FENOFIBRATE - fenofibrate tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
FENOFIBRATE (UNII: U202363UOS) (FENOFIBRIC ACID - UNII:BGF9MN2HU1)
Available from:
Bryant Ranch Prepack
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Fenofibrate tablets, USP are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate tablets, USP are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacologic intervention. Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibrate therapy on reducing this risk has not been adequately studied. Fenofibrate at a dose equivalent to 160 mg of fenofibrate tablets was not shown to reduce coronary heart disease morbidity and mortality in a large, randomized controlled trial of patients wit
Product summary:
Product: 71335-1286 NDC: 71335-1286-1 30 TABLET in a BOTTLE NDC: 71335-1286-2 90 TABLET in a BOTTLE NDC: 71335-1286-3 60 TABLET in a BOTTLE NDC: 71335-1286-4 28 TABLET in a BOTTLE NDC: 71335-1286-5 100 TABLET in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
71335-1286-1, 71335-1286-2, 71335-1286-3, 71335-1286-4, 71335-1286-5

FENOFIBRATE - fenofibrate tablet

Bryant Ranch Prepack

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use FENOFIBRATE TABLETS safely and

effectively. See full prescribing information for FENOFIBRATE TABLETS.

FENOFIBRATE tablets, for oral use

Initial U.S. Approval: 1993

RECENT MAJOR CHANGES

Warnings and Precautions, Hypersensitivity Reactions (5.9) 05/2018

INDICATIONS AND USAGE

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as an adjunct to diet:

To reduce elevated LDL-C, Total-C, TG and Apo B, and to increase HDL-C in adult patients with primary

hypercholesterolemia or mixed dyslipidemia (1.1).

For treatment of adult patients with severe hypertriglyceridemia (1.2).

Limitations of Use: Fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in patients with

type 2 diabetes mellitus (5.1).

DOSAGE AND ADMINISTRATION

Primary hypercholesterolemia or mixed dyslipidemia: Initial dose of 160 mg once daily (2.2).

Severe hypertriglyceridemia: Initial dose of 54 mg to 160 mg once daily. Maximum dose is 160 mg (2.3).

Renally impaired patients: Initial dose of 54 mg once daily (2.4).

Geriatric patients: Select the dose on the basis of renal function (2.5).

Should be given with meals (2.1).

DOSAGE FORMS AND STRENGTHS

Oral Tablets: 54 mg and 160 mg (3).

CONTRAINDICATIONS

Severe renal dysfunction, including dialysis patients (4,8.6, 12.3).

Active liver disease (4, 5.3).

Gallbladder disease (4, 5.5).

Known hypersensitivity to fenofibrate (4).

Nursing mothers (4, 8.2).

WARNINGS AND PRECAUTIONS

Myopathy and rhabdomyolysis have been reported in patients taking fenofibrate. Risks are increased during co-

administration with a statin (with a significantly higher rate observed for gemfibrozil), particularly in elderly patients and

patients with diabetes, renal failure, or hypothyroidism (5.2).

Fenofibrate can increase serum transaminases. Monitor liver tests, including ALT, periodically during therapy (5.3).

Fenofibrate can reversibly increase serum creatinine levels (5.4). Monitor renal function periodically in patients with

renal impairment (8.6).

Fenofibrate increases cholesterol excretion into the bile, leading to risk of cholelithiasis. If cholelithiasis is suspected,

gallbladder studies are indicated (5.5).

Use caution in concomitant treatment with oral coumarin anticoagulants. Adjust the dosage of coumarin anticoagulant to

maintain the prothrombin time/INR at the desired level to prevent bleeding complications (5.6).

Acute hypersensitivity reactions, including anaphylaxis and angioedema, and delayed hypersensitivity reactions,

including severe cutaneous adverse drug reactions have been reported postmarketing. Some cases were life-

threatening and required emergency treatment. Discontinue fenofibrate and treat patients appropriately if reactions

occur (5.9).

ADVERSE REACTIONS

Adverse reactions > 2% and at least 1% greater than placebo: Abnormal liver tests, increased AST, increased ALT,

increased CPK, and rhinitis (6).

To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc. at 855-664-7744 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Coumarin anticoagulants: (7.1).

Immunosuppressants: (7.2).

Bile acid resins: (7.3).

USE IN SPECIFIC POPULATIONS

Geriatric Use: Determine dose selection based on renal function (8.5).

Renal Impairment: Avoid use in severe renal impairment patients. Dose reduction is required in mild to moderate renal

impairment patients (8.6).

