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Medication Safety Issues
Sound-alike/look-alike issues:
TriCor® may be confused with Fibricor®, Tracleer®
Pronunciation
(fen oh FYE brate)
U.S. Brand Names
Index Terms
Generic Available
Yes: Micronized capsule and tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Adjunct to dietary therapy for the treatment of adults with elevations of serum triglyceride levels (types IV and V hyperlipidemia); adjunct to dietary therapy for the reduction of low density lipoprotein cholesterol (LDL-C), total cholesterol (total-C), triglycerides, and apolipoprotein B (apo B) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson types IIa and IIb)
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have shown embryocidal and teratogenic effect. There are no adequate and well-controlled studies in pregnant women. Use should be avoided, if possible, in pregnant women since the neonatal glucuronide conjugation pathways are immature.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Tumor formation was observed in animal studies; nursing is not recommended if the medication cannot be discontinued.
Contraindications
Hypersensitivity to fenofibrate or any component of the formulation; hepatic dysfunction including primary biliary cirrhosis and unexplained persistent liver function abnormalities; severe renal dysfunction; pre-existing gallbladder disease; breast-feeding (only Fenoglide™)
Canadian labeling: Additional contraindications (not in U.S. labeling): Pregnancy; breast-feeding; known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen; allergy to soya lecithin or peanut or arachis oil
Warnings/Precautions
Concerns related to adverse effects:
• Cholelithiasis: May cause cholelithiasis; discontinue if gallstones are found upon gallbladder studies.
• Hemogloblin/hematocrit/WBC effects: May cause mild-to-moderate decreases in hemoglobin, hematocrit and WBC upon initiation of therapy which usually stabilizes with long-term therapy. Agranulocytosis and thrombocytopenia have rarely been reported. Periodic monitoring of blood counts is recommended during the first year of therapy.
• Hepatic effects: Hepatic transaminases can become significantly elevated (dose-related); hepatocellular, chronic active, and cholestatic hepatitis have been reported. Regular monitoring of liver function tests is required.
• Hypersensitivity reactions: Rarely hypersensitivity reactions (eg, severe skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis) may occur.
• Myopathy/rhabdomyolysis: Has been associated with rare myositis or rhabdomyolysis; patients should be monitored closely. Risk increased in the elderly, patients with diabetes mellitus, renal failure, or hypothyroidism. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
• Renal effects: Increases in serum creatinine (>2 mg/dL) have been observed with use; monitor renal function in patients with renal impairment and consider monitoring patients with increased risk for developing renal impairment.
• Venous thromboembolism (VTE): Use has been associated with pulmonary embolism (PE) and deep vein thrombosis (DVT). Use with caution in patients with risk factors for VTE.
Disease-related concerns:
• Renal impairment: Use with caution in patients with mild-to-moderate renal impairment; dosage adjustment required. Contraindicated with severe renal impairment.
Concurrent drug therapy issues:
• Anticoagulants: Use with caution in patient taking oral anticoagulants (eg, warfarin); adjustments in anticoagulation therapy may be required.
• HMG-CoA reductase inhibitors: Use caution with HMG-CoA reductase inhibitors; may lead to myopathy, rhabdomyolysis. In combination with HMG-CoA reductase inhibitors, fenofibrate is generally regarded as safer than gemfibrozil due to limited pharmacokinetic interaction with statins.
Special populations:
• Elderly: Due to a higher incidence of renal impairment, use with caution in the elderly; dosage adjustment required.
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
• Optimal response: Therapy should be withdrawn if an adequate response is not obtained after 2-3 months of therapy at the maximal daily dose. In patients with severe hypertriglyceridemia, the occurrence of pancreatitis may represent a failure of efficacy.
