Fenofibric Acid
Generic: FENOFIBRIC ACID
Basic Information
Manufacturer
Amneal Pharmaceuticals of New York LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
e73404c5-e0ee-48e9-8b09-7a00d7e18e6c
Indications & Usage
1 INDICATIONS AND USAGE Fenofibric acid delayed-release capsules are indicated as adjunctive therapy to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL).
to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible.
Limitations of Use Markedly elevated levels of serum TG (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 determined [see Warnings and Precautions (5.7) ] .
Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus [see Warnings and Precautions (5.1) and Clinical Studies (14.4)] .
Fenofibric acid delayed-release capsules are a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as adjunct to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL).
( 1 ) to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible.
( 1 ) Limitations of Use: Markedly elevated levels of serum TG (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 determined.
( 1 ) Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus.
( 1 )
to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible.
Limitations of Use Markedly elevated levels of serum TG (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 determined [see Warnings and Precautions (5.7) ] .
Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus [see Warnings and Precautions (5.1) and Clinical Studies (14.4)] .
Fenofibric acid delayed-release capsules are a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as adjunct to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL).
( 1 ) to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible.
( 1 ) Limitations of Use: Markedly elevated levels of serum TG (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 determined.
( 1 ) Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus.
( 1 )
Adverse Reactions
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) ] Hepatoxicity [see Warnings and Precautions (5.2) ] Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.3) ] Increases in Serum Creatinine [see Warnings and Precautions ( 5.4) ] Cholelithiasis [see Warnings and Precautions ( 5.5) ] Increased Bleeding Risk with Coumarin Anticoagulants [see Warnings and Precautions ( 5.6) ] Pancreatitis [see Warnings and Precautions ( 5.7) ] Hematologic Changes [see Warnings and Precautions (5.8) ] Hypersensitivity reactions [see Warnings and Precautions ( 5.9) ] Venothromboembolic disease [see Warnings and Precautions ( 5.10) ] Paradoxical Decreases in HDL Cholesterol Levels [see Warnings and Precautions (5.11) ] Adverse reactions (≥ 2% and greater than placebo): abnormal liver tests, increased AST, increased ALT, increased CPK, and rhinitis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of fenofibric acid has been established in adults with hypertriglyceridemia or primary hyperlipidemia based on adequate and well-controlled trials of other formulations of fenofibrate, referenced below as “fenofibrate” [see Clinical Studies (14) ].
Dosages of fenofibrate used in these trials were comparable to fenofibric acid 135 mg per day [see Clinical Pharmacology (12.3) ].
Adverse reactions reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials are listed in Table 1.
Adverse reactions led to discontinuation of treatment in 5% of patients treated with fenofibrate and in 3% 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 Adverse Reaction Placebo (N =365) Fenofibrate (N = 439) Abnormal Liver Tests 1% 8% Abdominal Pain 4% 5% Increased ALT 2% 3% Increased AST 1% 3% Increased Creatine Phosphokinase 1% 3% Constipation 1% 2% Rhinitis 1% 2% Other Adverse Reactions Urticaria 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 three 12-week, double-blind, controlled studies of fenofibric acid, increases in ALT and AST > 3 times the upper limit of normal on two consecutive occasions occurred in 1.9% and 0.2%, respectively, of patients receiving fenofibric acid 135 mg daily and placebo, without other lipid-altering drugs.
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 either an intermediate or maximum recommended daily dosage of fenofibrate versus 1.1% of patients treated with placebo.
In an 8-week trial, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving an intermediate daily dosage or the maximum recommended daily dosage of fenofibrate and was 0% in those receiving the lowest recommended daily dosage of fenofibrate or placebo [see Warnings and Precautions (5.2) ] .
Clinical trials with fenofibric acid did not include a placebo-control arm.
However, the adverse reaction profile of fenofibric acid was generally consistent with that of fenofibrate.
The following adverse reactions not listed above for fenofibrate were reported in ≥ 3% of patients taking fenofibric acid: Gastrointestinal: Diarrhea, dyspepsia General: Pain Infections : Nasopharyngitis, sinusitis, upper respiratory tract infection Musculoskeletal and Connective Tissue : Arthralgia, myalgia, pain in extremity Nervous System : Dizziness 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval 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.
Blood: Anemia Gastrointestinal: Pancreatitis General: Asthenia Hepatobiliary: Increased total bilirubin, hepatitis, cirrhosis Immune System: Anaphylaxis, angioedema Lipid Disorders: Severely depressed HDL-cholesterol levels Musculoskeletal: Muscle spasms, rhabdomyolysis Renal and Urinary: Acute renal failure Respiratory: Interstitial lung disease Skin and Subcutaneous Tissue: Photosensitivity reactions days to months after initiation.
This may occur in patients who report a prior photosensitivity reaction to ketoprofen.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of fenofibric acid has been established in adults with hypertriglyceridemia or primary hyperlipidemia based on adequate and well-controlled trials of other formulations of fenofibrate, referenced below as “fenofibrate” [see Clinical Studies (14) ].
Dosages of fenofibrate used in these trials were comparable to fenofibric acid 135 mg per day [see Clinical Pharmacology (12.3) ].
Adverse reactions reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials are listed in Table 1.
Adverse reactions led to discontinuation of treatment in 5% of patients treated with fenofibrate and in 3% 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 Adverse Reaction Placebo (N =365) Fenofibrate (N = 439) Abnormal Liver Tests 1% 8% Abdominal Pain 4% 5% Increased ALT 2% 3% Increased AST 1% 3% Increased Creatine Phosphokinase 1% 3% Constipation 1% 2% Rhinitis 1% 2% Other Adverse Reactions Urticaria 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 three 12-week, double-blind, controlled studies of fenofibric acid, increases in ALT and AST > 3 times the upper limit of normal on two consecutive occasions occurred in 1.9% and 0.2%, respectively, of patients receiving fenofibric acid 135 mg daily and placebo, without other lipid-altering drugs.
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 either an intermediate or maximum recommended daily dosage of fenofibrate versus 1.1% of patients treated with placebo.
In an 8-week trial, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving an intermediate daily dosage or the maximum recommended daily dosage of fenofibrate and was 0% in those receiving the lowest recommended daily dosage of fenofibrate or placebo [see Warnings and Precautions (5.2) ] .
Clinical trials with fenofibric acid did not include a placebo-control arm.
However, the adverse reaction profile of fenofibric acid was generally consistent with that of fenofibrate.
The following adverse reactions not listed above for fenofibrate were reported in ≥ 3% of patients taking fenofibric acid: Gastrointestinal: Diarrhea, dyspepsia General: Pain Infections : Nasopharyngitis, sinusitis, upper respiratory tract infection Musculoskeletal and Connective Tissue : Arthralgia, myalgia, pain in extremity Nervous System : Dizziness 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval 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.
Blood: Anemia Gastrointestinal: Pancreatitis General: Asthenia Hepatobiliary: Increased total bilirubin, hepatitis, cirrhosis Immune System: Anaphylaxis, angioedema Lipid Disorders: Severely depressed HDL-cholesterol levels Musculoskeletal: Muscle spasms, rhabdomyolysis Renal and Urinary: Acute renal failure Respiratory: Interstitial lung disease Skin and Subcutaneous Tissue: Photosensitivity reactions days to months after initiation.
This may occur in patients who report a prior photosensitivity reaction to ketoprofen.