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 8/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Primary Hypercholesterolemia or Mixed Dyslipidemia

1.2 Severe Hypertriglyceridemia

1.3 Important Limitations of Use

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations

2.2 Primary Hypercholesterolemia or Mixed Dyslipidemia

2.3 Severe Hypertriglyceridemia

2.4 Impaired Renal Function

2.5 Geriatric Patients

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Mortality and Coronary Heart Disease Morbidity

5.2 Skeletal Muscle

5.3 Liver Function

5.4 Serum Creatinine

5.5 Cholelithiasis

5.6 Coumarin Anticoagulants

5.7 Pancreatitis

5.8 Hematologic Changes

5.9 Hypersensitivity Reactions

5.10 Venothromboembolic Disease

5.11 Paradoxical Decreases in HDL Cholesterol Levels

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Coumarin Anticoagulants

7.2 Immunosuppressants

7.3 Bile Acid Binding Resins

7.4 Colchicine

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

14 CLINICAL STUDIES

14.1 Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed

Dyslipidemia

14.2 Severe Hypertriglyceridemia

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Primary Hypercholesterolemia or Mixed Dyslipidemia

Fenofibrate tablets, USP are indicated as adjunctive therapy to diet to reduce elevated low-density

lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo

B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary

hypercholesterolemia or mixed dyslipidemia.

1.2 Severe Hypertriglyceridemia

Fenofibrate tablets, USP are also indicated as adjunctive therapy to diet for treatment of adult patients

with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting

chylomicronemia will usually obviate the need for pharmacologic intervention.

Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of

developing pancreatitis. The effect of fenofibrate therapy on reducing this risk has not been adequately

studied.

1.3 Important Limitations of Use

Fenofibrate at a dose equivalent to 160 mg of fenofibrate tablets was not shown to reduce coronary

heart disease morbidity and mortality in a large, randomized controlled trial of patients with type 2

diabetes mellitus [see Warnings and Precautions (5.1)].

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablets, and

should continue this diet during treatment with fenofibrate tablets. Fenofibrate tablets should be given

with meals, thereby optimizing the bioavailability of the medication.

Sections or subsections omitted from the full prescribing information are not listed.

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 tablets 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 tablets is 160 mg once daily.

2.3 Severe Hypertriglyceridemia

The initial dose is 54 mg to 160 mg per day. Dosage should be individualized according to patient

response, and should be adjusted if necessary following repeat lipid determinations at 4 weeks to 8

weeks intervals. The maximum dose is 160 mg once daily.

2.4 Impaired Renal Function

Treatment with fenofibrate tablets 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 tablets should be avoided in patients with

severe renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.5 Geriatric Patients

Dose selection for the elderly should be made on the basis of renal function [see Use in Specific

Populations (8.5)].

3 DOSAGE FORMS AND STRENGTHS

54 mg: Light yellow to yellow colored, round-shaped, film-coated tablets debossed "FN1" on one

side and plain on other side.

160 mg: White to off-white colored, oval-shaped, film-coated tablets debossed "FN2" on one side

and plain on other side.

4 CONTRAINDICATIONS

Fenofibrate is contraindicated in:

patients with severe renal impairment, including those receiving dialysis [see Clinical Pharmacology

(12.3)].

patients with active liver disease, including those with primary biliary cirrhosis and unexplained

persistent liver function abnormalities [see Warnings and Precautions (5.3)].

patients with preexisting gallbladder disease [see Warnings and Precautions (5.5)].

nursing mothers [see Use in Specific Populations (8.2)]

patients with known hypersensitivity to fenofibrate or fenofibric acid [see Warnings and Precautions

(5.9)].

5 WARNINGS AND PRECAUTIONS

5.1 Mortality and Coronary Heart Disease Morbidity

The effect of fenofibrate on coronary heart disease morbidity and mortality and non-cardiovascular

mortality has not been established.

The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial was a randomized

placebo-controlled study of 5,518 patients with type 2 diabetes mellitus on background statin therapy

treated with fenofibrate. The mean duration of follow-up was 4.7 years. Fenofibrate plus statin

combination therapy showed a non-significant 8% relative risk reduction in the primary outcome of

major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal

stroke, and cardiovascular disease death (hazard ratio [HR] 0.92, 95% CI 0.79- 1.08) (p=0.32) as

compared to statin monotherapy. In a gender subgroup analysis, the hazard ratio for MACE in men

receiving combination therapy versus statin monotherapy was 0.82 (95% CI 0.69-0.99), and the hazard

ratio for MACE in women receiving combination therapy versus statin monotherapy was 1.38 (95% CI

0.98-1.94) (interaction p=0.01). The clinical significance of this subgroup finding is unclear.

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized,

placebo-controlled study of 9,795 patients with type 2 diabetes mellitus treated with fenofibrate.

