Fenoglide

Patients should be advised:

• of the potential benefits and risks of FENOGLIDE
• not to use FENOGLIDE if there is a known hypersensitivity to fenofibrate or fenofibric acid.
• that if they are taking coumarin anticoagulants, FENOGLIDE may increase their anticoagulant effect, and increased monitoring may be necessary.
• of medications that should not be taken in combination with FENOGLIDE.
• to continue to follow an appropriate lipid-modifying diet while taking FENOGLIDE.
• to take FENOGLIDE once daily, without regard to food, at the prescribed dose, swallowing each tablet whole.
• 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 FENOGLIDE.
• to inform their physician of any muscle pain, tenderness, or weakness; onset of abdominal pain; or any other new symptoms.

• You should be on a low fat and low cholesterol diet while you take fenofibrate.
• Take fenofibrate one time each day as prescribed by your healthcare provider.
• Take fenofibrate with or without food.
• Swallow fenofibrate capsules whole. Do not break, crush, dissolve, or chew fenofibrate capsules before swallowing. If you cannot swallow the capsules whole, tell your healthcare provider, you may need a different medicine.
• If you take a medicine called a statin, you can take fenofibrate and your statin at the same time of day.
• If you miss a dose of fenofibrate, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. If you are not sure about your dosing, call your healthcare provider. Do not take more than one dose of fenofibrate a day unless your healthcare provider tells you to.
• If you take too much fenofibrate, contact your healthcare provider or your local emergency department.
• Do not change your dose or stop fenofibrate unless your healthcare provider tells you to.
• Your healthcare provider may do blood tests before you start taking fenofibrate and during treatment. See your healthcare provider regularly to check your cholesterol and triglyceride levels and to check for side effects.

If you take too much fenofibrate call your local Poison Control Center or seek emergency medical treatment right away.

Fenofibrate helps reduce cholesterol and triglycerides (fatty acids) in the blood. High levels of these types of fat in the blood are associated with an increased risk of atherosclerosis (clogged arteries).

Fenofibrate is used to treat high cholesterol and high triglyceride levels.

Fenofibrate may also be used for purposes not listed in this medication guide.

This section provides information on the proper use of a number of products that contain fenofibrate. It may not be specific to Fenoglide. Please read with care.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, or do not use it for a longer time than your doctor ordered.

In addition to this medicine, your doctor may change your diet to one that is low in fat, sugar, and cholesterol. Carefully follow your doctor's order about any special diet.

This medicine is usually taken once a day. Take the medicine at the same time each day to maintain the medication's effect.

Fenoglide®, Lipofen®, Lofibra™, and Tricor® should be taken with a meal. Antara® and Triglide® can be taken with or without a meal.

Swallow Antara® capsules, Tricor® tablets, or Triglide® tablets whole. Do not open, crush, break, chew, or dissolve them. Do not take chipped or broken Triglide® tablets.

If you are also using cholestyramine, colesevelam, or colestipol, you must take Triglide® at least 1 hour before or 4 to 6 hours after you take these medicines.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For high cholesterol:
    • Adults—
      • Antara®: At first, 130 milligrams (mg) once a day with a meal.
      • Lipofen®: At first, 150 mg once a day with a meal. Your doctor may adjust your dose as needed.
      • Lofibra™: 200 mg once a day with a meal.
    • Children—Use and dose must be determined by your doctor.
  • For high triglycerides or fats:
    • Adults—
      • Antara®: At first, 43 to 130 milligrams (mg) once a day with a meal. Your doctor may adjust your dose as needed. However, the dose is usually not more than 130 mg per day.
      • Lipofen®: At first, 50 to 150 mg once a day with a meal. Your doctor may adjust your dose as needed. However, the dose is usually not more than 150 mg per day.
      • Lofibra™: At first, 67 mg once a day with a meal. Your doctor may increase your dose as needed.
    • Children—Use and dose must be determined by your doctor.

