No

Antilipemic Agent (Fibric Acid)

Adjunct to dietary therapy for the treatment of adults with very high elevations of serum triglyceride levels (types IV and V hyperlipidemia) who are at risk of pancreatitis and who do not respond adequately to a determined dietary effort; its efficacy can be enhanced by combination with other hypolipidemic agents that have a different mechanism of action; safety and efficacy may be greater than that of clofibrate; 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)

C

Although teratogenicity and mutagenicity tests in animals have been negative, significant risk has been identified with clofibrate, an agent similar in action to fenofibrate. Use should be avoided, if possible, in pregnant women since the neonatal glucuronide conjugation pathways are immature.

Hypersensitivity to fenofibrate or any component hepatic or severe renal dysfunction including primary biliary cirrhosis and unexplained persistent liver function abnormalities; pre-existing gallbladder disease

Hepatic transaminases can significantly elevate (dose-related). Regular monitoring of liver function tests is required. May cause cholelithiasis. Adjustments in warfarin therapy may be required with concurrent use. Use caution when combining fenofibrate with HMG-CoA reductase inhibitors (may lead to myopathy, rhabdomyolysis). The effect of CAD morbidity and mortality has not been established. Therapy should be withdrawn if an adequate response is not obtained after 2 months of therapy at the maximal daily dose (201 mg). Rare hypersensitivity reactions may occur. Dose adjustment is required for renal impairment and elderly patients. Safety and efficacy in children have not been established.

>10%: Miscellaneous: Infection (18%)

1% to 10%:

Cardiovascular: Arrhythmia (1%, equal to placebo)

Central nervous system: Pain (8%), headache (5%), fatigue (5%), dizziness (2%)

Dermatologic: Rash (6%), pruritus (3%)

Endocrine & metabolic: Decreased libido (2%)

Hepatic: Increased transaminases (6.3%)

Gastrointestinal: Nausea/vomiting (4%), abdominal pain (3%), constipation (3%), flatulence (3%), eructation (1%), diarrhea

Ocular: Eye irritation (2%)

Miscellaneous: Flu-like syndrome (5%)

<1% (Limited to important or life-threatening symptoms - with probable causal relationship): Hepatitis, cholelithiasis, cholecystitis, hepatomegaly, myalgia, myasthenia, rhabdomyolysis, photosensitivity, eczema, allergic pulmonary alveolitis, insomnia, hives, bronchospasm, lichenoid photodermatitis, alopecia, joint pain, myopathy, impotence

Symptoms of overdose include nausea, vomiting, diarrhea, and GI distress; treatment is supportive

Chlorpropamide: May increase risk of hypoglycemia.

Furosemide: Increased blood levels of both in hypoalbuminemia.

HMG-CoA reductase inhibitors (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin) may increase the risk of myopathy and rhabdomyolysis. The manufacturer warns against concomitant use. However, combination therapy with statins has been used in some patients with resistant hyperlipidemias (with great caution).

Rifampin: Decreased fenofibrate blood levels.

Warfarin: Increased hypoprothrombinemic response; monitor INRs closely when fenofibrate is initiated or discontinued.

Fenofibric acid is believed to increase VLDL catabolism by enhancing the synthesis of lipoprotein lipase; 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

Absorption: 60% to 90% when given with meals

Distribution: Distributes well to most tissues except brain or eye; concentrates in liver, kidneys, and gut

Protein binding: >99%

Metabolism: Metabolized to its active form, fenofibric acid, by tissue and plasma esterases; then undergoes inactivation by glucuronidation in the liver or kidneys

Half-life, elimination: 21 hours (30 hours in elderly, 44-54 hours in hepatic impairment)

Time to peak: 4-6 hours

Elimination: 60% to 93% excreted in metabolized form; 5% to 25% excreted fecally; hemodialysis has no effect on removal of fenofibric acid from the plasma

Adults: Initial: 67 mg/day, up to 3 capsules (201 mg)

Total serum cholesterol and triglyceride concentration and CLDL, LDL, and HDL levels should be measured periodically; if only marginal changes are noted in 6-8 weeks, the drug should be discontinued; serum transaminases should be measured every 3 months; if ALT values increase >100 units/L, therapy should be discontinued. Monitor LFTs prior to initiation, at 6 and 12 weeks after initiation of first dose, then periodically thereafter.

Selection of lipid-lowering therapy should be based on the patient's lipid profile, concomitant disease states, and the cost of therapy. Fenofibrate may be particularly useful in those patients with hypertriglyceridemia. A recent study suggests that fenofibrate therapy is associated with an increase in homocyst(e)ine levels. The clinical implications of this finding have not been established.

May rarely cause drowsiness or insomnia

None reported

No information available to require special precautions

No effects or complications reported

Take with food. Do not change dosage without consulting prescriber. Maintain diet and exercise program as prescribed. You may experience mild GI disturbances (eg, gas, diarrhea, constipation, nausea); inform prescriber if these are severe. Report skin rash or irritation, insomnia, unusual muscle pain or tremors, or persistent dizziness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Capsule: 67 mg, 200 mg