Fenofibrate demonstrated a non-significant 11% relative reduction in the primary outcome of coronary

heart disease events (hazard ratio [HR] 0.89, 95% CI 0.75-1.05, p=0.16) and a significant 11% reduction

in the secondary outcome of total cardiovascular disease events (HR 0.89 [0.80-0.99], p=0.04). There

was a non-significant 11% (HR 1.11 [0.95, 1.29], p=0.18) and 19% (HR 1.19 [0.90, 1.57], p=0.22)

increase in total and coronary heart disease mortality, respectively, with fenofibrate as compared to

placebo.

Because of chemical, pharmacological, and clinical similarities between fenofibrate tablets, clofibrate,

and gemfibrozil, the adverse findings in 4 large randomized, placebo-controlled clinical studies with

these other fibrate drugs may also apply to fenofibrate.

In the Coronary Drug Project, a large study of post myocardial infarction of patients treated for 5 years

with clofibrate, there was no difference in mortality seen between the clofibrate group and the placebo

group. There was however, a difference in the rate of cholelithiasis and cholecystitis requiring

surgery between the two groups (3.0% vs. 1.8%).

In a study conducted by the World Health Organization (WHO), 5,000 subjects without known coronary

artery disease were treated with placebo or clofibrate for 5 years and followed for an additional one

year. There was a statistically significant, higher age - adjusted all-cause mortality in the clofibrate

group compared with the placebo group (5.70% vs. 3.96%, p = < 0.01). Excess mortality was due to a

33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications,

and pancreatitis. This appeared to confirm the higher risk of gallbladder disease seen in clofibrate-

treated patients studied in the Coronary Drug Project.

The Helsinki Heart Study was a large (n=4,081) study of middle-aged men without a history of

coronary artery disease. Subjects received either placebo or gemfibrozil for 5 years, with a 3.5 year

open extension afterward. Total mortality was numerically higher in the gemfibrozil randomization

group but did not achieve statistical significance (p = 0.19, 95% confidence interval for relative risk

G:P = .91-1.64). Although cancer deaths trended higher in the gemfibrozil group (p = 0.11), cancers

(excluding basal cell carcinoma) were diagnosed with equal frequency in both study groups. Due to the

limited size of the study, the relative risk of death from any cause was not shown to be different than that

seen in the 9 year follow-up data from World Health Organization study (RR=1.29).

A secondary prevention component of the Helsinki Heart Study enrolled middle-aged men excluded

from the primary prevention study because of known or suspected coronary heart disease. Subjects

received gemfibrozil or placebo for 5 years. Although cardiac deaths trended higher in the gemfibrozil

group, this was not statistically significant (hazard ratio 2.2, 95% confidence interval: 0.94-5.05). The

rate of gallbladder surgery was not statistically significant between study groups, but did trend higher in

the gemfibrozil group, (1.9% vs. 0.3%, p = 0.07).

5.2 Skeletal Muscle

Fibrates increase the risk for myopathy and have been associated with rhabdomyolysis. The risk for

serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal

insufficiency, or hypothyroidism.

Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness,

and/or marked elevations of creatine phosphokinase (CPK) levels.

Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness,

particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting

these symptoms, and fenofibrate therapy should be discontinued if markedly elevated CPK levels occur

or myopathy/myositis is suspected or diagnosed.

Data from observational studies indicate that the risk for rhabdomyolysis is increased when fibrates, in

particular gemfibrozil, are co-administered with an HMG-CoA reductase inhibitor (statin). The

combination should be avoided unless the benefit of further alterations in lipid levels is likely to

outweigh the increased risk of this drug combination [see Clinical Pharmacology (12.3)].

Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered

with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine [see

Drug Interactions (7.4)].

5.3 Liver Function

Fenofibrate at doses equivalent to 107 mg to 160 mg fenofibrate per day has been associated with

increases in serum transaminases [AST (SGOT) or ALT (SGPT)]. In a pooled analysis of 10 placebo-

controlled trials, increases to > 3 times the upper limit of normal occurred in 5.3% of patients taking

fenofibrate versus 1.1% of patients treated with placebo.

When transaminase determinations were followed either after discontinuation of treatment or during

continued treatment, a return to normal limits was usually observed. The incidence of increases in

transaminases related to fenofibrate therapy appear to be dose related. In an 8-week dose-ranging study,

the incidence of ALT or AST elevations to at least three times the upper limit of normal was 13% in

patients receiving dosages equivalent to 107 mg to 160 mg fenofibrate per day and was 0% in those

receiving dosages equivalent to 54 mg or less fenofibrate per day, or placebo. Hepatocellular, chronic

active and cholestatic hepatitis associated with fenofibrate therapy have been reported after exposures

of weeks to several years. In extremely rare cases, cirrhosis has been reported in association with

chronic active hepatitis.

Baseline and regular periodic monitoring of liver function, including serum ALT (SGPT) should be

performed for the duration of therapy with fenofibrate, and therapy discontinued if enzyme levels

persist above three times the normal limit.

