DESCRIPTION
id: e72d8fff-744c-40bd-bfbe-360c9e674524
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Fenofibrate tablets are a lipid regulating agent available as tablets for oral administration. Each tablet contains 160 mg of fenofibrate. The chemical name for fenofibrate is 2-[4-(4-chlorobenzoyl) phenoxy]-2-methylpropanoic acid, 1-methylethyl ester with the following structural formula:
The empirical formula is C20H21O4Cl and the molecular weight is 360.83; fenofibrate is insoluble in water. The melting point is 79 to 82°C. Fenofibrate is a white solid which is stable under ordinary conditions.
CLINICAL PHARMACOLOGY
id: 3c08cd90-3b7b-471e-862f-41592fef98b1
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
A variety of clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B), an LDL membrane complex, are associated with human atherosclerosis. Similarly, decreased levels of high density lipoprotein cholesterol (HDL-C) and its transport complex, apolipoprotein A (apo AI and apo AII) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C, LDL-C, and triglycerides, and inversely with the level of HDL-C. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of cardiovascular morbidity and mortality has not been determined.
Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apoproteins apoAI and apoAII.
The 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, fenofibrate increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity).
The resulting fall in triglycerides 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 apoproteins A-I, A-II and HDL-cholesterol.
Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.
CONTRAINDICATIONS
id: a6f490ee-26a7-44a4-b072-04dd8dba6820
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Fenofibrate tablets are contraindicated in patients who exhibit hypersensitivity to fenofibrate.
Fenofibrate tablets are contraindicated in patients with hepatic or severe renal dysfunction, including primary biliary cirrhosis, and patients with unexplained persistent liver function abnormality.
Fenofibrate tablets are contraindicated in patients with preexisting gallbladder disease (see
WARNINGS
).
ADVERSE REACTIONS
id: 9d844182-3a2a-4490-941a-7f52ed6ad065
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse events reported by 2% or more of patients treated with fenofibrate during the double-blind, placebo-controlled trials, regardless of causality, are listed in the table 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.
| BODY SYSTEM |
FenofibrateDosage equivalent to 145 mg fenofibrate tablets.
|
Placebo |
| Adverse Event |
(N=439) |
(N=365) |
|
BODY AS A WHOLE
|
| Abdominal Pain |
4.6% |
4.4% |
| Back Pain |
3.4% |
2.5% |
| Headache |
3.2% |
2.7% |
| Asthenia |
2.1% |
3.0% |
| Flu Syndrome |
2.1% |
2.7% |
|
DIGESTIVE
|
| Liver Function Test Abnormal |
7.5%Significantly different from Placebo.
|
1.4% |
| Diarrhea |
2.3% |
4.1% |
| Nausea |
2.3% |
1.9% |
| Constipation |
2.1% |
1.4% |
|
METABOLIC AND NUTRITIONAL DISORDERS
|
| SGPT Increased |
3.0% |
1.6% |
Creatine Phophokinase
Increased |
3.0% |
1.4% |
| SGOT Increased |
3.4%
|
0.5% |
|
RESPIRATORY
|
| Respiratory Disorder |
6.2% |
5.5% |
| Rhinitis |
2.3% |
1.1% |
Additional adverse events reported during post-marketing surveillance or by three or more patients in placebo-controlled trials or reported in other controlled or open trials, regardless of causality are listed below.
BODY AS A WHOLE: Accidental injury, allergic reaction, chest pain, cyst, fever, hernia, infection, malaise and pain (unspecified).
CARDIOVASCULAR SYSTEM: Angina pectoris, arrhythmia, atrial fibrillation, cardiovascular disorder, coronary artery disorder, electrocardiogram abnormal, extrasystoles, hypertension, hypotension, migraine, myocardial infarct, palpitation, peripheral vascular disorder, phlebitis, tachycardia, varicose vein, vascular disorder, vasodilatation, venous thromboembolic events (deep vein thrombosis, pulmonary embolus) and ventricular extrasystoles.
DIGESTIVE SYSTEM: Anorexia, cholecystitis, cholelithiasis, colitis, diarrhea, duodenal ulcer, dyspepsia, eructation, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal disorder, increased appetite, jaundice, liver fatty deposit, nausea, pancreatitis, peptic ulcer, rectal disorder, rectal hemorrhage, tooth disorder and vomiting.
ENDOCRINE SYSTEM: Diabetes mellitus.
HEMIC AND LYMPHATIC SYSTEM: Anemia, ecchymosis, eosinophilia, leukopenia, lymphadenopathy, and thrombocytopenia.
