Overview
11 DESCRIPTION Fenofibrate, is a lipid regulating agent available as tablets for oral administration. Each tablet contains 54 mg or 160 mg of fenofibrate. The chemical name for fenofibrate is 2-[4-(4-chlorobenzoyl) phenoxy]-2-methyl-propanoic acid, 1-methylethyl ester with the following structural formula: The empirical formula is C 20 H 21 ClO 4 and the molecular weight is 360.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The active moiety of fenofibrate is fenofibric acid. The pharmacological effects of fenofibric acid in both animals and humans have been extensively studied through oral administration of fenofibrate. The lipid-modifying 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).
Indications
- 1 INDICATIONS AND USAGE Fenofibrate tablet USP 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.
Common Doses
- 160 mg
- 54 mg
Dosage
2 DOSAGE AND ADMINISTRATION Primary hypercholesterolemia or mixed dyslipidemia: Initial dose of 160 mg once daily ( 2.2 ). Severe hypertriglyceridemia: Initial dose of 54 to 160 mg once daily. Maximum dose is 160 mg ( 2.3 ). Renally impaired patients: Initial dose of 54 mg once daily ( 2.4 ). Geriatric patients: Select the dose on the basis of renal function ( 2.5 ). Should be given with meals ( 2.1 ). 2.1 General Considerations Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablet USP, and should continue this diet during treatment with...
Contraindications
- 4 CONTRAINDICATIONS Severe renal dysfunction, including dialysis patients ( 4 , 8.6 , 12.3 ). Active liver disease ( 4 , 5.3 ). Gallbladder disease ( 4 , 5.5 ). Known hypersensitivity to fenofibrate ( 4 ). Nursing mothers ( 4 , 8.2 ). Fenofibrate is contraindicated in: patients with severe renal impairment, including those receiving dialysis [see CLINICAL PHARMACOLOGY ( 12.3 )] . patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities [see WARNINGS AND PRECAUTIONS ( 5.2 )] .
Side Effects
- 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 )] •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 ).
Interactions
- 7 DRUG INTERACTIONS Coumarin anticoagulants: ( 7.1 ). Immunosuppressants: ( 7.2 ). Bile acid resins: ( 7.3 ). 7.1 Coumarin Anticoagulants Potentiation of coumarin-type anticoagulant effects has been observed with prolongation of the PT/INR. Caution should be exercised when coumarin anticoagulants are given in conjunction with fenofibrate. The dosage of the anticoagulants should be reduced to maintain the PT/INR at the desired level to prevent bleeding complications.