5.4 Serum Creatinine

Elevations in serum creatinine have been reported in patients on fenofibrate. These elevations tend to

return to baseline following discontinuation of fenofibrate. The clinical significance of these

observations is unknown. Monitor renal function in patients with renal impairment taking fenofibrate.

Renal monitoring should also be considered for patients taking fenofibrate at risk for renal insufficiency

such as the elderly and patients with diabetes.

5.5 Cholelithiasis

Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the bile, leading to

cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Fenofibrate therapy

should be discontinued if gallstones are found.

5.6 Coumarin Anticoagulants

Caution should be exercised when coumarin anticoagulants are given in conjunction with fenofibrate

because of the potentiation of coumarin-type anticoagulant effects in prolonging the Prothrombin

Time/International Normalized Ratio (PT/INR). To prevent bleeding complications, frequent monitoring

of PT/INR and dose adjustment of the anticoagulant are recommended until PT/INR has stabilized [see

Drug Interactions (7.1)].

5.7 Pancreatitis

Pancreatitis has been reported in patients taking fenofibrate, gemfibrozil, and clofibrate. This

occurrence may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct

drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with

obstruction of the common bile duct.

5.8 Hematologic Changes

Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in

patients following initiation of fenofibrate therapy. However, these levels stabilize during long-term

administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with

fenofibrate. Periodic monitoring of red and white blood cell counts are recommended during the first

12 months of fenofibrate administration.

5.9 Hypersensitivity Reactions

Acute Hypersensitivity

Anaphylaxis and angioedema have been reported postmarketing with fenofibrate. In some cases,

reactions were life-threatening and required emergency treatment. If a patient develops signs or

symptoms of an acute hypersensitivity reaction, advise them to seek immediate medical attention and

discontinue fenofibrate.

Delayed Hypersensitivity

Severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome, toxic

epidermal necrolysis, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have

been reported postmarketing, occurring days to weeks after initiation of fenofibrate. The cases of

DRESS were associated with cutaneous reactions (such as rash or exfoliative dermatitis) and a

combination of eosinophilia, fever, systemic organ involvement (renal, hepatic, or respiratory).

Discontinue fenofibrate and treat patients appropriately if SCAR is suspected.

5.10 Venothromboembolic Disease

In the FIELD trial, pulmonary embolus (PE) and deep vein thrombosis (DVT) were observed at higher

rates in the fenofibrate- than the placebo-treated group. Of 9,795 patients enrolled in FIELD, there were

4,900 in the placebo group and 4,895 in the fenofibrate group. For DVT, there were 48 events (1%) in

the placebo group and 67 (1%) in the fenofibrate group (p = 0.074); and for PE, there were 32 (0.7%)

events in the placebo group and 53 (1%) in the fenofibrate group (p = 0.022).

In the Coronary Drug Project, a higher proportion of the clofibrate group experienced definite or

suspected fatal or nonfatal pulmonary embolism or thrombophlebitis than the placebo group (5.2% vs.

3.3% at five years; p < 0.01).

5.11 Paradoxical Decreases in HDL Cholesterol Levels

There have been postmarketing and clinical trial reports of severe decreases in HDL cholesterol levels

(as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibrate therapy. The

decrease in HDL-C is mirrored by a decrease in apolipoprotein A1. This decrease has been reported to

occur within 2 weeks to years after initiation of fibrate therapy. The HDL-C levels remain depressed

until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is rapid and

sustained. The clinical significance of this decrease in HDL-C is unknown. It is recommended that

HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely

depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level

monitored until it has returned to baseline, and fibrate therapy should not be re-initiated.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates

observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of

another drug and may not reflect the rates observed in practice.

Adverse events reported by 2% or more of patients treated with fenofibrate (and greater than placebo)

during the double-blind, placebo-controlled trials, regardless of causality, are listed in Table 1 below.

Adverse events led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in

3.0% treated with placebo. Increases in liver function tests were the most frequent events, causing

discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.

Table 1: Adverse Reactions Reported by 2% or More of Patients Treated with Fenofibrate and

Greater than Placebo During the Double-Blind, Placebo Controlled Trials

BODY SYSTEM

Adverse Reaction

Fenofibrate*

(N = 439)

Placebo

(N = 365)

BODY AS A WHOLE

Abdominal Pain

4.6%

4.4%

Back Pain

3.4%

2.5%

Headache

3.2%

2.7%

DIGESTIVE

Nausea

2.3%

1.9%

Constipation

2.1%

1.4%

METABOLIC AND NUTRITIONAL DISORDERS

Abnormal Liver Function Tests

7.5%

1.4%

Increased ALT

3.0%

1.6%

Increased CPK

3.0%

1.4%

Increased AST

3.4%

0.5%

RESPIRATORY

Respiratory Disorder

6.2%

5.5%

Rhinitis

2.3%

1.1%

* Dosage equivalent to 160 mg Fenofibrate.

