Fenofibrate

Pronunciation

Pronunciation: FEN-oh-FYE-brate
Class: Antihyperlipidemic

Trade Names

Antara
- Capsules 43 mg
- Capsules 130 mg

Fenoglide
- Tablets 40 mg
- Tablets 120 mg

Lipofen
- Capsules 50 mg
- Capsules 150 mg

Lofibra
- Capsules 67 mg
- Capsules 134 mg
- Capsules 200 mg
- Tablets 54 mg
- Tablets 160 mg

Tricor
- Tablets 48 mg
- Tablets 145 mg

Triglide
- Tablets 50 mg
- Tablets 160 mg

Trilipix
- Capsules, delayed-release 45 mg
- Capsules, delayed-release 135 mg

Apo-Fenofibrate (Canada)
Apo-Feno-Micro (Canada)
Apo-Feno-Super (Canada)
Fenomax (Canada)
Gen-Fenofibrate Micro (Canada)
Lipidil EZ (Canada)
Lipidil Supra (Canada)
PMS-Fenofibrate Micro (Canada)
Sandoz Fenofibrate S (Canada)

Pharmacology

Decreases plasma levels of triglycerides by decreasing synthesis. Also reduces plasma levels of VLDL cholesterol by reducing its release into the circulation and increasing catabolism. Reduces serum uric acid levels by increasing urinary excretion of uric acid.

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Pharmacokinetics

Absorption

Well absorbed. Absolute bioavailability is approximately 81%. T max within 4 to 5 h.

Distribution

Protein binding is approximately 99%. Steady state is achieved within 8 days.

Metabolism

Primarily conjugated with glucuronic acid. Small amount is reduced to a benzhydrol metabolite.

Elimination

Primarily excreted in the urine (60%) in the form of fenofibric acid and fenofibric acid glucuronide. Approximately 25% is excreted in the feces. Elimination half-life is approximately 20 h.

Special Populations

Renal Function Impairment
Atara , Lipofen , Lofibra , Triglide

In patients with severe renal function impairment (CrCl less than 50 mL/min), Cl of fenofibric acid is greatly reduced; minimize the dosage. In patients with moderate renal function impairment (CrCl 50 to 90 mL/min), no dosage modification is necessary.

Fenoglide , Tricor , Trilipix

Half-life is prolonged in patients with mild to moderate renal function impairment (CrCl 30 to 80 mL/min). There is a 2.7-fold increase in exposure for fenofibrate and an increased accumulation of fenofibric acid during chronic dosing in patients with severe renal function impairment (CrCl less than 30 mL/min).

Hepatic Function Impairment

No pharmacokinetic studies have been conducted.

Elderly

Pharmacokinetic studies indicate that fenofibrate can be used in elderly subjects who have healthy renal function without accumulation of the drug or metabolites.

Indications and Usage

Fenofibrate

Adjunctive therapy to diet to reduce elevated LDL cholesterol, total cholesterol, triglycerides and apolipoprotein B, and to increase HDL cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia (Fredrickson types IIa and IIb). Adjunctive therapy to diet for treatment of hypertriglyceridemia (Fredrickson types IV and V hyperlipidemia).

Fenofibric acid ( Trilipix )

Adjunct to diet in combination with an HMG-CoA reductase inhibitor to reduce triglycerides and increase HDL cholesterol in patients with mixed dyslipidemia and coronary heart disease or a coronary heart disease risk equivalent who are on optimal statin therapy to achieve LDL cholesterol goal; adjunctive therapy to diet to reduce triglycerides in patients with severe hypertriglyceridemia; adjunctive therapy to diet to reduce elevated LDL cholesterol, total cholesterol, triglycerides, and apolipoprotein B, and to increase HDL cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia.

Unlabeled Uses

Hyperuricemia; hypertriglyceridemia associated with HIV lipodystrophy.

Contraindications

Hepatic or severe renal function impairment, including primary biliary cirrhosis; unexplained persistent liver function abnormality; preexisting gallbladder disease; hypersensitivity to fenofibrate.

Dosage and Administration

Coadministration With an HMG-CoA Reductase Inhibitor for Treating Mixed Dyslipidemia
Adults

PO Trilipix 135 mg coadministered with an HMG-CoA reductase inhibitor.

Hypertriglyceridemia
Adults

PO

Antara capsules

Initial dosage is 43 to 130 mg/day (max, 130 mg/day).

Fenoglide tablets

Initial dosage is 40 to 120 mg/day (max, 120 mg/day).

