FENOFIBRATE HUP

Fenofibrate is a fibric acid derivative like clofibrate and gemfibrozil.

Fenofibrate is used to treat primary hypercholesterolemia, mixed dyslipidemia, severe hypertriglyceridemia. 11, 12 Fenofibrate was granted FDA approval on 31 December 1993.

Fenofibrate is indicated as adjunctive therapy to diet: 14 To reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL) To reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when the use of recommended LDL-C lowering therapy is not possible

Fenofibrate is a fibrate that activates peroxisome proliferator activated receptor alpha (PPARα) to alter lipid metabolism and treat primary hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia. 8, 11, 12 Fenofibrate requires once daily dosing and has a half life of 19-27 hours so its duration of action is long. 3, 11, 12 Fenofibrate capsules are given at a dose of 50-150 mg daily so the therapeutic index is wide.

Patients should be counselled about the risk of rhabdomyolysis, myopathy, and cholelithiasis when taking fibrates. 11, 12.

A single 300 mg oral dose of fenofibrate reaches a C max of 6-9.5 mg/L with a T max of 4-6h in healthy, fasting volunteers.

The volume of distribution of fenofibrate is 0.89 L/kg, 4 and can be as high as 60 L.

Fenofibrate is completely hydrolyzed by liver carboxylesterase to fenofibric acid. 6, 11, 12 Fenofibric acid is either glucuronidated or has its carbonyl group reduced to a benzhydrol that is then glucuronidated. 11, 12 Glucuronidation of fenofibrate metabolites is mediated by UGT1A9.

Reduction of the carbonyl group is primarily mediated by CBR1 and minorly by AKR1C1, AKR1C2, AKR1C3, and AKR1B1.

Hover over products below to view reaction partners Fenofibrate Fenofibric acid Reduced Fenofibric Acid Reduced Fenofibric Acid Glucuronide Fenofibryl Glucuronide.

5-25% of a dose of fenofibrate is eliminated in the feces, while 60-88% is eliminated in the urine. 2, 11, 12 70-75% of the dose recovered in the urine is in the form of fenofibryl glucuronide and 16% as fenofibric acid.

Fenofibric acid, the active metabolite of fenofibrate, has a half life of 23 hours. 11, 12 Fenofibrate has a half life of 19-27 hours in healthy subjects and up to 143 hours in patients with renal failure.

The oral clearance of fenofibrate is 1.1 L/h in young adults and 1.2 L/h in the elderly. 11, 12.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

The oral

LD in rats is >2 g/kg and in mice is 1600 mg/kg.

TDLO in rats is 9 mg/kg.

Treat patients with supportive care including monitoring of vital signs and observing clinical status. 11, 12 Recent overdose may be treated with inducing vomiting or gastric lavage. 11, 12 Due to fenofibrate's extensive protein binding, hemodialysis is not expected to be useful. 2, 11, 12.

Severe renal dysfunction, including dialysis patients.

Active liver disease.

Gallbladder disease.

Known hypersensitivity to fenofibrate.

Nursing mothers.

Fenofibrate is contraindicated in: patients with severe renal impairment, including those receiving dialysis. patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities. patients with preexisting gallbladder disease. nursing mothers patients with known hypersensitivity to fenofibrate or fenofibric acid.

Primary hypercholesterolemia or mixed dyslipidemia

Initial dose of 160 mg once daily.

Severe hypertriglyceridemia

Initial dose of to 160 mg once daily.

Maximum dose is 160 mg.

Renally impaired patients

Initial dose of 54 mg once daily.

Geriatric patients

Select the dose on the basis of renal function.

Should be given with meals. 2.1 General Considerations Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablet USP, and should continue this diet during treatment with fenofibrate tablet USP.

Fenofibrate tablets

USP should be given with meals, thereby optimizing the bioavailability of the medication.

The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality.

Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy.

Physical exercise can be an important ancillary measure.

Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated.

Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia.

In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia.

Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate tablet USP if lipid levels fall significantly below the targeted range.

Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg once daily. 2.2 Primary Hypercholesterolemia or Mixed Dyslipidemia The initial dose of fenofibrate tablet USP is 160 mg once daily. 2.3 Severe Hypertriglyceridemia The initial dose is to 160 mg per day. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at to 8 week intervals.

The maximum dose is 160 mg once daily. 2.4 Impaired Renal Function Treatment with fenofibrate tablet USP should be initiated at a dose of 54 mg per day in patients having mild to moderately impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose.

The use of fenofibrate tablet

USP should be avoided in patients with severe renal impairment. 2.5 Geriatric Patients Dose selection for the elderly should be made on the basis of renal function.

50090-5854 NDC: 50090-5854-0 30 TABLET in a BOTTLE NDC: 50090-5854-1 90 TABLET in a BOTTLE.

Limited available data with fenofibrate use in pregnant women are insufficient to determine a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

In animal reproduction studies, no evidence of embryo-fetal toxicity was observed with oral administration of fenofibrate in rats and rabbits during organogenesis at doses less than or equivalent to the maximum recommended clinical dose of 160 mg daily, based on body surface area (mg/m 2 ).

Adverse reproductive outcomes occurred at higher doses in the presence of maternal toxicity.

Fenofibrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20%, respectively.

In pregnant rats given oral dietary doses of 14, 127, and 361 mg/kg/day from gestation day to 15 during the period of organogenesis, no adverse developmental findings were observed at 14 mg/kg/day (less than the clinical exposure at the maximum recommended human dose [MRHD] of 300 mg fenofibrate daily, equivalent to 160 mg fenofibrate tablets daily, based on body surface area comparisons).

Increased fetal skeletal malformations were observed at maternally toxic doses (361 mg/kg/day, corresponding to 12 times the clinical exposure at the MRHD) that significantly suppressed maternal body weight gain.

In pregnant rabbits given oral gavage doses of 15, 150, and 300 mg/kg/day from gestation day to 18 during the period of organogenesis and allowed to deliver, no adverse developmental findings were observed at 15 mg/kg/day (a dose that approximates the clinical exposure at the MRHD, based on body surface area comparisons).

Aborted litters were observed at maternally toxic doses (≥ 150 mg/kg/day, corresponding to ≥ 10 times the clinical exposure at the MRHD) that suppressed maternal body weight gain.

In pregnant rats given oral dietary doses of 15, 75, and 300 mg/kg/day from gestation day 15 through lactation day 21 (weaning), no adverse developmental effects were observed at 15 mg/kg/day (less than the clinical exposure at the MRHD, based on body surface area comparisons), despite maternal toxicity (decreased weight gain).

Post-implantation loss was observed at ≥ 75 mg/kg/day (≥ 2 times the clinical exposure at the MRHD) in the presence of maternal toxicity (decreased weight gain).

Decreased pup survival was noted at 300 mg/kg/day (10 times the clinical exposure at the MRHD), which was associated with decreased maternal body weight gain/maternal neglect.

Safety and effectiveness have not been established in pediatric patients.

Fenofibric acid is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.

Fenofibric acid exposure is not influenced by age.

Since elderly patients have a higher incidence of renal impairment, dose selection for the elderly should be made on the basis of renal function.

Elderly patients with normal renal function should require no dose modifications.

Consider monitoring renal function in elderly patients taking fenofibrate.