Fenofibric Acid
Generic: FENOFIBRIC ACID
Basic Information
Manufacturer
Alembic Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
8ffcb173-095a-4550-84f2-18959ad2aab8
Indications & Usage
1 INDICATIONS AND USAGE Fenofibric acid delayed-release capsules 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 Alembic Pharmaceuticals Limited at 1-866-210-9797 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 delayed-release capsules 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 delayed-release capsules 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 delayed-release capsules, 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 delayed-release capsules 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 delayed-release capsules did not include a placebo-control arm.
However, the adverse reaction profile of fenofibric acid delayed-release capsule 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 delayed-release capsules: 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 Postmarketing 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.
To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 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 delayed-release capsules 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 delayed-release capsules 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 delayed-release capsules, 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 delayed-release capsules 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 delayed-release capsules did not include a placebo-control arm.
However, the adverse reaction profile of fenofibric acid delayed-release capsule 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 delayed-release capsules: 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 Postmarketing 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.