Adverse Reactions
>10%: Hepatic: Liver function tests increased (dose related; 3% to 13%)
1% to 10%:
Central nervous system: Headache (3%)
Gastrointestinal: Abdominal pain (5%), constipation (2%), nausea (2%)
Neuromuscular & skeletal: Back pain (3%), CPK increased (3%)
Respiratory: Respiratory disorder (6%), rhinitis (2%)
Postmarketing and/or case reports (limited to important or life-threatening): Abnormal vision, agranulocytosis, alkaline phosphatase decreased, allergic reaction, alopecia, amblyopia, anemia, angina pectoris, anorexia, anxiety, appetite increased, arrhythmia, arthralgia, arthritis, arthrosis, asthma, atrial fibrillation, bronchitis, bruising, bursitis, cataract, cholecystitis, cholelithiasis, cholestatic hepatitis, cirrhosis, colitis, conjunctivitis, contact dermatitis, cough, creatinine increased, cyst, cystitis, deep venous thrombosis, depression, diabetes mellitus, diaphoresis, diarrhea, dizziness, dyspepsia, dyspnea, dysuria, ear pain, eczema, edema, electrocardiogram abnormality, eosinophilia, esophagitis, extrasystoles, fatty liver deposits, fever, flatulence, fungal dermatitis, gastritis, gastroenteritis, gout, gynecomastia, hepatitis, herpes simplex, herpes zoster, hyper-/hypotension, hypersensitivity reaction, hypertonia, hyperuricemia, hypoglycemia, infection, insomnia, kidney function abnormality, laryngitis, leg cramps, leukopenia, libido decreased, lymphadenopathy, maculopapular rash, malaise, MI, migraine, myalgia, myasthenia, myopathy, myositis, nervousness, neuralgia, otitis media, pain, palpitation, pancreatitis, paresthesia, peptic ulcer, peripheral edema, peripheral vascular disorder, pharyngitis, phlebitis, photosensitivity reaction, pneumonia, pregnancy (unintended), prostate disorder, pruritus, pulmonary embolus, rash, rectal hemorrhage, refraction disorder, rhabdomyolysis, sinusitis, skin ulcer, somnolence, Stevens-Johnson syndrome, tachycardia, tenderness, tenosynovitis, thrombocytopenia, toxic epidermal necrolysis, urea in creased, urinary frequency, urolithiasis, urticaria, vaginal moniliasis, varicose veins, vasodilatation, vertigo, vomiting, weakness, weight gain/loss, xerostomia
Metabolism/Transport Effects
Substrate of CYP3A4 (minor); Inhibits CYP2A6 (weak), 2C8 (weak), 2C9 (weak), 2C19 (weak)
Drug Interactions
Bile Acid Sequestrants: May decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Exceptions: Colesevelam. Risk D: Consider therapy modification
Colchicine: Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. Risk C: Monitor therapy
CycloSPORINE: May enhance the nephrotoxic effect of Fibric Acid Derivatives. Fibric Acid Derivatives may decrease the serum concentration of CycloSPORINE. Management: Careful consideration of the risks and benefits should be undertaken prior to use of this combination; extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary. Risk D: Consider therapy modification
CycloSPORINE, Systemic: May enhance the nephrotoxic effect of Fibric Acid Derivatives. Fibric Acid Derivatives may decrease the serum concentration of CycloSPORINE, Systemic. Management: Careful consideration of the risks and benefits should be undertaken prior to use of this combination; extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary. Risk D: Consider therapy modification
Ezetimibe: Fibric Acid Derivatives may increase the serum concentration of Ezetimibe. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Fenofibrate may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy
Sulfonylureas: Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Warfarin: Fenofibrate may enhance the anticoagulant effect of Warfarin. Fenofibrate may increase the serum concentration of Warfarin. Risk D: Consider therapy modification
Storage
Store at 15°C to 30°C (59°F to 86°F). Protect from light and moisture. Store tablets in moisture-protective container.
Mechanism of Action
Fenofibric acid, an agonist for the nuclear transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-alpha), downregulates apoprotein C-III (an inhibitor of lipoprotein lipase) and upregulates the synthesis of apolipoprotein A-I, fatty acid transport protein, and lipoprotein lipase resulting in an increase in VLDL catabolism, fatty acid oxidation, and elimination of triglyceride-rich particles; as a result of a decrease in VLDL levels, total plasma triglycerides are reduced by 30% to 60%; modest increase in HDL occurs in some hypertriglyceridemic patients.
