1 INDICATIONS AND USAGE Fenofibric acid delayed-release capsules are a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as adjunctive therapy to diet to: · Reduce TG in patients with severe hypertriglyceridemia (1.1).

· Reduce elevated LDL-C, Total-C, TG and Apo B, and to increase HDLC in patients with primary hypercholesterolemia or mixed dyslipidemia (1.2).

Limitations of Use: Fenofibrate at a dose equivalent to 135 mg of fenofibric acid delayed-release capsules did not reduce coronary heart disease morbidity and mortality in patients with type 2 diabetes mellitus (5.1) 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 (HDL-C) in patients with primary hypercholesterolemia or mixed dyslipidemia.

1.3 Limitations of Use Fenofibrate at a dose equivalent to 135 mg of fenofibric acid delayed-release capsules did not reduce coronary heart disease morbidity and mortality in 2 large, randomized controlled trials of patients with type 2 diabetes mellitus [see Warnings and Precautions (5.1)] .

1.4 General Considerations for Treatment Laboratory studies should be performed to establish that lipid levels are abnormal before instituting fenofibric acid delayed-release capsules therapy.

Every reasonable attempt should be made to control serum lipids with non-drug methods including appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that may be contributing to the lipid abnormalities.

Medications known to exacerbate hypertriglyceridemia (beta-blockers, thiazides, estrogens) should be discontinued or changed if possible, and excessive alcohol intake should be addressed before triglyceride-lowering drug therapy is considered.

If the decision is made to use lipid-altering drugs, the patient should be instructed that this does not reduce the importance of adhering to diet.

Drug therapy is not indicated for patients who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of VLDL.

6 ADVERSE REACTIONS The most common adverse events reported during clinical trials with fenofibrate (≥ 2% and at least 1% greater than placebo) were abnormal liver tests, increased AST, increased ALT, increased CPK, and rhinitis (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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 Trials BODY SYSTEM Adverse Event Fenofibrate* (N = 439) Placebo (N = 365) BODY AS A WHOLE Abdominal Pain 4.6% 4.4% Back Pain 3.4% 2.5% Headache 3.2% 2.7% DIGESTIVE Nausea 2.3% 1.9% Constipation 2.1% 1.4% 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 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: Dizzinesss 6.2 Postmarketing Experience The following adverse events have been identified during postapproval use of fenofibrate: rhabdomyolysis, pancreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, anemia, asthenia, and severely depressed HDL-cholesterol levels.

Because these events 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.