NDC 42571-348 Fenofibric Acid

Fenofibric Acid

NDC Product Code 42571-348

NDC CODE: 42571-348

Proprietary Name: Fenofibric Acid What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Fenofibric Acid What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Fenofibric acid is used along with a proper diet to help lower bad cholesterol and fats (such as LDL, triglycerides) and raise good cholesterol (HDL) in the blood. It works by increasing the natural substance (enzyme) that breaks down fats in the blood. Fenofibric acid belongs to a group of drugs known as fibrates. Lowering triglycerides in people with very high triglyceride blood levels may decrease the risk of pancreas disease (pancreatitis). However, fenofibric acid might not lower your risk of a heart attack or stroke. Talk to your doctor about the risks and benefits of fenofibric acid. In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.

Product Characteristics

Color(s):
RED (C48326 - REDDISH BROWN OPAQUE CAP)
YELLOW (C48330 - YELLOW OPAQUE BODY)
BLUE (C48333 - OPAQUE CAP)
YELLOW (C48330 - OPAQUE BODY)
Shape: CAPSULE (C48336)
Size(s):
16 MM
21 MM
Imprint(s):
CDR;45
CDR;135
Score: 1

NDC Code Structure

NDC 42571-348-05

Package Description: 500 CAPSULE, DELAYED RELEASE in 1 BOTTLE

NDC 42571-348-30

Package Description: 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE

NDC 42571-348-90

Package Description: 90 CAPSULE, DELAYED RELEASE in 1 BOTTLE

NDC Product Information

Fenofibric Acid with NDC 42571-348 is a a human prescription drug product labeled by Micro Labs Limited. The generic name of Fenofibric Acid is fenofibric acid. The product's dosage form is capsule, delayed release and is administered via oral form.

Labeler Name: Micro Labs Limited

Dosage Form: Capsule, Delayed Release - A solid dosage form in which the drug is enclosed within either a hard or soft soluble container made from a suitable form of gelatin, and which releases a drug (or drugs) at a time other than promptly after administration. Enteric-coated articles are delayed release dosage forms.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Fenofibric Acid Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • FENOFIBRIC ACID 135 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • HYPROMELLOSE 2208 (15000 MPA.S) (UNII: Z78RG6M2N2)
  • HYDROXYPROPYL CELLULOSE (110000 WAMW) (UNII: 5Y0974F5PW)
  • METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A (UNII: NX76LV5T8J)
  • MICROCRYSTALLINE CELLULOSE 101 (UNII: 7T9FYH5QMK)
  • POVIDONE K30 (UNII: U725QWY32X)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)
  • TALC (UNII: 7SEV7J4R1U)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • GELATIN (UNII: 2G86QN327L)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • HYPROMELLOSE 2208 (15000 MPA.S) (UNII: Z78RG6M2N2)
  • HYDROXYPROPYL CELLULOSE (110000 WAMW) (UNII: 5Y0974F5PW)
  • METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A (UNII: NX76LV5T8J)
  • MICROCRYSTALLINE CELLULOSE 101 (UNII: 7T9FYH5QMK)
  • POVIDONE K30 (UNII: U725QWY32X)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)
  • TALC (UNII: 7SEV7J4R1U)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FD&C RED NO. 3 (UNII: PN2ZH5LOQY)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • GELATIN (UNII: 2G86QN327L)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Peroxisome Proliferator Receptor alpha Agonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Micro Labs Limited
Labeler Code: 42571
FDA Application Number: ANDA213450 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 09-01-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Fenofibric Acid Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Treatment Of Severe Hypertriglyceridemia

Fenofibric acid delayed-release capsules are indicated as adjunctive therapy to diet to reduce triglycerides (TG) in patients with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacological intervention. Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibric acid delayed-release capsules therapy on reducing this risk has not been adequately studied.

1.2 Treatment Of Primary Hypercholesterolemia Or Mixed Dyslipidemia

Fenofibric acid delayed-release capsules are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), triglycerides (TG), and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDLC) in patients with primary hypercholesterolemia or mixed dyslipidemia.

2.1 General Considerations

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibric acid delayed-release capsules and should continue this diet during treatment. Fenofibric acid delayed-release capsules can be taken without regard to meals. Patients should be advised to swallow fenofibric acid delayed-release capsules whole. Do not open, crush, dissolve, or chew capsules. Serum lipids should be monitored periodically.

