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Fenofibrate 40 mg/ 120 mg


Mechanism Of Action

The active metabolite of fenofibrate is fenofibric acid. The pharmacological effects of fenofibric acid in both animals and humans have been extensively studied through oral administration of fenofibrate.

The lipid-modifying 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 decrease 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 apolipoproteins 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.


Elevated levels of total-c, LDL-C, and apo B and decreased levels of HDL-C and its transport complex, Apo AI and Apo AII, are risk factors for atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-c, LDL-C, and triglycerides, and inversely with the level of HDL-C. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of cardiovascular morbidity and mortality has not been determined.

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 apolipoproteins AI and AII.


The extent and rate of absorption of fenofibric acid after administration of 150 mg fenofibrate capsules are equivalent under low-fat and high-fat fed conditions to 160 mg TriCor® tablets.

Fenofibrate is a pro-drug of the active chemical moiety fenofibric acid. Fenofibrate is converted by ester hydrolysis in the body to fenofibric acid which is the active constituent measurable in the circulation. In a bioavailability study with fenofibrate capsules 200 mg, following single-dose administration, the plasma concentration (AUC) for the parent compound fenofibrate was approximately 40 μg/mL compared to 204 μg/mL for the metabolite, fenofibric acid. In the same study, the halflife was observed to be 0.91 hrs for the parent compound versus 16.76 hrs for the metabolite.


The absolute bioavailability of fenofibrate cannot be determined as the compound is virtually insoluble in aqueous media suitable for injection. However, fenofibrate is well absorbed from the gastrointestinal tract. Following oral administration in healthy volunteers, approximately 60% of a single dose of radiolabeled fenofibrate appeared in urine, primarily as fenofibric acid and its glucuronate conjugate, and 25% was excreted in the feces. Peak plasma levels of fenofibric acid occur within approximately 5 hours after oral administration.

The absorption of fenofibrate is increased when administered with food. With fenofibrate, the extent of absorption is increased by approximately 58% and 25% under high-fat fed and low-fat fed conditions as compared to fasting conditions, respectively.

In a single dose and multiple dose bioavailability study with fenofibrate capsules 200 mg, the extent of absorption (AUC) of fenofibric acid, the principal metabolite of fenofibrate, was 42% larger at steady state compared to single-dose administration. The rate of absorption (Cmax) of fenofibric acid was 73% greater after multiple-dose than after single-dose administration.

The extent of absorption of fenofibrate capsules in terms of AUC value of fenofibric acid increased in a less than proportional manner while the rate of absorption in terms of Cmax value of fenofibric acid increased proportionally related to dose.


Upon multiple dosing of fenofibrate, fenofibric acid steady state is achieved after 5 days. Plasma concentrations of fenofibric acid at steady state are slightly more than double those following a single dose. Serum protein binding was approximately 99% in normal and hyperlipidemic subjects.


Following oral administration, fenofibrate is rapidly hydrolyzed by esterases to the active metabolite, fenofibric acid; unchanged fenofibrate is detected at low concentrations in plasma compared to fenofibric acid over most of the single dose and multiple dosing periods.

Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to a benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine.

In vitro and in vivo metabolism data indicate that neither fenofibrate nor fenofibric acid undergo oxidative metabolism (e.g., cytochrome P450) to a significant extent.


After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. After administration of radiolabeled fenofibrate, approximately 60% of the dose appeared in the urine and 25% was excreted in feces.

Fenofibric acid is eliminated with a half-life of approximately 20 hours allowing once daily dosing.


In elderly volunteers 77 to 87 years of age, the apparent oral clearance of fenofibric acid following a single oral dose of fenofibrate was 1.2 L/h, which compares to 1.1 L/h in young adults. This indicates that an equivalent dose of fenofibrate can be used in elderly subjects with normal renal function, without increasing accumulation of the drug or metabolites [see DOSAGE AND ADMINISTRATION and Use in Specific Populations].


Pharmacokinetics of fenofibrate has not been studied in pediatric patients.


No pharmacokinetic difference between males and females has been observed for fenofibrate.


The influence of race on the pharmacokinetics of fenofibrate has not been studied, however fenofibrate is not metabolized by enzymes known for exhibiting inter-ethnic variability.