Pharmacodynamics/Kinetics
Absorption: Increased when taken with meals
Distribution: Widely to most tissues
Protein binding: >99%
Metabolism: Tissue and plasma via esterases to active form, fenofibric acid; undergoes inactivation by glucuronidation hepatically or renally
Half-life elimination: Fenofibric acid: Mean: 20 hours (range: 10-35 hours)
Time to peak: 3-8 hours
Excretion: Urine (60% as metabolites); feces (25%); hemodialysis has no effect on removal of fenofibric acid from plasma
Dosage
Oral:
Adults:
Hypertriglyceridemia: Initial:
Antara® (micronized): 43-130 mg/day; maximum dose: 130 mg/day
Fenoglide™: 40-120 mg/day; maximum dose: 120 mg/day
Lipidil EZ® [CAN; not available in U.S.]: 145 mg/day; maximum dose: 145 mg/day
Lipidil Micro® [CAN; not available in U.S.]: 200 mg/day; maximum dose: 200 mg/day
Lipidil Supra® [CAN; not available in U.S.]: 160 mg/day; maximum dose: 200 mg/day
Lipofen®: 50-150 mg/day; maximum dose: 150 mg/day
Lofibra® (micronized): 67-200 mg/day with meals; maximum dose: 200 mg/day
Lofibra® (tablets): 54-160 mg/day; maximum dose: 160 mg/day
TriCor®: 48-145 mg/day; maximum dose: 145 mg/day
Triglide™: 50-160 mg/day; maximum dose: 160 mg/day
Hypercholesterolemia or mixed hyperlipidemia:
Antara® (micronized): 130 mg/day
Fenoglide™: 120 mg/day
Lipidil EZ® [CAN; not available in U.S.]: 145 mg/day; maximum dose: 145 mg/day
Lipidil Micro® [CAN; not available in U.S.]: 200 mg/day; maximum dose: 200 mg/day
Lipidil Supra® [CAN; not available in U.S.]: 160 mg/day; maximum dose: 200 mg/day
Lipofen®: 150 mg/day
Lofibra® (micronized): 200 mg/day
Lofibra® (tablets): 160 mg/day
TriCor®: 145 mg/day
Triglide™: 160 mg/day
Elderly: Initial:
Antara® (micronized): 43 mg/day
Fenoglide™: Adjust dosage based on creatinine clearance
Lipidil EZ® [CAN; not available in U.S.]: 48 mg/day
Lipidil Micro® [CAN; not available in U.S.]: Adjust dosage based on creatinine clearance
Lipidil Supra® [CAN; not available in U.S.]: Adjust dosage based on creatinine clearance
Lipofen®: 50 mg/day
Lofibra® (micronized): 67 mg/day
Lofibra® (tablets): 54 mg/day
TriCor®: Adjust dosage based on creatinine clearance
Triglide™: 50 mg/day
Dosage adjustment/interval in renal impairment: Monitor renal function and lipid panel before adjusting. Decrease dose or increase dosing interval for patients with renal failure: Note: Use in severe renal impairment is contraindicated (see specific product labeling):
Antara® (micronized): 43 mg/day
Fenoglide™: Clcr 31-80 mL/minute: 40 mg/day
Lipidil EZ® [CAN; not available in U.S.]: Clcr ?20-50 mL/minute: 48 mg/day
Lipidil Micro® [CAN; not available in U.S.]: Clcr ?20-100 mL/minute: 67 mg/day; Note: Lipidil Micro® 67 mg capsules are discontinued in Canada. Micronized formulation at this dosage strength is available through other manufacturers in Canada.
Lipidil Supra® [CAN; not available in U.S.]: Clcr ?20-100 mL/minute: 100 mg/day
Lipofen®: 50 mg/day
Lofibra® (micronized): 67 mg/day
Lofibra® (tablets): 54 mg/day
TriCor®: Clcr 31-80 mL/minute: 48 mg/day
Triglide™: 50 mg/day
Administration: Oral
6-8 weeks of therapy is required to determine efficacy.
Fenoglide™, Lofibra® (capsules [micronized] and tablets), Lipofen®: Administer with meals.
Antara®, TriCor®: May be administered with or without food.
Triglide™: Do not consume chipped or broken tablets. May be administered with or without food.
Canadian products [not available in U.S.]:
Lipidil Micro®, Lipidil Supra®: Administer with meals.
Lipidil EZ®: May be administered with or without food.
Monitoring Parameters
Periodic blood counts during first year of therapy. Total cholesterol, LDL-C, triglycerides, and HDL-C should be measured periodically; If only marginal changes are noted in 6-8 weeks, the drug should be discontinued. Monitor LFTs regularly and discontinue therapy if levels remain >3 times normal limits.
Dietary Considerations
Fenoglide™, Lofibra® (capsules [micronized] and tablets), Lipofen®: Take with meals.
Antara®, TriCor®, Triglide™: May be taken with or without food.
Canadian products [not available in U.S.]:
Lipidil Micro®, Lipidil Supra®: Take with meals.
Lipidil EZ® : May be taken with or without food.
