Fenofibric Acid

The molecular formula is C₂₂H₂₈ClNO₅ and the molecular weight is 421.91. Choline fenofibrate is freely soluble in water. The melting point is approximately 210°C. Choline fenofibrate is a white to almost white crystalline powder, which is stable under ordinary conditions.

Each delayed-release capsule contains enteric coated pellets comprised of choline fenofibrate and the following inactive ingredients: colloidal silicon dioxide, gelatin, hydroxypropyl cellulose, hypromellose, methacrylic acid copolymer type C, polysorbate 80, povidone, sodium lauryl sulfate, sodium stearyl fumarate, talc, titanium dioxide, triethyl citrate and yellow iron oxide. The 45 mg capsules also contain red iron oxide. The 135 mg capsules also contain FD&C Blue No. 2. The black imprinting ink contains ammonium hydroxide, black iron oxide, propylene glycol and shellac glaze.

12 CLINICAL PHARMACOLOGY

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).

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 HDL-C and Apo AI and AII.

12.2 Pharmacodynamics

Elevated levels of Total-C, LDL-C and Apo B, and decreased levels of HDL-C and its transport complex, Apo AI and Apo AII, are risk factors for human atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the levels 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, TG, and triglyceride-rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibric acid results in increases in HDL-C and Apo AI and Apo 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. 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 capsule are equivalent to those after one 200 mg capsule of micronized fenofibrate administered under fed conditions.

Absorption

Fenofibric 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 capsule 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 is administered under fasting or nonfasting conditions.

Distribution

Upon multiple dosing of fenofibric acid, 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.

Metabolism

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 after fenofibrate administration indicate that fenofibric acid does not undergo oxidative metabolism (e.g., cytochrome P450) to a significant extent.

Excretion

After absorption, fenofibric acid is 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.

Specific Populations

Geriatrics

In 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 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) ].

Pediatrics

The pharmacokinetics of fenofibric acid has not been studied in pediatric populations.

Gender

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

Race

The influence of race on the pharmacokinetics of fenofibric acid has not been studied; however, fenofibric acid 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/1.73 m²) 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/1.73 m²) 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 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 (2.5)].

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 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 C_max decreased by 1% for atorvastatin and ortho-hydroxy-atorvastatin and increased by 2% for parahydroxy-atorvastatin. 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 capsules 135 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 C_max 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 3 describes the effects of coadministered drugs on fenofibric acid systemic exposure.
Table 4 describes the effects of coadministered fenofibric acid on other drugs.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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 or fenofibrate.

Fenofibrate

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, 45 and 200 mg/kg/day, approximately 0.3, 1 and 6 times the maximum recommended human dose (MRHD), based on body surface area comparisons (mg/m²). At a dose of 200 mg/kg/day (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 interstitial cell tumors of the testes 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), clofibrate (400 mg/kg/day; 2 times the human dose) and gemfibrozil (250 mg/kg/day; 2 times the MRHD). 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 on the basis of mg/m² surface area) 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 and 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.

Mutagenesis

Fenofibrate has been demonstrated to be devoid of mutagenic potential in the following tests: Ames, and micronucleus in vivo/rat. In addition, fenofibric acid, has been demonstrated to be devoid of mutagenic potential in the following tests: Ames, mouse lymphoma, chromosomal aberration and sister chromatid exchange in human lymphocytes, and unscheduled DNA synthesis in primary rat hepatocytes.

Impairment of Fertility

In a fertility study, rats were given oral dietary doses of fenofibrate. Males received doses for 61 days prior to mating and females for 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 mg/m² surface area comparisons).