Renal Impairment

The pharmacokinetics of fenofibric acid was examined in patients with mild, moderate and severe renal impairment. Patients with mild (estimated glomerular filtration rate eGFR 60- 89 ml/min/1.73m²) to moderate (eGFR 30-59 mL/min/1.73m²) renal impairment had similar exposure but an increase in the half-life for fenofibric acid was observed as compared to that of healthy subjects. Patients with severe renal impairment (eGFR < 30 mL/min/1.73m²) showed a 2.7-fold increase in exposure for fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared to that of healthy subjects. In patients with mild to moderate renal impairment, treatment with fenofibrate should be initiated at a dose of 50 mg per day, and increased only after evaluation of the effects on renal function and lipid levels at this dose. Based on these findings, the use of fenofibrate should be avoided in patients who have severe renal impairment.

Hepatic Impairment

No pharmacokinetic studies have been conducted in patients having hepatic impairment.

Drug-Drug Interactions

In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome P450 (CYP) isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C8, CYP2C19 and CYP2A6, and mild to moderate inhibitors of CYP2C9 at therapeutic concentrations.

Table 2 describes the effects of co-administered drugs on fenofibric acid systemic exposure. Table 3 describes the effects of fenofibrate on co-administered drugs.

Table 2: Effects of Co-Administered Drugs on Fenofibric Acid Systemic Exposure from Fenofibrate Administration

Co-Administered Drug Dosage Regimen of Co-Administered Drug Dos age Regimen of Fenofibrate Changes in Fenofibric Acid Exposure
AUC Cmax
Lipid-lowering agents
Atorvastatin 20 mg once daily for 10 days Fenofibrate 160 mg1 once daily for 10 days ↓2% ↓4%
Pravastatin 40 mg as a single dose Fenofibrate 3 x 67 mg2 as a single dose ↓1% ↓2%
Fluvastatin 40 mg as a single dose Fenofibrate 16 0mg1 as a single dose ↓2% ↓10%
Anti-diabetic agents
Glimepiride 1 mg as a single dose Fenofibrate 145 mg1 once daily for 10days ↑1% ↓1%
Metformin 850 mg three times daily for 10 days Fenofibrate 54 mg1 three times daily for 10 days ↓9% ↓6%
Rosiglitazone 8 mg once daily for 5days Fenofibrate 145 mg1 once daily for 14days ↑10% T3%
1TriCor (fenofibrate) oral tablet
2TriCor (fenofibrate) oral micronized capsule

Table 3: Effects of Fenofibrate on Systemic Exposure of Co-Administered Drugs

Dosage Regimen of Fenofibrate Dosage Regimen of Co-Administered Drug Change in Co-Administered Drug Exposure
Analyte AUC Cmax
Lipid-lowering agents
Fenofibrate 160 mg1 once daily for 10 days Atorvastatin, 20 mg once daily for 10 days Atorvastatin ↓17% 0%
Fenofibrate 3 x 67 mg2 as a single dose Pravastatin, 40 mg as a single dose Pravastatin ↑13% ↑13%
3α-Hydroxyl-iso- pravastatin ↑ 26% ↑ 29 %
Fenofibrate 160 mg1 as a single dose Fluvastatin, 40 mg as a single dose (+)-3R, 5S-Fluvastatin ↑5% ↑16%
Anti-diabetic agents
Fenofibrate 145 mg1 once daily for 10 days Glimepiride, 1 mg as a single dose Glimepiride ↑35% ↑18%
Fenofibrate 54 mg1 three times daily for 10 days Metformin, 850 mg three times daily for 10 days Metformin ↑3% ↑6%
Fenofibrate 145 mg1 once daily for 14 days Rosiglitazone, 8 mg once daily for 5 days Rosiglitazone ↑6% ↓1%
1TriCor (fenofibrate) oral tablet
2TriCor (fenofibrate) oral micronized capsule

Clinical Studies

Clinical trials have not been conducted with fenofibrate capsules.