2.2 Severe Hypertriglyceridemia

The initial dose of fenofibric acid delayed-release capsules


are 45 to 135 mg once daily. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 135 mg once daily.

2.3 Primary Hypercholesterolemia Or Mixed Dyslipidemia

The dose of fenofibric acid delayed-release capsule is 135 mg once daily.

2.4 Impaired Renal Function

Treatment with fenofibric acid delayed-release capsules should be initiated at a dose of 45 mg once daily in patients with mild to moderate renal impairment and should only be increased after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibric acid delayed-release capsules should be avoided in patients with severely impaired renal function


[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

  • Fenofibric Acid Delayed-Release Capsules 45 mg:Reddish brown opaque cap imprinted with “CDR”, yellow opaque body imprinted with “45”, size “3”, hard gelatin capsule contains 4 white to off-white, round, biconvex delayed release mini tablets.
  • Fenofibric Acid Delayed-Release Capsules 135 mg:Blue opaque cap imprinted with “CDR” and yellow opaque body imprinted with “135 mg”, size “0”, hard gelatin capsule contains 12 white to off-white, round, biconvex delayed release mini tablets.

4 Contraindications

  • Fenofibric acid delayed-release capsules are 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 hypersensitivity to fenofibric acid or fenofibrate [see
  • Warnings and Precautions ( 5.9 )].

5.1 Mortality And Coronary Heart Disease Morbidity

The effect of fenofibric acid delayed-release capsules on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. Because of similarities between fenofibric acid delayed-release capsules and fenofibrate, clofibrate, and gemfibrozil, the findings in the following large randomized, placebo-controlled clinical studies with these fibrate drugs may also apply to fenofibric acid delayed-release capsules.The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial was a randomized placebo-controlled study of 5518 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 to1.08) (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 to 0.99), and the hazard ratio for MACE in women receiving combination therapy versus statin monotherapy was 1.38 (95% CI 0.98 to 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 9795 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 to 1.05, p = 0.16) and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 [0.80 to 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.In the Coronary Drug Project, a large study of post-myocardial infarction 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% vs. 1.8%).In a study conducted by the World Health Organization (WHO), 5000 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 = 4081) 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 = 0.91 to 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 WHO 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 to 5.05).

5.2 Skeletal Muscle

Fibrates increase the risk of myositis or 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 failure, or hypothyroidism.Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of CPK levels. Patients should promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and fenofibric acid delayed-release capsules should be discontinued if markedly elevated CPK levels occur or myopathy or myositis is suspected or diagnosed.Data from observational studies suggest that the risk for rhabdomyolysis is increased when fibrates are co-administered with a statin.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

Fenofibric acid delayed-release capsules at a dose of 135 mg once daily has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)]. In a pooled analysis of three 12-week, double- blind, controlled studies of fenofibric acid delayed-release capsules, increases in ALT and AST to > 3 times the upper limit of normal on two consecutive occasions occurred in 1.9% and 0.2%, respectively, of patients receiving fenofibric acid delayed-release capsules without other lipid-altering drugs. Increases in ALT and/or AST were not accompanied by increases in bilirubin or clinically significant increases in alkaline phosphatase.In a pooled analysis of 10 placebo-controlled trials of fenofibrate, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate versus 1.1% of patients treated with placebo. The incidence of increases in transaminases observed with fenofibrate therapy may be dose related. In an 8-week dose-ranging study of fenofibrate in hypertriglyceridemia, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 90 mg to 135 mg fenofibric acid delayed-release capsules once daily and was 0% in those receiving dosages equivalent to 45 mg fenofibric acid delayed-release capsules once daily or less, or placebo. Hepatocellular, chronic active, and cholestatic hepatitis observed 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 monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with fenofibric acid delayed-release capsules, and therapy discontinued if enzyme levels persist above 3 times the upper limit of normal.