14 CLINICAL STUDIES

14.1 Coadministration Therapy with Statins

Efficacy and safety of fenofibric acid coadministered with statins were assessed in three 12-week, double-blind, controlled Phase 3 studies and one 52-week, long-term, open-label extension study in 2,698 patients with mixed dyslipidemia. Patients were required to meet the following fasting lipid entry criteria: TG ≥ 150 mg/dL, and HDL-C < 40 mg/dL (males) and < 50 mg/dL (females), and LDL-C ≥ 130 mg/dL. The three multicenter, randomized, double-blind, controlled studies had similar designs, differing primarily in the statin used for combination therapy/monotherapy. Each study compared the effects of 135 mg fenofibric acid coadministered with either a low dose or a moderate dose of statin with fenofibric acid monotherapy and statin monotherapy at the corresponding dose on CHD lipid risk factors. A smaller group of patients received a high dose of statin monotherapy. In study 1, patients received fenofibric acid coadministered with 10 mg or 20 mg rosuvastatin. In study 2, patients received fenofibric acid coadministered with 20 mg or 40 mg simvastatin. In study 3, patients received fenofibric acid coadministered with 20 mg or 40 mg atorvastatin.

Patients were enrolled for a total of approximately 22 weeks, consisting of a 6-week diet run-in/washout period, a 12-week treatment period and a 30-day safety follow up period. Patients who completed the 12-week treatment period were eligible to participate in the 52-week long-term extension study. Of the 2,698 randomized and treated subjects in the controlled studies, 51.6% were female and 48.4% were male; 92.6% of all subjects were White, 4.7% were Black and 2.8% were of other races. Hispanics comprised 9.9% of the study population. Mean age was 54.9 years.

The primary efficacy endpoints for all three studies were mean percent changes from baseline to final value in HDL-C, TG and LDL-C. For each statin dose coadministered with fenofibric acid, there were three primary comparisons. For HDL-C and TG, fenofibric acid coadministered with each statin dose was compared with statin monotherapy at the corresponding dose. For LDL-C, fenofibric acid coadministered with each statin dose was compared with fenofibric acid monotherapy. In order to declare combination therapy successful for a particular statin dose, all three primary comparisons were required to demonstrate superiority of the combination therapy over the corresponding monotherapy. The primary efficacy results were consistent in the three studies and were confirmed by the pooled analysis of the three studies. The results from the individual studies and the pooled analysis demonstrated that fenofibric acid coadministered with low-dose statins and moderate-dose statins was superior to the corresponding monotherapy. Statistically significant differences were observed for all three primary efficacy comparisons for both doses of combination therapy in all three double-blind, controlled studies as well as the pooled analysis.

In the pooled analysis, fenofibric acid coadministered with both low-dose statins and moderate-dose statins resulted in mean percent increases (18.1% and 17.5%) in HDL-C and mean percent decreases (-43.9% and -42%) in TG that were significantly greater than the corresponding dose of statin monotherapy (7.4% and 8.7% for HDL-C; -16.8% and -23.7% for TG). In addition, both doses of combination therapy resulted in mean percent decreases (-33.1% and -34.6%) in LDL-C that were significantly greater than fenofibric acid monotherapy (-5.1%). The results of the pooled analysis are described in Table 5.

Secondary efficacy endpoints in all three double-blind, controlled studies were percent changes in non-HDL-C (fenofibric acid coadministered with statin compared to fenofibric acid monotherapy and corresponding statin monotherapy), and percent changes in VLDL-C, Total-C and Apo B (fenofibric acid coadministered with statin compared to corresponding statin monotherapy). Coadministration of fenofibric acid with statins resulted in the following changes in secondary parameters (Table 6).

A total of 1,895 patients who completed 12 weeks of treatment in the double-blind, controlled studies were treated in the 52-week, long-term extension study. Patients received fenofibric acid coadministered with the moderate-dose of the statin that had been used in the double-blind, controlled study in which they were enrolled. Whether combination therapy was initiated during the double-blind, controlled studies or introduced during the long-term extension study, the treatment effect of combination therapy was observed within 4 weeks, and was sustained over the duration of treatment in the long-term study. A total of 568 patients completed 52 weeks of treatment with fenofibric acid coadministered with statins. Mean 52-week values and mean percent change from baseline (at time of enrollment in randomized controlled trials) were 91.7 mg/dL (-38.2%) for LDL-C, 47.3 mg/dL (+ 24%) for HDL-C, 135.5 mg/dL (-47.6%) for TG, 117.9 mg/dL (-45.7%) for non-HDL-C, 26.2 mg/dL (-53.1%) for VLDL-C, 165.2 mg/dL (-35.4%) for Total-C, and 81.4 mg/dL (-43.6%) for Apo B.