Primary Hypercholesterolemia (Heterozygous Familial And Nonfamilial) And Mixed Dyslipidemia

The effects of fenofibrate at a dose equivalent to 150 mg per day of fenofibrate was assessed from four randomized, placebo-controlled, double-blind, parallel-group studies including patients with the following mean baseline lipid values: total-c 306.9 mg/dL; LDL-C 213.8 mg/dL; HDL-C 52.3 mg/dL; and triglycerides 191.0 mg/dL. Fenofibrate therapy lowered LDL-C, total-c, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C (see Table 4).

Table 4: Mean Percent Change in Lipid Parameters at End of Treatment+

T reatment Group Total-C LDL-C HDL-C TG
Pooled Cohort
Mean baseline lipid values (n=646) 306.9 mg/dL 213.8 mg/dL 52.3 mg/dL 191.0 mg/dL *
All FEN (n=361) -18.7%* -20.6%*



Placebo (n=285) -0.4% -2.2% +0.7% +7.7%
Baseline LDL-C > 160 mg/dL and TG < 150 mg/dL
Mean baseline lipid values (n=334) 307.7 mg/dL 227.7 mg/dL 58.1 mg/dL 101.7 mg/dL
All FEN (n=193) -22.4%* -31.4%* +9.8% -23.5%*
Placebo (n=141) +0.2% -2.2% +2.6% +11.7%
Baseline LDL-C > 160 mg/dL and TG ≥ 150 mg/dL
Mean baseline lipid values (n=242) 312.8 mg/dL 219.8 mg/dL 46.7 mg/dL 231.9 mg/dL
All FEN (n=126) -16.8%* -20.1%* +14.6%* -35.9%*
Placebo (n=116) -3.0% -6.6% +2.3% +0.9%
+Duration of study treatment was 3 to 6 months.
* p = < 0.05 vs. Placebo

In a subset of the subjects, measurements of apo B were conducted. Fenofibrate treatment significantly reduced apo B from baseline to endpoint as compared with placebo (-25.1% vs. 2.4%, p < 0.0001, n=213 and 143 respectively).

Severe Hypertriglyceridemia

The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients. Patients were treated for eight weeks under protocols that differed only in that one entered patients with baseline TG levels of 500 to 1500 mg/dL, and the other TG levels of 350 to 500 mg/dL. In patients with hypertriglyceridemia and normal cholesterolemia with or without hyperchylomicronemia, treatment with fenofibrate at dosages equivalent to 150 mg fenofibrate per day decreased primarily very low density lipoprotein (VLDL), triglycerides and VLDL cholesterol. Treatment of some with elevated triglycerides often results in an increase of LDL-C (see Table 5).

Table 5: Effects in Patients With Severe Hypertriglyceridemia

Study 1 Placebo Fenofibrate
Baseline TG Levels 350 to 499 mg/dL N Baseline (Mean) Endpoint (Mean) % Change (Mean) N Bas eline (Mean) Endpoint (Mean) % Change (Mean)
Triglycerides 28 449 450 -0.5 27 432 223 -46.2*
VLDL Triglycerides 19 367 350 2.7 19 350 178 -44.1*
Total Cholesterol 28 255 261 2.8 27 252 227 -9.1*
HDL Cholesterol 28 35 36 4 27 34 40 19.6*
LDL Cholesterol 28 120 129 12 27 128 137 14.5
VLDL Cholesterol 27 99 99 5.8 27 92 46 -44.7*
Study 2     Placebo     Fenofibrate  
Baseline TG Levels 500 to 1500 mg/dL N Baseline (Mean) Endpoint (Mean) % Change (Mean) N Bas eline (Mean) Endpoint (Mean) % Change (Mean)
Triglycerides 44 710 750 7.2 48 726 308 -54.5*
VLDL Triglycerides 29 537 571 18.7 33 543 205 -50.6*
Total Cholesterol 44 272 271 0.4 48 261 223 -13.8*
HDL Cholesterol 44 27 28 5.0 48 30 36 22.9*
LDL Cholesterol 42 100 90 -4.2 45 103 131 45.0*
VLDL Cholesterol 42 137 142 11.0 45 126 54 -49.4*
*=P < 0.05 vs. Placebo

The effect of fenofibrate on cardiovascular morbidity and mortality has not been determined.

Last reviewed on RxList: 10/6/2016
This monograph has been modified to include the generic and brand name in many instances.

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