CLINICAL: 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. * Dosage equivalent to 150 mg LIPOFEN™ ** Significantly different from Placebo BODY SYSTEMFenofibrate*Placebo Adverse Event(N=439)(N=365) BODY AS A WHOLE Abdominal Pain4.6%4.4% Back Pain3.4%2.5% Headache3.2%2.7% Asthenia2.1%3.0% Flu Syndrome2.1%2.7% DIGESTIVE Liver Function Tests Abnormal7.5%**1.4% Diarrhea2.3%4.1% Nausea2.3%1.9% Constipation2.1%1.4% METABOLIC AND NUTRITIONAL DISORDERS SGPT Increased3.0%1.6% Creatine Phosphokinase Increased3.0%1.4% SGOT Increased3.4%**0.5% RESPIRATORY Respiratory Disorder6.2%5.5% Rhinitis2.3%1.1% Additional adverse events reported 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: Chest pain, pain (unspecified), infection, malaise, allergic reaction, cyst, hernia, fever, photosensitivity reaction, and accidental injury.CARDIOVASCULAR SYSTEM: Angina pectoris, hypertension, vasodilatation, coronary artery disorder, electrocardiogram abnormal, ventricular extrasystoles, myocardial infarction, peripheral vascular disorder, migraine, varicose vein, cardiovascular disorder, hypotension, palpitation, vascular disorder, arrhythmia, phlebitis, tachycardia, extrasystoles, and atrial fibrillation.DIGESTIVE SYSTEM: Dyspepsia, flatulence, nausea, increased appetite, gastroenteritis, cholelithiasis, rectal disorder, esophagitis, gastritis, colitis, tooth disorder, vomiting, anorexia, gastrointestinal disorder, duodenal ulcer, nausea and vomiting, peptic ulcer, rectal hemorrhage, liver fatty deposit, cholecystitis, eructation, gamma glutamyl transpeptidase, and diarrhea.ENDOCRINE SYSTEM: Diabetes mellitusHEMIC AND LYMPHATIC SYSTEM: Anemia, leukopenia, ecchymosis, eosinophilia, lymphadenopathy, and thrombocytopenia.METABOLIC AND NUTRITIONAL DISORDERS: Creatinine increased, weight gain, hypoglycemia, gout, weight loss, edema, hyperuricemia, and peripheral edema.MUSCULOSKELETAL SYSTEM: Myositis, myalgia, arthralgia, arthritis, tenosynovitis, joint disorder, arthrosis, leg cramps, bursitis, and myasthenia.NERVOUS SYSTEM: Dizziness, insomnia, depression, vertigo, libido decreased, anxiety, paresthesia, dry mouth, hypertonia, nervousness, neuralgia, and somnolence.RESPIRATORY SYSTEM: Pharyngitis, bronchitis, cough increased, dyspnea, asthma, pneumonia, laryngitis, and sinusitis.SKIN AND APPENDAGES: Rash, pruritus, eczema, herpes, zoster, urticaria, acne, sweating, fungal dermatitis, skin disorder, alopecia, contact dermatitis, herpes simplex, maculopapular rash, nail disorder, and skin ulcer.SPECIAL SENSES: Conjunctivitis, eye disorder, amblyopia, ear pain, otitis media, abnormal vision, cataract specified, and refraction disorder.UROGENITAL SYSTEM: Urinary frequency, prostatic disorder, dysuria, kidney function abnormal, urolithiasis, gynecomastia, unintended pregnancy, vaginal moniliasis, and cystitis. To report SUSPECTED ADVERSE REACTIONS, contact Kowa Pharmaceuticals America, Inc.at 1 (877) 334-3464 or FDA at 1 (888) 463-6332 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.
Liver Function: Fenofibrate at doses equivalent to 100 mg to 150 mg LIPOFEN® per day has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)].
In a pooled analysis of 10 placebo-controlled trials, increases to > 3 times the upper limit of normal occurred in 5.3% of patients taking fenofibrate versus 1.1% of patients treated with placebo.When transaminase determinations were followed either after discontinuation of treatment or during continued treatment, a return to normal limits was usually observed.
The incidence of increases in transaminases related to fenofibrate therapy appear to be dose related.
In an 8-week dose ranging study, the incidence of ALT or AST elevations to at least three times the upper limit of normal was 13% in patients receiving dosages equivalent to 100 mg to 150 mg LIPOFEN® per day and was 0% in those receiving dosages equivalent to 50 mg or less LIPOFEN® per day, or placebo.
Hepatocellular, chronic active and cholestatic hepatitis associated with fenofibrate therapy have been reported after exposures of weeks to several years.In extremely rare cases, cirrhosis has been reported in association with chronic active hepatitis.Regular periodic monitoring of liver functions, including serum ALT (SGPT) should be performed for the duration of therapy with LIPOFEN®, and therapy discontinued if enzyme levels persist above three times the normal limit.