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 8 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 decreased primarily VLDL-TG and VLDL-C. Treatment of patients with elevated TG often results in an increase of LDL-C (Table 7).

14.3 Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia

The effects of fenofibrate at a dose equivalent to fenofibric acid 135 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 8).

Table 8. Mean Percent Change in Lipid Parameters at End of TreatmentDuration of study treatment was 3 to 6 months

Treatment Group	Total-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%p = < 0.05 vs. Placebo	-20.6%p = < 0.05 vs. Placebo	+11%p = < 0.05 vs. Placebo	-28.9%p = < 0.05 vs. Placebo
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	227.7	58.1	101.7
All Fenofibrate (n = 193)	-22.4%p = < 0.05 vs. Placebo	-31.4%p = < 0.05 vs. Placebo	+9.8%p = < 0.05 vs. Placebo	-23.5%p = < 0.05 vs. Placebo
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	219.8	46.7	231.9
All Fenofibrate (n = 126)	-16.8%p = < 0.05 vs. Placebo	-20.1%p = < 0.05 vs. Placebo	+14.6%p = < 0.05 vs. Placebo	-35.9%p = < 0.05 vs. Placebo
Placebo (n = 116)	-3%	-6.6%	+2.3%	+0.9%

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 contains choline fenofibrate equivalent to 45 mg or 135 mg of fenofibric acid.

The 45 mg capsules are hard-shell gelatin capsules with a brown-pink opaque cap and light yellow opaque body, fill with white to off-white enteric coated pellets. The capsule is axially printed with MYLAN over CF 45 in black ink on the cap and body.

NDC 0378-2589-93
bottles of 30 capsules

NDC 0378-2589-77
bottles of 90 capsules

NDC 0378-2589-05
bottles of 500 capsules

The 135 mg capsules are hard-shell gelatin capsules with a powder blue opaque cap and light yellow opaque body filled with white to off-white enteric coated pellets. The capsule is axially printed with MYLAN over CF 135 in black ink on the cap and body.

NDC 0378-2590-93
bottles of 30 capsules

NDC 0378-2590-77
bottles of 90 capsules

NDC 0378-2590-05
bottles of 500 capsules

Storage and Handling: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Protect from moisture.

PHARMACIST: Dispense a Medication Guide with each prescription.

17 PATIENT COUNSELING INFORMATION

See Medication Guide

17.1 Patient Counseling

Patients should be advised:

• •of the potential benefits and risks of fenofibric acid delayed-release capsules.
• •to read the Medication Guide before starting fenofibric acid delayed-release capsules therapy and to reread it each time the prescription is renewed.
• •of medications that should not be taken in combination with fenofibric acid delayed-release capsules.
• •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. If fenofibric acid delayed-release capsules are coadministered with a statin, they may be taken together.
• •to return 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.

Medication Guide

Fenofibric Acid Delayed-release Capsules
(fen″ oh fye′ brik as′ id)
45 mg and 135 mg

Read this Medication Guide before you start taking fenofibric acid delayed-release capsules and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about fenofibric acid delayed-release capsules?

