1 INDICATIONS & USAGE Fenofibrate tablets is a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as an adjunct to diet: • To reduce elevated LDL-C, Total-C, TG and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia ( 1.1 ).

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

Limitations of Use: Fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in patients with type 2 diabetes mellitus ( 5.1 ).

1.1 Primary Hypercholesterolemia or Mixed Dyslipidemia Fenofibrate tablets are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia.

1.2 Severe Hypertriglyceridemia Fenofibrate tablets are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia.

Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacologic intervention.

Markedly elevated levels of serum triglycerides (e.g.

> 2,000 mg/dL) may increase the risk of developing pancreatitis.

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

1.3 Important Limitations of Use Fenofibrate at a dose equivalent to 160 mg of fenofibrate tablet was not shown to reduce coronary heart disease morbidity and mortality in a large, randomized controlled trial of patients with type 2 diabetes mellitus [see Warnings and Precautions ( 5.1 )].

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Mortality and coronary heart disease morbidity [see Warnings and Precautions ( 5.1 ) ] • Hepatotoxicity [see Warnings and Precautions ( 5.2) ] • Pancreatitis [ see Warnings and Precautions ( 5.7 ) ] • Hypersensitivity reactions [ see Warnings and Precautions ( 5.9 ) ] • Venothromboembolic disease [ see Warnings and Precautions ( 5.10) ] Adverse reactions > 2% and at least 1% greater than placebo: Abnormal liver tests, increased AST, increased ALT, increased CPK, and rhinitis ( 6 ).

To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc.

at 1-888-943-3210 or 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.

Adverse events reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials, regardless of causality, are listed in Table 1 below.

Adverse events led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with placebo.

Increases in liver function tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.

Table 1.

Adverse Reactions Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials BODY SYSTEM Fenofibrate* Placebo Adverse Reaction (N=439) (N=365) BODY AS A WHOLE Abdominal Pain 4.6 % 4.4 % Back Pain 3.4 % 2.5 % Headache 3.2 % DIGESTIVE 2.7 % Nausea 2.3 % 1.9 % Constipation 2.1 % 1.4 % METABOLIC AND NUTRITIONAL DISORDERS Abnormal Liver Function Tests 7.5 %** 1.4 % Increased ALT 3.0 % 1.6 % Increased CPK 3.0 % 1.4 % Increased AST 3.4 %** 0.5 % RESPIRATORY Respiratory Disorder 6.2% 5.5 % Rhinitis 2.3 % 1.1 % * Dosage equivalent to 160 mg fenofibrate.

** Significantly different from Placebo Urticaria was seen in 1.1% vs.

0%, and rash in 1.4% vs.

0.8% of fenofibrate and placebo patients respectively in controlled trials.

Increases in Liver Enzymes In a pooled analysis of 10 placebo-controlled trials, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate at doses equivalent to 107 mg to 160 mg fenofibrate daily versus 1.1% of patients treated with placebo.

In an 8-week study, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 107 mg to 160 mg fenofibrate daily and was 0% in those receiving dosages equivalent to 54 mg or less fenofibrate daily or placebo.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of fenofibrate.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: myalgia, rhabdomyolysis, pancreatitis, acute renal failure, muscle spasm, hepatitis, cirrhosis,increased total bilirubin, anemia, arthralgia, decreases in hemoglobin, decreases in hematocrit, white blood cell decreases, asthenia, severely depressed HDL-cholesterol levels, and interstitial lung disease.

Photosensitivity reactions have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.