** Significantly different from Placebo.

Urticaria was seen in 1.1% vs. 0%, and rash in 1.4% vs. 0.8% of fenofibrate and placebo patients

respectively in controlled trials.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of fenofibrate. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure: myalgia,

rhabdomyolysis, pancreatitis, acute renal failure, muscle spasm, hepatitis, cirrhosis, anemia, arthralgia,

decreases in hemoglobin, decreases in hematocrit, white blood cell decreases, asthenia, severely

depressed HDL-cholesterol levels, and interstitial lung disease. Photosensitivity reactions have

occurred days to months after initiation; in some of these cases, patients reported a prior

photosensitivity reaction to ketoprofen.

7 DRUG INTERACTIONS

7.1 Coumarin Anticoagulants

Potentiation of coumarin-type anticoagulant effects has been observed with prolongation of the PT/INR.

Caution should be exercised when coumarin anticoagulants are given in conjunction with fenofibrate.

The dosage of the anticoagulants should be reduced to maintain the PT/INR at the desired level to

prevent bleeding complications. Frequent PT/INR determinations are advisable until it has been

definitely determined that the PT/INR has stabilized [see Warnings and Precautions (5.6)].

7.2 Immunosuppressants

Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in

creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination

route of fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration

of renal function. The benefits and risks of using fenofibrate tablets with immunosuppressants and other

potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed

and renal function monitored.

7.3 Bile Acid Binding Resins

Since bile acid binding resins may bind other drugs given concurrently, patients should take fenofibrate

at least 1 hour before or 4 hours to 6 hours after a bile acid binding resin to avoid impeding its

absorption.

7.4 Colchicine

Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered

with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

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 ). Adverse

reproductive outcomes occurred at higher doses in the presence of maternal toxicity (see Data).

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 2-4% and 15-20%, respectively.

Data

Animal Data

In pregnant rats given oral dietary doses of 14 mg/kg/day, 127 mg/kg/day, and 361 mg/kg/day from

gestation day 6 to day 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 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 mg/kg/day, 150 mg/kg/day, and 300 mg/kg/day from

gestation day 6 to day 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 mg/kg/day, 75 mg/kg/day, 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.

8.2 Lactation

Risk Summary

There is no available information on the presence of fenofibrate in human milk, effects of the drug on

the breastfed infant, or the effects on milk production. Fenofibrate is present in the milk of rats, and is

therefore likely to be present in human milk. Because of the potential for serious adverse reactions in

breastfed infants, such as disruption of infant lipid metabolism, women should not breastfeed during

treatment with fenofibrate and for 5 days after the final dose [see Contraindications (4)].

8.4 Pediatric Use

Safety and effectiveness have not been established in pediatric patients.

8.5 Geriatric Use

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 [see Dosage and Administration (2.5) and

Clinical Pharmacology (12.3)]. Elderly patients with normal renal function should require no dose

modifications. Consider monitoring renal function in elderly patients taking fenofibrate.

8.6 Renal Impairment

The use of fenofibrate should be avoided in patients who have severe renal impairment [see

Contraindications (4)]. Dose reduction is required in patients with mild to moderate renal impairment [see

Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. Monitoring renal function in patients

with renal impairment is recommended.

8.7 Hepatic Impairment

The use of fenofibrate has not been evaluated in subjects with hepatic impairment [see Contraindications

(4) and Clinical Pharmacology (12.3)].

10 OVERDOSAGE

There is no specific treatment for overdose with fenofibrate. General supportive care of the patient is

indicated, including monitoring of vital signs and observation of clinical status, should an overdose

occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage;

usual precautions should be observed to maintain the airway. Because fenofibric acid is highly bound to

plasma proteins, hemodialysis should not be considered.

11 DESCRIPTION

Fenofibrate tablets, USP, are a lipid regulating agent available as tablets for oral administration. Each

tablet contains 54 mg or 160 mg of fenofibrate, USP. The chemical name for fenofibrate, USP is 2-[4-

(4-chlorobenzoyl) phenoxy]-2-methyl-propanoic acid, 1-methylethyl ester with the following structural

formula:

The empirical formula is C

H O CI and the molecular weight is 360.83; fenofibrate, USP is

insoluble in water. The melting point is 79°C to 82°C. Fenofibrate, USP is a white solid which is stable

under ordinary conditions.

Inactive Ingredients

Each 54 mg fenofibrate tablet contains the following inactive ingredients: colloidal silicon dioxide,

croscarmellose sodium, crospovidone, iron oxide yellow, lactose monohydrate, lecithin,

microcrystalline cellulose, polyvinyl alcohol, povidone, sodium lauryl sulfate, sodium starch glycolate,

sodium stearyl fumarate, talc, titanium dioxide, xanthan gum, and D&C yellow #10 lake.