• For oral dosage form (tablets):
  • For high cholesterol:
    • Adults—
      • Fenoglide®: At first, 120 milligrams (mg) per day. Your doctor may adjust your dose as needed.
      • Tricor®: At first, 160 mg once a day. Your doctor may adjust your dose as needed.
      • Triglide®: 160 mg once a day.
    • Children—Use and dose must be determined by your doctor.
  • For high triglycerides or fats:
    • Adults—
      • Fenoglide®: At first, 40 to 120 milligrams (mg) per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 120 mg per day.
      • Tricor®: At first, 54 to 160 mg once a day. Your doctor may adjust your dose as needed.
      • Triglide®: 160 mg once a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep Triglide® tablets in its original container. Protect from heat, light, and moisture.

• If you have an allergy to fenofibrate or any other part of Fenoglide (fenofibrate and derivatives tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Gallbladder disease, kidney disease, liver disease, or rise in liver enzymes.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with Fenoglide.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of gallstones like sudden pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; or fever with chills.
• Very bad joint pain or swelling.
• Feeling very tired or weak.
• Chest pain or pressure.
• Fever or chills.
• Shortness of breath.
• Coughing up blood.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Any unexplained bruising or bleeding.
• Very bad muscle problems may happen with Fenoglide. This can also lead to kidney problems. Tell your doctor if you have muscle pain or weakness, mainly if you feel very tired or weak or have a fever. Tell your doctor if you are unable to pass urine or you have a change in how much urine is passed.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Fenoglide (fenofibrate and derivatives tablets), please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Fenoglide. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Fenoglide.

Review Date: October 4, 2017

Mechanism of Action

The active moiety of Fenoglide 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-lowering 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 alpha (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 apoproteins 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.

Pharmacodynamics

A variety of clinical studies have demonstrated that elevated levels of total -C, LDL-C, and apo B, an LDL membrane complex, are risk factors for human atherosclerosis. Similarly, decreased levels of HDL-C and its transport complex, apolipoprotein A (apo AI and apo AII) are risk factors for 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 TG on the risk of cardiovascular morbidity and mortality has not been determined.

Fenofibric acid, the active metabolite of fenofibrate, produces reductions in TC, LDL-C, apo B, total triglycerides, and triglyceride-rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in HDL and apoproteins apo AI and apo AII.

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.

Plasma concentrations of fenofibric acid after single-dose administration of Fenoglide Tablets, 120 mg are equivalent to those of Fenofibrate 130 mg capsules under high-fat conditions.

A high-fat meal did not affect the fenofibric acid AUC after Fenoglide administration but did increase the mean Cmax by 44% compared to fasting conditions.

• 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 from Fenoglide occur, on average, within 2 to 3 hours after administration.
Doses of three Fenoglide (fenofibrate) Tablets, 40 mg are considered to be equivalent to single doses of Fenoglide (fenofibrate) Tablets, 120 mg. • Distribution: In healthy volunteers, steady-state plasma levels of fenofibric acid were shown to be achieved within a week of dosing and did not demonstrate accumulation across time following multiple dose administration. 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 from Fenoglide is eliminated with a half-life of 23 hours, allowing once daily dosing. • Geriatrics: In 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 a similar dosage regimen can be used in the elderly, without increasing accumulation of the drug or metabolites [see Dosage and Administration (2.5) , Use in Specific Populations (8.5)]. • Pediatrics: The pharmacokinetics of Fenoglide 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 were examined in patients with mild, moderate, and severe renal impairment. Patients with severe renal impairment (creatinine clearance [CrCl] ≤30 mL/min or estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m2) 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 (CrCl 30-80 mL/min or eGFR 30-59 mL/min/1.73m2) 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 Fenoglide 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 systemic exposure. Table 2. Effects of Co-Administered Drugs on Fenofibric Acid Systemic Exposure from Fenofibrate Administration