Fenofibric acid delayed-release capsules can be used with other cholesterol-lowering medicines called statins. Statins include:

• •atorvastatin (Lipitor^*, Caduet^*)
• •fluvastatin (Lescol^*, Lescol XL^*) ,
• •lovastatin (Altoprev^*, Mevacor^*, Advicor^*)
• •pitavastatin (Livalo^*)
• •pravastatin (Pravachol^*)
• •rosuvastatin (Crestor^*)
• •simvastatin (Zocor^*, Simcor^*, Vytorin^*)

Statins can cause muscle pain, tenderness or weakness, which may be symptoms of a rare but serious muscle condition called rhabdomyolysis. In some cases rhabdomyolysis can cause kidney damage and death. The risk of rhabdomyolysis may be higher when fenofibric acid delayed-release capsules are given with statins. If you take a statin, tell your healthcare provider.

Other medicines or large amounts of grapefruit juice (more than a quart) may raise the levels of statins in your body, and could then raise the risk of muscle problems. Tell your healthcare provider if you are taking any medicines listed below.

• •Heart medicine
• •Stomach medicine
• •Antibiotic
• •Anti-fungal
• •Cholesterol-lowering medicine
• •Hormones
• •HIV/AIDS medicine
• •Antidepressant
• •Immunosuppressant
• •Anti-seizure medicine

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Tell your healthcare provider if you drink grapefruit juice.

What are fenofibric acid delayed-release capsules?

Fenofibric acid delayed-release capsules are a prescription medicine used to treat cholesterol in the blood by lowering the total amount of triglycerides and LDL (bad) cholesterol and increasing the HDL (good) cholesterol. Fenofibric acid delayed-release capsules have not been shown to lower your risk of having heart problems or a stroke. You should be on a low fat and low cholesterol diet while you take fenofibric acid delayed-release capsules.

The safety and effectiveness of fenofibric acid delayed-release capsules in children is not known.

Who should not take fenofibric acid delayed-release capsules?

Do not take fenofibric acid delayed-release capsules if you:

• •are allergic to fenofibric acid, or any of the ingredients in fenofibric acid delayed-release capsules. See the end of this Medication Guide for a list of all the ingredients in fenofibric acid delayed-release capsules.
• •have severe kidney disease
• •have liver disease
• •have gallbladder disease
• •are a nursing mother

Talk to your healthcare provider before you take fenofibric acid delayed-release capsules if you have any of these conditions.

What should I tell my healthcare provider before taking fenofibric acid delayed-release capsules?

Before taking fenofibric acid delayed-release capsules, tell your healthcare provider about all your medical conditions, including if you:

• •are allergic to any medicines.
• •have ever had kidney problems.
• •have ever had liver problems.
• •have ever had gallbladder problems.
• •are pregnant or if you plan to become pregnant. It is not known if fenofibric acid delayed-release capsules will harm your unborn baby.
• •are breast-feeding or plan to breastfeed. It is not known if fenofibric acid delayed-release capsules passes into your breast milk. You and your healthcare provider should decide if you will take fenofibric acid delayed-release capsules or breast-feed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Using fenofibric acid delayed-release capsules with certain other medicines can affect the way these medicines work and other medicines may affect how fenofibric acid delayed-release capsules works. In some cases, using fenofibric acid delayed-release capsules with other medicines can cause serious side effects.

Know all the medicines you take. Keep a list of them and show it to your healthcare provider when you get a new medicine.

It is especially important to tell your healthcare provider if you take any of the medicines mentioned in, “What is the most important information I should know about fenofibric acid delayed-release capsules?” or any of the medicines listed below:

• • anticoagulants, also known as blood thinners (warfarin, Coumadin*)
• • bile acid resins
• • cyclosporine

Ask your healthcare provider if you are not sure if your medicine is one of these.

How should I take fenofibric acid delayed-release capsules?