Each 160 mg fenofibrate tablet contains the following inactive ingredients: colloidal silicon dioxide,

croscarmellose sodium, crospovidone, lactose monohydrate, lecithin, microcrystalline cellulose,

polyvinyl alcohol, povidone, sodium lauryl sulfate, sodium starch glycolate, sodium stearyl fumarate,

talc, titanium dioxide, and xanthan gum.

Fenofibrate tablet meets USP Dissolution Test 3.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The active moiety 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 TG 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

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.

12.2 Pharmacodynamics

A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and apo B, an

LDL membrane complex, are associated with human atherosclerosis. Similarly, decreased levels of

HDL-C and its transport complex, apolipoprotein A (apo AI and apo AII) are associated with the

development of atherosclerosis. Epidemiologic investigations have established that cardiovascular

morbidity and mortality vary directly with the level of total-C, LDL-C, and TG, 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 apoAI and apoAII.

12.3 Pharmacokinetics

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.

Absorption

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

radiolabelled 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 6 hours to 8

hours after administration.

The absorption of fenofibrate is increased when administered with food. With fenofibrate tablets, the

extent of absorption is increased by approximately 35% under fed as compared to fasting conditions.

Distribution

Upon multiple dosing of fenofibrate, fenofibric acid steady state is achieved within 5 days. Plasma

concentrations of fenofibric acid at steady state are approximately double of those following a single

dose. Serum protein binding was approximately 99% in normal and hyperlipidemic subjects.

Metabolism

Following oral administration, fenofibrate is rapidly hydrolyzed by esterases to the active metabolite,

fenofibric acid; no unchanged fenofibrate is detected in plasma.

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 vivo metabolism data indicate that neither fenofibrate nor fenofibric acid undergo oxidative

metabolism (e.g., cytochrome P450) to a significant extent.

Elimination

After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily

fenofibric acid and fenofibric acid glucuronide. After administration of radiolabelled fenofibrate,

approximately 60% of the dose appeared in the urine and 25% was excreted in the feces.

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

Special Populations

Geriatrics

In elderly volunteers 77 years to 87 years of age, the 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 a similar dosage regimen can be used in elderly with normal renal function, without increasing

accumulation of the drug or metabolites [see Dosage and Administration (2.5) and Use in Specific

Populations (8.5)].

Pediatrics

The pharmacokinetics of fenofibrate has not been studied in pediatric populations.

Gender

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

Race

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 severe renal impairment (estimated glomerular filtration rate [eGFR] < 30

mL/min/1.73m ) showed 2.7-fold increase in exposure for fenofibric acid and increased accumulation

of fenofibric acid during chronic dosing compared to that of healthy subjects. Patients with mild to

moderate renal impairment (eGFR 30 mL/min/1.73m to 59 mL/min/1.73m ) had similar exposure but an

increase in the half-life for fenofibric acid compared to that of healthy subjects. Based on these

findings, the use of fenofibrate should be avoided in patients who have severe renal impairment and

dose reduction is required in patients having mild to moderate renal impairment [see Dosage and

Administration (2.4)].

Hepatic Impairment

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

Drug-drug Interactions

In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not

inhibitors of cytochrome (CYP) P450 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 co-administered fenofibrate or fenofibric acid on other 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

Dosage Regimen of Fenofibrate*

Changes in Fenofibric

Acid Exposure

Lipid-lowering agents

Atorvastatin

20 mg once daily for 10

days

Fenofibrate 160 mg once daily

for 10 days

↓2%

↓4%

Pravastatin

40 mg as a single dose

Fenofibrate

single dose

↓1%

↓2%

Fluvastatin

40 mg as a single dose

Fenofibrate 160 mg as a single

dose

↓2%

↓10%

Anti-diabetic agents

Glimepiride

1 mg as a single dose

Fenofibrate 145 mg

once daily

for 10 days

↑1%

↓1%

Metformin

850 mg three times daily

for 10 days

Fenofibrate 54 mg three times

daily for 10 days

↓9%

↓6%

Rosiglitazone

once

daily

days

Fenofibrate 145 mg once daily

for 14 days

↑10%

↑3%

* Plasma concentrations of fenofibric acid after administration of 54 mg and 160 mg tablets are

equivalent under fed conditions to 67 mg and 200 mg capsules, respectively. Plasma concentrations of

fenofibric acid after administration of one 145 mg tablet are equivalent under fed conditions to one 200

mg capsule.