5.4 Serum Creatinine

Reversible elevations in serum creatinine have been reported in patients receiving fenofibric acid delayed-release capsules as well as patients receiving fenofibrate. In the pooled analysis of three 12-week, double-blind, controlled studies of fenofibric acid delayed-release capsules, increases in creatinine to > 2 mg/dL occurred in 0.8% of patients treated with fenofibric acid delayed-release capsules without other lipid-altering drugs. Elevations in serum creatinine were generally stable over time with no evidence for continued increases in serum creatinine with long-term therapy and tended to return to baseline following discontinuation of treatment. The clinical significance of these observations is unknown. Monitoring renal function in patients with renal impairment taking fenofibric acid delayed-release capsules are suggested. Renal monitoring should be considered for patients at risk for renal insufficiency, such as the elderly and those with diabetes.

5.5 Cholelithiasis

Fenofibric acid delayed-release capsules, like fenofibrate, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Fenofibric acid delayed-release capsules therapy should be discontinued if gallstones are found.

5.6 Coumarin Anticoagulants

Caution should be exercised when fenofibric acid delayed-release capsules is given in conjunction with oral coumarin anticoagulants. Fenofibric acid delayed-release capsules may potentiate the anticoagulant effects of these agents resulting in prolongation of the prothrombin time/International Normalized Ratio (PT/INR). Frequent monitoring of PT/INR and dose adjustment of the oral anticoagulant are recommended until the PT/INR has stabilized in order to prevent bleeding complications


[see Drug Interactions ( 7.1 )]


.

5.7 Pancreatitis

Pancreatitis has been reported in patients taking drugs of the fibrate class, including fenofibric acid delayed-release capsules. 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 Hematological Changes

Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of fenofibric acid delayed-release capsules and fenofibrate therapy. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with fenofibrates. Periodic monitoring of red and white blood cell counts are recommended during the first 12 months of fenofibric acid delayed-release capsules administration.

5.9 Hypersensitivity Reactions

Acute HypersensitivityAnaphylaxis
. If a patient develops signs or symptoms of an acute hypersensitivity reaction, advise them to seek immediate medical attention and discontinue fenofibrate.
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 HypersensitivitySevere
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.
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 PE 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.

6.1 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.Fenofibric acid is the active metabolite of fenofibrate. Adverse events reported by 2% or more of patients treated with fenofibrate and greater than placebo during double-blind, placebo- controlled trials are listed in Table 1. Adverse events led to discontinuation of treatment in 5 % of patients treated with fenofibrate and in 3% treated with placebo. Increases in liver tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.Table 1. Adverse Events Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled TrialsBODY SYSTEMAdverse EventFenofibrate*(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%


INVESTIGATIONS


 


 


Abnormal Liver Tests


7.5%


1.4%


Increased AST


3.4%


0.5%


Increased ALT


3%


1.6%


Increased Creatine Phosphokinase


3%


1.4%


RESPIRATORY


 


 


Respiratory Disorder


6.2%


5.5%


Rhinitis


2.3%


1.1%


* Dosage equivalent to 135 mg fenofibric acid delayed-release capsules.


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.Clinical trials with fenofibric acid delayed-release capsules did not include a placebo-control arm. However, the adverse event profile of fenofibric acid delayed-release capsules was generally consistent with that of fenofibrate. The following adverse events not listed above were reported in ≥ 3% of patients taking fenofibric acid delayed-release capsules alone:Gastrointestinal Disorders: Diarrhea, dyspepsia


General Disorders and Administration Site Conditions: Pain


Infections and Infestations: Nasopharyngitis, sinusitis, upper respiratory tract infection


Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia, pain in extremity


Nervous System Disorders: Dizziness

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: rhabdomyolysis, pancreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, anemia, asthenia,  severely depressed HDL-cholesterol levels, and interstitial lung disease.Photosensitivity reactions to fenofibrate have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.

7.1 Coumarin Anticoagulants

Potentiation of coumarin-type anticoagulant effect has been observed with prolongation of the PT/INR.Caution should be exercised when oral coumarin anticoagulants are given in conjunction with fenofibric acid delayed-release capsules. The dosage of the anticoagulant 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 Bile Acid Binding Resins

Since bile acid binding resins may  bind other drugs given concurrently, patients should take  fenofibric acid delayed-release capsules  at least 1 hour before or 4 to 6 hours  after  a bile acid resin to avoid impeding  its  absorption.