• •You should be on a low fat and low cholesterol diet while you take fenofibric acid delayed-release capsules.
• •Take fenofibric acid delayed-release capsules one time each day as prescribed by your healthcare provider.
• •Take fenofibric acid delayed-release capsules with or without food.
• •Swallow fenofibric acid delayed-release capsules whole. Do not break, crush, dissolve or chew fenofibric acid delayed-release capsules before swallowing. If you cannot swallow fenofibric acid delayed-release capsules whole, tell your healthcare provider, you may need a different medicine.
• •If you take a medicine called a statin, you can take fenofibric acid delayed-release capsules and your statin at the same time of day.
• •If you miss a dose of fenofibric acid delayed-release capsules, 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 fenofibric acid delayed-release capsules a day unless your healthcare provider tells you to.
• •If you take too much fenofibric acid delayed-release capsules, contact your healthcare provider or your local emergency department.
• •Do not change your dose or stop fenofibric acid delayed-release capsules unless your healthcare provider tells you to.
• •Your healthcare provider may do blood tests before you start taking fenofibric acid delayed-release capsules and during treatment. See your healthcare provider regularly to check your cholesterol and triglyceride levels and to check for side effects.

What are the possible side effects with fenofibric acid delayed-release capsules?

Fenofibric acid delayed-release capsules may cause serious side effects, including:

• • muscle pain, tenderness, or weakness. See “What is the most important information that I should know about fenofibric acid delayed-release capsules?”
• • tiredness and fever
• • abdominal pain, nausea, or vomiting. These may be signs of inflammation (swelling) of the gallbladder or pancreas.

Call your healthcare provider right away if you have any of these serious side effects.

The most common side effects with fenofibric acid delayed-release capsules include:

• •headache
• •heartburn (indigestion)
• •nausea
• •muscle aches
• •increases in muscle or liver enzymes that are measured by blood tests

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of fenofibric acid delayed-release capsules. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store fenofibric acid delayed-release capsules?

• •Store fenofibric acid delayed-release capsules at 20° to 25°C (68° to 77°F).
• •Protect fenofibric acid delayed-release capsules from moisture.

Keep fenofibric acid delayed-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of fenofibric acid delayed-release capsules

Medicines are sometimes prescribed for conditions that are not mentioned in the Medication Guide. Do not use fenofibric acid delayed-release capsules for a condition for which it was not prescribed. Do not give fenofibric acid delayed-release capsules to other people, even if they have the same condition you have. It may harm them.

This Medication Guide summarizes the most important information about fenofibric acid delayed-release capsules. If you would like more information, talk to your healthcare provider. You can also ask your pharmacist or healthcare provider for information that is written for health professionals.

For more information call Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX).

What are the ingredients in fenofibric acid delayed-release capsules?

Active Ingredient: fenofibric acid

Inactive Ingredients: colloidal silicon dioxide, gelatin, hydroxypropyl cellulose, hypromellose, methacrylic acid copolymer type C, polysorbate 80, povidone, sodium lauryl sulfate, sodium stearyl fumarate, talc, titanium dioxide, triethyl citrate and yellow iron oxide. The 45 mg capsules also contain red iron oxide. The 135 mg capsules also contain FD&C Blue No. 2. The black imprinting ink contains ammonium hydroxide, black iron oxide, propylene glycol and shellac glaze.

^* Brand names mentioned above are the property of their respective owners.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

FEBRUARY 2013
FENC:R1mmt

PRINCIPAL DISPLAY PANEL – 45 mg

NDC 0378-2589-93

Fenofibric Acid
Delayed-release
Capsules
45 mg*

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx only     30 Capsules

*Each capsule contains choline
fenofibrate equivalent to 45 mg
of fenofibric acid.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from moisture.

Usual Dosage: See accompanying
prescribing information.

Swallow whole. Do not open,
crush, dissolve or chew capsules.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Mylan.com

RM2589H

PRINCIPAL DISPLAY PANEL – 135 mg

NDC 0378-2590-93

Fenofibric Acid
Delayed-release
Capsules
135 mg*

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx only     30 Capsules

*Each capsule contains choline
fenofibrate equivalent to 135 mg
of fenofibric acid.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from moisture.

Usual Dosage: See accompanying
prescribing information.

Swallow whole. Do not open,
crush, dissolve or chew capsules.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Mylan.com

RM2590H