Fenofibrate oral tablet

Fenofibrate oral micronized capsule

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

Dosage

Regimen

Fenofibrate*

Dosage

Regimen

Administered Drug

Change in Co-Administered Drug

Exposure

Analyte

Lipid-lowering agents

Fenofibrate

onceAtorvastatin, 20 mg once daily for

Atorvastatin

↓17%

daily for 10 days

10 days

Atorvastatin

↓17%

Fenofibrate 3 x 67 mg as a

single dose

Pravastatin, 40 mg as a single dose

Pravastatin

↑13%

↑13%

3α-Hydroxyl-iso-

pravastatin

↑26%

↑29%

Fenofibrate

single dose

Fluvastatin, 40 mg as a single dose

(+)-3R,

Fluvastatin

↑15%

↑16%

Anti-diabetic agents

Fenofibrate

once

daily for 10 days

Glimepiride, 1 mg as a single dose

Glimepiride

↑35%

↑18%

Fenofibrate

three

times daily for 10 days

Metformin, 850 mg three times daily

for 10 days

Metformin

↑3%

↑6%

Fenofibrate

once

daily for 14 days

Rosiglitazone, 8 mg once daily for 5

days

Rosiglitazone

↑6%

↓1%

* Plasma concentrations of fenofibric acid after administration of 54 mg and 160 mg tablets are

equivalent under fed conditions to 67 mg and 200 mg capsules, respectively. Plasma concentrations of

fenofibric acid after administration of one 145 mg tablet are equivalent under fed conditions to one 200

mg capsule.

Fenofibrate oral tablet

Fenofibrate oral micronized capsule

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

Two dietary carcinogenicity studies have been conducted in rats with fenofibrate. In the first 24-month

study, Wistar rats were dosed with fenofibrate at 10 mg/kg/day, 45 mg/kg/day, and 200 mg/kg/day,

approximately 0.3, 1, and 6 times the maximum recommended human dose (MRHD) of 300 mg

fenofibrate daily, equivalent to 160 mg fenofibrate tablets daily, based on body surface area

comparisons. At a dose of 200 mg/kg/day (at 6 times the MRHD), the incidence of liver carcinomas was

significantly increased in both sexes. A statistically significant increase in pancreatic carcinomas was

observed in males at 1 and 6 times the MRHD; an increase in pancreatic adenomas and benign testicular

interstitial cell tumors was observed at 6 times the MRHD in males. In a second 24-month rat

carcinogenicity study in a different strain of rats (Sprague-Dawley), doses of 10 mg/kg/day and 60

mg/kg/day (0.3 and 2 times the MRHD) produced significant increases in the incidence of pancreatic

acinar adenomas in both sexes and increases in testicular interstitial cell tumors in males at 2 times the

MRHD.

A 117-week carcinogenicity study was conducted in rats comparing three drugs: fenofibrate 10

mg/kg/day and 60 mg/kg/day (0.3 and 2 times the MRHD, based on body surface area comparisons),

clofibrate (400 mg/kg/day; 2 times the human dose), and gemfibrozil (250 mg/kg/day; 2 times the human

dose, based on mg/m surface area). Fenofibrate increased pancreatic acinar adenomas in both sexes.

Clofibrate increased hepatocellular carcinoma and pancreatic acinar adenomas in males and hepatic

neoplastic nodules in females. Gemfibrozil increased hepatic neoplastic nodules in males and females,

while all three drugs increased testicular interstitial cell tumors in males.

In a 21-month study in CF-1 mice, fenofibrate 10 mg/kg/day, 45 mg/kg/day, and 200 mg/kg/day

(approximately 0.2, 1, and 3 times the MRHD, based on body surface area comparisons) significantly

increased the liver carcinomas in both sexes at 3 times the MRHD. In a second 18-month study at 10

mg/kg/day, 60 mg/kg/day, and 200 mg/kg/day, fenofibrate significantly increased the liver carcinomas in

male mice and liver adenomas in female mice at 3 times the MRHD.

Electron microscopy studies have demonstrated peroxisomal proliferation following fenofibrate

administration to the rat. An adequate study to test for peroxisome proliferation in humans has not been

done, but changes in peroxisome morphology and numbers have been observed in humans after treatment

with other members of the fibrate class when liver biopsies were compared before and after treatment

in the same individual.

Fenofibrate has been demonstrated to be devoid of mutagenic potential in the following tests: Ames,

mouse lymphoma, chromosomal aberration and unscheduled DNA synthesis in primary rat hepatocytes.

In fertility studies rats were given oral dietary doses of fenofibrate, males received 61 days prior to

mating and females 15 days prior to mating through weaning which resulted in no adverse effect on

fertility at doses up to 300 mg/kg/day (10 times the MRHD, based on body surface area comparisons).

14 CLINICAL STUDIES

14.1 Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed

Dys lipidemia

The effects of fenofibrate at a dose equivalent to 160 mg fenofibrate tablets per day were 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

Treatment 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%

+11.0%

-28.9%

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).

