrozil (Lopid ®):

INDICATIONS
Treatment of hypertriglyceridemia in types IV and V hyperlipidemia for patients who are at greater risk for pancreatitis and who have not responded to dietary intervention

Mechanism of Action
The exact mechanism of action of gemfibrozil is unknown, however, several theories exist regarding the VLDL effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels; increases HDL-cholesterol; the mechanism behind HDL elevation is currently unknown

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

Supplied
Tablet [film coated]: 600 mg

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.