7.3 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 drugs of the fibrate class including fenofibric acid delayed-release capsules, there is a risk that an interaction will lead to deterioration of renal function. The benefits and risks of using fenofibric acid delayed-release capsules with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed

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.

8.1 Pregnancy

Risk SummaryLimited
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 135 mg daily, based on body surface area (mg/m


2). Adverse reproductive outcomes occurred at higher doses in the presence of maternal toxicity (see Data). Fenofibric acid delayed-release capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


The
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 to 4% and 15 to 20%, respectively.DataAnimal Data In pregnant rats
In pregnant rats
given oral dietary doses of 14, 127, and 361 mg/kg/day from gestation day 6 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 135 mg fenofibric acid delayed-release capsules 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 
In 
pregnant rabbits given oral gavage doses of 15, 150, and 300 mg/kg/day from gestation day 6 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
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.

8.2 Lactation

Risk SummaryThere
.
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 fenofibric acid delayed-release capsules and for 5 days after the final dose


[see


Contraindications (4)]


.

8.4 Pediatric Use

The safety and effectiveness of fenofibric acid delayed-release capsules in pediatric patients have not been established.

8.5 Geriatric Use

Fenofibric acid delayed-release capsules is substantially excreted by the kidney as fenofibric acid and fenofibric acid glucuronide, 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 fenofibric acid delayed-release capsules.

8.6 Renal Impairment

The use of fenofibric acid delayed-release capsules 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 fenofibric acid delayed-release capsules 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 fenofibric acid delayed-release capsules. 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 a fenofibric acid delayed-release capsule is highly bound to plasma proteins, hemodialysis should not be considered.

11 Description

Fenofibric acid delayed-release capsules (fenofibric acid) are a lipid regulating agent available as delayed release capsules for oral administration. Each delayed release capsule contains choline fenofibrate, equivalent to 45 mg or 135 mg of fenofibric acid. The chemical name for choline fenofibrate is ethanaminium, 2-­hydroxy-N,N,N-trimethyl, 2-{4-(4-chlorobenzoyl)phenoxy] -2-methylpropanoate (1:1) with the following structural formula:


The empirical formula is C


22H


28ClNO


5 and the molecular weight is 421.91. Choline fenofibrate is freely soluble in methanol, sparingly soluble in ethanol and water, slightly soluble in DMSO and practically insoluble in dichloromethane. The melting point is approximately 210°C. Choline fenofibrate is a white to off white crystalline powder, which is stable under ordinary conditions.


Each delayed release capsule contains enteric coated mini-tablets comprised of choline fenofibrate and the following inactive ingredients: hypromellose, hydroxypropyl cellulose, methacrylic acid - ethyl acrylate copolymer (1:1) type A , microcrystalline cellulose, povidone K30, silicon dioxide, sodium stearyl fumarate, talc, triethyl citrate. The capsule shell of the 45 mg capsule contains the following inactive ingredients: ferrosoferric oxide, ferric oxide red, gelatin and titanium dioxide. The capsule shell of the 135 mg capsule contains the following inactive ingredients: FD&C blue no.1, FD&C red no.3, FD&C red no. 40, gelatin and titanium dioxide.

12.1 Mechanism Of Action

The active moiety of fenofibric acid delayed-release capsules 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, fenofibric acid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CIII (an inhibitor of lipoprotein lipase activity).


Activation of PPARα also induces an increase in the synthesis of HDL-C and Apo AI and AII.

12.3 Pharmacokinetics

Fenofibric acid delayed-release capsules contain fenofibric acid, which is the only circulating pharmacologically active moiety in plasma after oral administration of fenofibric acid delayed-release capsules. Fenofibric acid is also the circulating pharmacologically active moiety in plasma after oral administration of fenofibrate, the ester of fenofibric acid.Plasma concentrations of fenofibric acid after administration of one 135 mg fenofibric acid delayed-release capsules delayed release capsule are equivalent to those after one 200 mg capsule of micronized fenofibrate administered under fed conditions.AbsorptionFenofibric acid is well absorbed throughout the gastrointestinal tract. The absolute bioavailability of fenofibric acid is approximately 81%.Peak plasma levels of fenofibric acid occur within 4 to 5 hours after a single dose administration of fenofibric acid delayed-release capsules under fasting conditions.Fenofibric acid exposure in plasma, as measured by C


max and AUC, is not significantly different when a single 135 mg dose of fenofibric acid delayed-release capsules is administered under fasting or nonfasting conditions.