Patient Education
Do not take any new prescription or OTC medications or herbal products during therapy without consulting prescriber. Take exactly as directed. Do not change dosage, dosage form, or frequency without consulting prescriber. Maintain diet and exercise program as prescribed. If you are a diabetic taking a sulfonylurea, monitor blood sugars closely; this medication may alter the effects of your antidiabetic medication. You may experience mild GI disturbances (eg, gas, diarrhea, constipation, nausea); inform prescriber if these are severe. Report immediately unusual muscle pain or weakness; skin rash or irritation; insomnia; persistent dizziness; chest pain or palpitations; difficult respirations; pain, swelling, redness, or heat in extremities; or any other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
The definition of and, therefore, when to treat hyperlipidemia in the elderly is a controversial issue. The National Cholesterol Education Program recommends that all adults maintain a plasma cholesterol <160 mg/dL. Older adults with one additional risk factor, goal LDL would be <130 mg/dL. It is the authors' belief that pharmacologic treatment be reserved for those who are unable to obtain a desirable plasma cholesterol concentration by diet alone and for whom the benefits of treatment are believed to outweigh the potential adverse effects, drug interactions, and cost of treatment.
Cardiovascular Considerations
Fibric acids decrease triglycerides (TGs) by 20% to 50%, and increase HDL-cholesterol (HDL-C) by 10% to 20%. They decrease LDL-cholesterol (LDL-C) by 5% to 20%, however, LDL-C actually may increase by 10% to 30% when fibrates are initiated in patients with high TGs (>400 mg/dL). Although combination therapy with statins has been used in patients with resistant hyperlipidemias, keep vigilant for signs and symptoms of myopathy.
The combination of ezetimibe and fenofibrate is FDA approved for treatment of mixed hyperlipidemia. Dosing regimen approved: Ezetimibe 10 mg and fenofibrate 160 mg once daily.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Dry mouth and tooth disorder.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause drowsiness or insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Use caution and monitor closely in presence of hepatic or renal dysfunction, gallbladder disease, and advanced age. Assess potential for interactions with other pharmacological agents the patient may be taking (eg, coumarin anticoagulants). Evaluate results of laboratory tests (LFTs and blood counts) on a regular basis throughout therapy. Assess therapeutic effectiveness and patient response (eg, myopathy, rhabdomyolysis, arrhythmias, gastrointestinal upset, CNS changes, hypoglycemia, myalgia). Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule:
Lipofen®: 50 mg; 100 mg [DSC]; 150 mg
Capsule [micronized]: 67 mg, 134 mg, 200 mg
Antara®: 43 mg, 130 mg
Lofibra®: 67 mg, 134 mg, 200 mg
Tablet: 54 mg, 160 mg
Fenoglide™: 40 mg, 120 mg
Lofibra®: 54 mg, 160 mg
TriCor®: 48 mg, 145 mg [contains soybean lecithin]
Triglide™: 50 mg, 160 mg [contains egg lecithin]
Pricing: U.S. (www.drugstore.com)
Capsules (Antara)
43 mg (30): $56.69
130 mg (30): $138.87
Capsules (Fenofibrate Micronized)
134 mg (100): $146.99
200 mg (30): $69.29
Capsules (Lipofen)
150 mg (90): $255.97
Capsules (Lofibra)
67 mg (30): $37.79
134 mg (30): $60.89
200 mg (30): $89.32
Tablets (Fenofibrate)
54 mg (90): $64.99
160 mg (30): $67.99
Tablets (Fenoglide)
120 mg (30): $135.99
Tablets (Lofibra)
160 mg (30): $88.19
Tablets (Tricor)
48 mg (30): $49.04
145 mg (30): $130.05
Tablets (Triglide)
160 mg (30): $173.98
References
de Lorgeril M, Salen O, Paillard F, et al, “Lipid-Lowering Drugs and Homocyst(e)ine,” Lancet, 1999, 353(9148):209-10.
“Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III),” JAMA, 2001, 285(19):2486-97.
Farnier M, Bonnefous F, Debbas N, et al, “Comparative Efficacy and Safety of Micronized Fenofibrate and Simvastatin in Patients With Primary Type IIa or IIb Hyperlipidemia,” Arch Intern Med, 1994, 154(4):441-9.
Mahley RW and Bersot TP, “Drug Therapy for Hypercholesterolemia and Dyslipidemia,” Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed, Hardman JE and Limbird LE, eds, New York, NY: McGraw-Hill, 2001, 993-5.
Sitori CR, Montanari G, Gianfranceschi G, et al, “Correlation Between Plasma Levels of Fenofibrate and Lipoprotein Changes in Hyperlipidaemic Patients,” Eur J Clin Pharmacol, 1985, 28(6):619-24.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2010
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