14.2 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

mg/dL to 1,500 mg/dL, and the other TG levels of 350 mg/dL to 500 mg/dL. In patients with

hypertriglyceridemia and normal cholesterolemia with or without hyperchylomicronemia, treatment with

fenofibrate at dosages equivalent to fenofibrate 160 mg per day decreased primarily very low density

lipoprotein (VLDL) triglycerides and VLDL cholesterol. Treatment of patients with elevated

triglycerides often results in an increase of LDL-C (see Table 5).

Table 5: Effect of Fenofibrate in Patients With Severe Hypertriglyceridemia

Study 1

Placebo

Fenofibrate

Baseline

TG

levels

350 mg/dL to

499 mg/dL

N

Baseline

(Mean)

Endpoint

(Mean)

%

Change

(Mean)

N

Baseline

(Mean)

Endpoint

(Mean)

%

Change

(Mean)

T riglycerides

-0.5

-46.2*

VLDL

T riglycerides

-44.1*

Total Cholesterol

-9.1*

HDL Cholesterol

19.6*

LDL Cholesterol

14.5

VLDL Cholesterol

-44.7*

Study 2

Placebo

Fenofibrate

Baseline

TG

levels

500 mg/dL to

1,500 mg/dL

N

Baseline

(Mean)

Endpoint

(Mean)

%

Change

(Mean)

N

Baseline

(Mean)

Endpoint

(Mean)

%

Change

(Mean)

T riglycerides

-54.5*

VLDL

T riglycerides

18.7

-50.6*

Total Cholesterol

-13.8*

HDL Cholesterol

22.9*

LDL Cholesterol

-4.2

45.0*

VLDL Cholesterol

11.0

-49.4*

* = p < 0.05 vs. Placebo

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 71335-1286

NDC: 71335-1286-1 30 TABLET in a BOTTLE

NDC: 71335-1286-2 90 TABLET in a BOTTLE

NDC: 71335-1286-3 60 TABLET in a BOTTLE

NDC: 71335-1286-4 28 TABLET in a BOTTLE

NDC: 71335-1286-5 100 TABLET in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Patients should be advised:

of the potential benefits and risks of fenofibrate tablets.

not to use fenofibrate tablets if there is a known hypersensitivity to fenofibrate or fenofibric acid.

of medications that should not be taken in combination with fenofibrate tablets.

that if they are taking coumarin anticoagulants, fenofibrate tablets may increase their anti-coagulant

effect, and increased monitoring may be necessary.

to continue to follow an appropriate lipid-modifying diet while taking fenofibrate tablets.

to take fenofibrate tablets once daily with a meal at the prescribed dose, swallowing each tablet

whole.

to return to their physician’s office for routine monitoring.

to inform their physician of all medications, supplements, and herbal preparations they are taking and

any change to their medical condition. Patients should also be advised to inform their physicians

prescribing a new medication that they are taking fenofibrate tablet.

to inform their physician of any muscle pain, tenderness, or weakness; onset of abdominal pain; or

any other new symptoms.

not to breastfeed during treatment with fenofibrate and for 5 days after the final dose.

Marketed by:

Ajanta Pharma USA Inc.

Bridgewater, NJ 08807.

Made in India.

Revised: 04/2019

Fenofibrate 160mg Tablet

FENOFIBRATE

fenofibrate tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:71335-128 6 (NDC:27241-117)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

FENO FIBRATE (UNII: U20 236 3UOS) (FENOFIBRIC ACID - UNII:BGF9 MN2HU1)

FENOFIBRATE

16 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

CRO SPO VIDO NE, UNSPECIFIED (UNII: 2S78 30 E56 1)

Bryant Ranch Prepack

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

EGG PHO SPHO LIPIDS (UNII: 1Z7418 4RGV)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

PO LYVINYL ALCO HO L, UNSPECIFIED (UNII: 532B59 J9 9 0 )

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

SO DIUM STARCH GLYCO LATE TYPE A CO RN (UNII: AG9 B6 5PV6 B)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

XANTHAN GUM (UNII: TTV12P4NEE)

Product Characteristics

Color

WHITE

S core

no sco re

S hap e

OVAL

S iz e

19 mm

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:71335-128 6 -1

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 1/0 1/20 19

2

NDC:71335-128 6 -2

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 1/0 1/20 19

3

NDC:71335-128 6 -3

6 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 1/0 1/20 19

4

NDC:71335-128 6 -4

28 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 1/0 1/20 19

5

NDC:71335-128 6 -5

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 1/0 1/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA210 138

0 7/20 /20 18

Labeler -

Bryant Ranch Prepack (171714327)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Bryant Ranch Prepack

171714327

REPACK(71335-128 6 ) , RELABEL(71335-128 6 )

Revised: 8/2019

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