DistributionUpon multiple dosing of fenofibric acid delayed-release capsules, fenofibric acid levels reach steady state within 8 days. Plasma concentrations of fenofibric acid at steady state are approximately slightly more than double those following a single dose. Serum protein binding is approximately 99% in normal and dyslipidemic subjects.MetabolismFenofibric 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 after fenofibrate administration indicate that fenofibric acid does not undergo oxidative metabolism (e.g., cytochrome P450) to a significant extent.


EliminationAfter absorption, fenofibric acid delayed-release capsules are primarily excreted in the urine in the form of fenofibric acid and fenofibric acid glucuronide.Fenofibric acid is eliminated with a half-life of approximately 20 hours, allowing once daily administration of fenofibric acid delayed-release capsules.Specific PopulationsGeriatricsIn five elderly volunteers 77 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 an equivalent dose of fenofibric acid delayed-release capsules can be used in elderly subjects with normal renal function, without increasing accumulation of the drug or metabolites


[see


Use in Specific Populations (8.5)]


.


PediatricsThe pharmacokinetics of fenofibric acid delayed-release capsules has not been studied in pediatric populations.GenderNo pharmacokinetic difference between males and females has been observed for fenofibric acid delayed-release capsules.RaceThe influence of race on the pharmacokinetics of fenofibric acid delayed-release capsules has not been studied; however, fenofibric acid is not metabolized by enzymes known for exhibiting inter-ethnic variability.Renal ImpairmentThe 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


2) 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. Patients with mild to moderate renal impairment (eGFR 30 to 59 mL/min/1.73m


2) 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 fenofibric acid delayed-release capsules 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 ImpairmentNo pharmacokinetic studies have been conducted in patients with hepatic impairment.Drug-drug InteractionsIn vitro studies using human liver microsomes indicate that fenofibric acid is not an inhibitor of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. It is a weak inhibitor of CYP2C8, CYP2C19, and CYP2A6, and mild-to-moderate inhibitor of CYP2C9 at therapeutic concentrations.


Comparison of atorvastatin exposures when atorvastatin (80 mg once daily for 10 days) is given in combination with fenofibric acid (Fenofibric acid delayed-release capsules 135 mg once daily for 10 days) and ezetimibe (10 mg once daily for 10 days) versus when atorvastatin is given in combination with ezetimibe only (ezetimibe 10 mg once daily and atorvastatin, 80 mg once daily for 10 days): The Cmax decreased by 1% for atorvastatin and ortho-hydroxy-atorvastatin and increased by 2% for parahydroxy­atorvastatin. The AUC decreased 6% and 9% for atorvastatin and orthohydroxy-atorvastatin, respectively, and did not change for para-hydroxy-atorvastatin.Comparison of ezetimibe exposures when ezetimibe (10 mg once daily for 10 days) is given in combination with fenofibric acid (Fenofibric acid delayed-release capsules135 mg once daily for 10 days) and atorvastatin (80 mg once daily for 10 days) versus when ezetimibe is given in combination with atorvastatin only (ezetimibe 10 mg once daily and atorvastatin, 80 mg once daily for 10 days): The Cmax increased by 26% and 7% for total and free ezetimibe, respectively. The AUC increased by 27% and 12% for total and free ezetimibe, respectively.Table 2 describes the effects of co-administered drugs on fenofibric acid systemic exposure. Table 3 describes the effects of co-administered fenofibric acid on other drugs.Table 2. Effects of Co-Administered Drugs on Fenofibric Acid Systemic Exposure from Fenofibric Acid Delayed-Release Capsules or Fenofibrate AdministrationCo-AdministeredDrugDosage Regimen  of Co-Administered DrugDosage Regimen of fenofibric acid delayed-release capsulesor FenofibrateChanges in Fenofibric Acid ExposureAUCCmaxLipid-lowering agentsRosuvastatin