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

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

1 TriCor (fenofibrate) oral tablet
2 TriCor (fenofibrate) oral micronized capsule
Dosage Regimen of Fenofibrate	Dosage Regimen of Co-Administered Drug	Change in Co-Administered Drug Exposure
		Analyte	AUC	Cmax
Lipid-lowering agents
Fenofibrate 160 mg1 once daily for 10 days	Atorvastatin, 20 mg once daily for 10 days	Atorvastatin	↓17%	0%
Fenofibrate 3 x 67 mg2 as a single dose	Pravastatin, 40 mg as a single dose	Pravastatin	↑13%	↑13%
		3α-Hydroxyl-iso-pravastatin	↑26%	↑29%
Fenofibrate 160 mg1 as a single dose	Fluvastatin, 40 mg as a single dose	(+)-3R, 5S-Fluvastatin	↑15%	↑16%
Anti-diabetic agents
Fenofibrate 145 mg1 once daily for 10 days	Glimepiride, 1 mg as a single dose	Glimepiride	↑35%	↑18%
Fenofibrate 54 mg1 three times daily for 10 days	Metformin, 850 mg three times daily for 10 days	Metformin	↑3%	↑6%
Fenofibrate 145 mg1 once daily for 14 days	Rosiglitazone, 8 mg once daily for 5 days	Rosiglitazone	↑6%	↓1%

Patients should be advised:

• of the potential benefits and risks of Fenoglide. • not to use Fenoglide if there is a known hypersensitivity to fenofibrate or fenofibric acid. • that if they are taking coumarin anticoagulants, Fenoglide may increase their anticoagulant effect, and increased monitoring may be necessary. • of medications that should not be taken in combination with Fenoglide. • to continue to follow an appropriate lipid-modifying diet while taking Fenoglide. • to take Fenoglide once daily, without regard to food, at the prescribed dose, swallowing each tablet whole. • 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 Fenoglide. • to inform their physician of any muscle pain, tenderness, or weakness; onset of abdominal pain; or any other new symptoms.

Manufactured for:
Salix Pharmaceuticals, a division of
Valeant Pharmaceuticals North America LLC
Bridgewater, NJ 08807 USA

Fenoglide is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©Valeant Pharmaceuticals North America LLC.

U.S. Patent Numbers: 7,658,944, 8,124,125, 8,481,078, and 9,173,847

Revised: 01/2017

9501801

PCR-750-1004

Bottle LABEL – PRINCIPAL DISPLAY PANEL 40MG

NDC 68012-490-90
Fenoglide®

(fenofibrate) tablets

40 mg

Rx only
90 Tablets
Salix

Bottle LABEL – PRINCIPAL DISPLAY PANEL 120MG

NDC 68012-495-90
Fenoglide®

(fenofibrate)

Tablets

120 mg

Rx only
90 Tablets

Salix

Fenoglide  fenofibrate tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68012-490 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength fenofibrate (FENOFIBRIC ACID) fenofibrate 40 mg

Inactive Ingredients Ingredient Name Strength lactose monohydrate   Polyethylene Glycol 6000   Poloxamer 188   magnesium stearate

Product Characteristics Color white (white) Score no score Shape OVAL (OVAL) Size 13mm Flavor Imprint Code FLO Contains

Packaging # Item Code Package Description 1 NDC:68012-490-90 90 TABLET in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022118 11/18/2010

Fenoglide  fenofibrate tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68012-495 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength fenofibrate (FENOFIBRIC ACID) fenofibrate 120 mg

Inactive Ingredients Ingredient Name Strength lactose monohydrate   Polyethylene Glycol 6000   Poloxamer 188   magnesium stearate

Product Characteristics Color white (white) Score no score Shape OVAL (OVAL) Size 18mm Flavor Imprint Code FHI Contains

Packaging # Item Code Package Description 1 NDC:68012-495-90 90 TABLET in 1 BOTTLE 2 NDC:68012-495-07 6 BOTTLE in 1 BOX 2 7 TABLET in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022118 11/18/2010

Labeler - Santarus, Inc. (104286369)

Establishment
Name	Address	ID/FEI	Operations
Catalent Pharma Solutions		829672745	MANUFACTURE(68012-490, 68012-495)

Establishment
Name	Address	ID/FEI	Operations
Perrigo API Ltd.		600077101	API MANUFACTURE(68012-490, 68012-495)

Establishment
Name	Address	ID/FEI	Operations
Packaging Coordinators Inc		078525133	PACK(68012-490, 68012-495)

Revised: 01/2017   Santarus, Inc.

If you also take cholestyramine, colesevelam, or colestipol: Wait 4 to 6 hours after taking any of these other medicines before you take Fenoglide. Avoid taking this medicine within 1 hour before taking the other medicine.

Avoid drinking alcohol. It can raise triglyceride levels, and may also damage your liver while you are taking Fenoglide.