LABORATORY INVESTIGATIONS: Alkaline phosphatase increased, bilirubin increased, blood urea nitrogen increased, serum creatinine increased, gamma glutamyl transpeptidase increased, lactate dehydrogenase increased, SGOT and SGPT increased.
METABOLIC AND NUTRITIONAL DISORDERS: Edema, gout, hyperuricemia, hypoglycemia, peripheral edema, weight gain, and weight loss.
MUSCULOSKELETAL SYSTEM: Arthralgia, arthritis, arthrosis, bursitis, joint disorder, leg cramps, myalgia, myasthenia, myositis, rhabdomyolysis and tenosynovitis.
NERVOUS SYSTEM: Anxiety or nervousness, depression, dizziness, dry mouth, hypertonia, insomnia, libido decreased, neuralgia, paresthesia, somnolence and vertigo.
RESPIRATORY SYSTEM: Allergic pulmonary alveolitis, asthma, bronchitis, cough increased, dyspnea, laryngitis, pharyngitis, pneumonia and sinusitis.
SKIN AND APPENDAGES: Acne, alopecia, contact dermatitis, eczema, fungal dermatitis, herpes simplex, herpes zoster, maculopapular rash, nail disorder, photosensitivity reaction, pruritus, rash, sweating, skin disorder, skin ulcer and urticaria.
SPECIAL SENSES: Abnormal vision, amblyopia, cataract specified, conjunctivitis, ear pain, eye disorder, otitis media and refraction disorder.
UROGENITAL SYSTEM: Abnormal kidney function, cystitis, dysuria, gynecomastia, prostatic disorder, unintended pregnancy, urinary frequency, urolithiasis and vaginal moniliasis.
OVERDOSAGE
id: d82321bc-932d-4bf4-8a46-4c2902fd7b35
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
There is no specific treatment for overdose with fenofibrate tablets. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because fenofibrate is highly bound to plasma proteins, hemodialysis should not be considered.
DOSAGE AND ADMINISTRATION
id: cf8d2351-fca7-4776-a4ee-081fb583f5a7
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablets, and should continue this diet during treatment with fenofibrate tablets. Fenofibrate tablets can be given without regard to meals.
For the treatment of adult patients with primary hypercholesterolemia or mixed hyperlipidemia, the initial dose of fenofibrate tablets is 145 mg per day.
For adult patients with hypertriglyceridemia, the initial dose is 48 to 145 mg per day. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 145 mg per day.
Treatment with fenofibrate tablets should be initiated at a dose of 48 mg/day in patients having having mild to moderately impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose.
Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate tablets if lipid levels fall significantly below the targeted range.
HOW SUPPLIED
id: 7ee0f654-bcc8-4adf-97c8-13b690fab753
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Fenofibrate tablet, 160 mg are white to off-white, film-coated, modified capsule shaped tablets, debossed with “G352” on one side and plain on the other side.
NDC 0179-0091-80 Bottle of 2160 Tablets
Fenofibrate tablet, 54 mg are yellow, film-coated, oval shape tablets debossed with “G” on one side and “351” on the other side.
NDC 0179-0103-80 Bottle of 2160 Tablets
REFERENCES
id: 902087de-90b2-4ab3-bf17-808f34a878aa
displayName: REFERENCES SECTION
FDA Article Code: 34093-5
- GOLDBERG AC, et al. Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias: A Double-Blind, Placebo-Controlled Multicenter US Study. Clinical Therapeutics, 11, pp. 69 – 83, 1989.
- NIKKILA EA. Familial Lipoprotein Lipase Deficiency and Related Disorders of Chylomicron Metabolism. In Stanbury J.B., et al. (eds.): The Metabolic Basis of Inherited Disease, 5th edition, McGraw-Hill, 1983, Chap. 30, pp. 622 – 642.
- BROWN WV, et al. Effects of Fenofibrate on Plasma Lipids: Double-Blind, Multicenter Study In Patients with Type IIA or IIB Hyperlipidemia. Arteriosclerosis. 6, pp. 670 – 678, 1986.
PRINCIPAL DISPLAY PANEL – 160 mg Tablet Bottle Label
id: af083a9f-78d8-4e97-85a7-cba406df32c6
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 0179-0091-80
Fenofibrate
Tablets
160 mg
Rx only
2160 Tablets
PRINCIPAL DISPLAY PANEL – 54 mg Tablet Bottle Label
id: 3b710a7a-0e05-4b0a-9019-a34cd1507328
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 0179-0103-80
Fenofibrate
Tablets
54 mg
Rx only
2160 Tablets