40 mg once daily for 10 days


Fenofibric acid delayed-release capsules135 mg once daily for 10 days


↓2%


↓2%


Atorvastatin


20 mg once daily for 10 days


Fenofibrate 160 mg


1 once daily for 10 days


↓2%


↓4%


Atorvastatin +


Atorvastatin, 80 mg once daily


Fenofibric acid delayed-release capsules135 mg once


↑5%


↑5%


ezetimibe


and ezetimibe, 10 mg once daily for 10 days


daily for 10 days


Pravastatin


40 mg as a single dose


Fenofibrate 3 x 67 mg


2 as a single dose


↓1%


↓2%


Fluvastatin


40 mg as a single dose


Fenofibrate 160 mg


1 as a single dose


↓2%


↓10%


Simvastatin


80 mg once daily for 7 days


Fenofibrate 160 mg


1 once daily for 7 days


↓5%


↓11%


Anti-diabetic agentsGlimepiride


1 mg as a single dose


Fenofibrate 145 mg


1once daily for 10 days


↑1%


↓1%


Metformin


850 mg 3 times daily for 10 days


Fenofibrate 54 mg


13 times daily for 10 days


↓9%


↓6%


Rosiglitazone


8 mg once daily for 5 days


Fenofibrate 145 mg


1 once daily for 14 days


↑10%


↑3%


Gastrointestinal agentsOmeprazole


40 mg once daily for 5 days


Fenofibric acid delayed-release capsules135 mg as a single dose fasting


↑6%


↑17%


Omeprazole


40 mg once daily for 5 days


Fenofibric acid delayed-release capsules135 mg as a single dose with food


↑4%


↓2%


1TriCor (fenofibrate) oral tablet


2 TriCor (fenofibrate) oral micronized capsule


Table 3. Effects of Fenofibric Acid Delayed-Release Capsules or Fenofibrate Co-Administration on Systemic Exposure of Other DrugsDosage Regimen of Fenofibric acid delayed-release capsules or FenofibrateDosage Regimen ofCo-Administered DrugChange in Co-Administered Drug ExposureAnalyte


AUC


Cmax


Lipid-lowering agentsFenofibric acid delayed-release capsules135 mg once daily for 10 days


Rosuvastatin, 40 mg once daily for 10 days


Rosuvastatin


↑6%


↑20%


Fenofibrate 160 mg


1 once daily for 10 days


Atorvastatin, 20 mg once daily for 10 days


Atorvastatin


↓17%


0%


Fenofibrate 3 x 67 mg


2 as a single dose


Pravastatin, 40 mg as a single dose


Pravastatin


↑13%


↑13%


 


 


3α-Hydroxyl-iso­ pravastatin


↑26%


↑29%


Fenofibrate 160 mg


1 as a single dose


Fluvastatin, 40 mg as a single dose


(+)-3R, 5S­


Fluvastatin


↑15%


↑16%


Fenofibrate 160 mg


1 once daily for 7 days


Simvastatin, 80 mg once daily for 7 days


Simvastatin acid


↓36%


↓11%


Simvastatin


↓11%


↓17%


Active HMG-CoA Inhibitors


↓12%


↓1%


Total HMG-CoA Inhibitors


↓8%


↓10%


Anti-diabetic agentsFenofibrate 145 mg


1 once


daily for 10 days


Glimepiride, 1 mg as a single dose


Glimepiride


↑35%


↑18%


Fenofibrate 54 mg


1 3 times daily for 10 days


Metformin, 850 mg 3 times daily for 10 days


Metformin


↑3%


↑6%


Fenofibrate 145 mg


1 once daily for 14 days


Rosiglitazone, 8 mg once daily for 5 days


Rosiglitazone


↑6%


↓1%


1 TriCor (fenofibrate) oral tablet


2TriCor (fenofibrate) oral micronized capsule

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

Fenofibric acid delayed-release capsules (fenofibric acid)No carcinogenicity and fertility studies have been conducted with choline fenofibrate or fenofibric acid. However, because fenofibrate is rapidly converted to its active metabolite, fenofibric acid, either during or immediately following absorption both in animals and humans, studies conducted with fenofibrate are relevant for the assessment of the toxicity profile of fenofibric acid. A similar toxicity spectrum is expected after treatment with either fenofibric acid delayed-release capsules or fenofibrate.FenofibrateTwo dietary carcinogenicity studies have been conducted in rats with fenofibrate. In the first 24­ month study, Wistar rats were dosed with fenofibrate at 10, 45, 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 135 mg fenofibric acid delayed-release capsules 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 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 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


2 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, 45, 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, 60, 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).

14.1 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 135 mg once daily of fenofibric acid delayed-release capsules decreased primarily VLDL-TG and VLDL-C. Treatment of patients with elevated TG often results in an increase of LDL-C (Table 4).Table 4. Effects of Fenofibrate in Patients With Severe HypertriglyceridemiaStudy 1PlaceboFenofibrateBaseline TG levels 350 to 499 mg/dLNBaseline Mean (mg/dL)Endpoint Mean (mg/dL)Mean % ChangeNBaseline Mean (mg/dL)Endpoint Mean (mg/dL)Mean % ChangeTriglyceride  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 2PlaceboFenofibrateBaseline TG levels 500 to 1500 mg/dLNBaseline Mean (mg/dL)Endpoint Mean (mg/dL)Mean % ChangeNBaseline Mean (mg/dL)Endpoint Mean (mg/dL)Mean % ChangeTriglycerides


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


48


30


36


22.9*


LDL Cholesterol


42


100


90


-4.2


45


103


131


45*


VLDL Cholesterol


42


137


142


11


45


126


54


-49.4*


* = p < 0.05 vs. Placebo

14.2 Primary Hypercholesterolemia (Heterozygous Familial And Nonfamilial) And Mixed

The effects of fenofibrate at a dose equivalent to fenofibric acid delayed-release capsules135 mg once daily 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 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 (Table 5).Table 5. Mean Percent Change in Lipid Parameters at End of Treatment†Treatment GroupTotal-C (mg/dL)LDL-C (mg/dL)HDL-C(mg/dL)TG (mg/dL)Pooled Cohort 


 


 


 


Mean baseline lipid values (n = 646)


306.9


213.8


52.3


191


All Fenofibrate (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 andTG < 150 mg/dL 


 


 


 


Mean baseline lipid values (n = 334)


307.7


227.7


58.1


101.7


All Fenofibrate (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 andTG ≥ 150 mg/dL 


 


 


 


Mean baseline lipid values (n =242)


312.8


219.8


46.7


231.9


All Fenofibrate (n = 126)


-16.8%*


-20.1%*


+14.6%*


-35.9%*


Placebo (n = 116)


-3%


-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).

16 How Supplied/Storage And Handling

Fenofibric Acid Delayed-Release Capsules 45 mg:Reddish brown opaque cap imprinted with “CDR”, yellow opaque body imprinted with “45”, size “3”, hard gelatin capsule contains 4 white to off-white, round, biconvex delayed release mini tablets.


Bottles of 30                                                               NDC 42571-347-30Bottles of 90                                                               NDC 42571-347-90Fenofibric Acid Delayed-Release Capsules 135 mg:Blue opaque cap imprinted with “CDR” and yellow opaque body imprinted with “135 mg”, size “0”, hard gelatin capsule contains 12 white to off-white, round, biconvex delayed release mini tablets.


Bottles of 30                                                               NDC 42571-348-30Bottles of 90                                                               NDC 42571-348-90Bottles of 500                                                             NDC 42571-348-05Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP controlled room temperature]. Keep out of the reach of children. Protect from moisture.

17 Patient Counseling Information

  • Patients should be advised:of the potential benefits and risks of fenofibric acid delayed-release capsules.not to use fenofibric acid delayed-release capsules if there is a known hypersensitivity to fenofibrate or fenofibric acid.of medications that should not be taken in combination with fenofibric acid delayed-release capsules.that if they are taking coumarin anticoagulants, fenofibric acid delayed-release capsules may increase their anti-coagulant effect, and increased monitoring may be necessary.to continue to follow an appropriate lipid-modifying diet while taking fenofibric acid delayed-release capsules.to take fenofibric acid delayed-release capsules once daily, without regard to food, at the prescribed dose, swallowing each capsule 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 fenofibric acid delayed-release capsules.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 fenofibric acid delayed-release capsules and for 5 days after the final dose.Manufactured by:Micro Labs LimitedGoa-403 722, INDIA.M. L. No.: 651Manufactured for:Micro Labs USA Inc.Basking Ridge, NJ 07920Revised: April 2020

* Please review the disclaimer below.