Lipofen capsules

Initial dosage is 50 to 150 mg/day (max, 150 mg/day).

Lofibra capsules

67 to 200 mg/day (max, 200 mg/day).

Lofibra tablets

Initial dosage is 54 to 160 mg/day (max, 160 mg/day).

Tricor tablets

Initial dosage is 48 to 145 mg/day (max, 145 mg/day).

Triglide tablets

Initial dosage is 50 to 160 mg once daily (max, 160 mg/day).

Trilipix capsules

Initial dosage is 45 to 135 mg/day (max, 135 mg/day).

Primary Hypercholesterolemia/Mixed Hyperlipidemia
Adults

PO

Antara capsules

130 mg/day.

Fenofibrate tablets

Initial dosage is 160 mg/day.

Fenoglide tablets

Initial dosage is 120 mg/day.

Lipofen capsules

Initial dosage is 150 mg/day.

Lofibra capsules

200 mg/day.

Lofibra tablets

Initial dosage is 160 mg/day.

Tricor tablets

Initial dosage is 145 mg/day.

Triglide tablets

Initial dosage is 160 mg/day.

Trilipix capsules

Initial dosage is 135 mg/day.

Renal Function Impairment
Adults

PO

Antara capsules

Initial dosage is 43 mg/day.

Fenoglide tablets

Initial dosage is 40 mg/day.

Lipofen capsules

Initial dosage is 50 mg/day.

Lofibra capsules

Initial dosage is 67 mg/day.

Lofibra tablets

Initial dosage is 54 mg/day.

Tricor tablets

Initial dosage is 48 mg/day.

Triglide tablets

Initial dosage is 50 mg/day.

Trilipix capsules

Initial dosage is 45 mg/day.

General Advice

  • Use alone or in combination with other lipid-lowering therapy.
  • Administer prescribed dose with food to increase absorption with Lofibra . Triglide and Tricor may be given without regard to meals.
  • Administer prescribed dose 1 h before or 4 to 6 h after a bile acid sequestrant (eg, cholestyramine).

Storage/Stability

Antara , Fenoglide , Lipofen , Tricor , Trilipix , Triglide

Store at 59° to 86°F. Protect from light and moisture.

Fenofibrate tablets, Lofibra tablets and capsules

Store at 68° to 77°F. Protect from moisture.

Drug Interactions

Anticoagulants, oral (eg, warfarin)

Anticoagulant effect may be increased.

Bile acid sequestrants (eg, cholestyramine)

Reduces absorption of fenofibrate/fenofibric acid. Take fenofibrate/fenofibric acid 1 h before or 4 to 6 h after the bile acid sequestrant.

Cyclosporine

Increases risk of nephrotoxicity.

HMG-CoA reductase inhibitors (eg, lovastatin)

Increased risk of severe myopathy, rhabdomyolysis, and acute renal failure. Unless coprescribed (eg, fenofibric acid), avoid coadministration.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Delayed-release

Headache (13%); dizziness (4%); insomnia (3%); fatigue (2%).

Immediate-release

Headache (3%).

Postmarketing

Asthenia.

EENT

Delayed-release

Nasopharyngitis (4%).

Immediate-release

Rhinitis (2%).

GI

Delayed-release

Diarrhea, dyspepsia, nausea (4%); constipation (3%).

Immediate-release

Abdominal pain (5%); constipation, nausea (2%).

Postmarketing

Abdominal pain, pancreatitis.

Genitourinary

Postmarketing

Acute renal failure, renal failure.

Hepatic

Postmarketing

Cirrhosis, hepatitis.

Hematologic-Lymphatic

Postmarketing

Anemia.

Lab Tests

Delayed-release

Increased ALT (1%).

Immediate-release

Increased ALT, AST, and CPK (3%).

Musculoskeletal

Delayed-release

Back pain (6%); pain in extremities (5%); arthralgia (4%); myalgia (3%).

Immediate-release

Back pain (3%).

Postmarketing

Muscle spasms, rhabdomyolysis.

Respiratory

Delayed-release

Upper respiratory tract infection (5%); sinusitis (3%).

Miscellaneous

Delayed-release

Pain (4%).

Precautions

Monitor

Perform regular periodic monitoring of liver function for duration of therapy. Evaluate serum lipids periodically (eg, 4 to 8 wk) during initial therapy to determine lowest effective dose; withdraw therapy if an adequate response is not achieved after 2 mo of treatment with the max dose. Perform periodic blood cell counts during first 12 mo of therapy.


Pregnancy

Category C .

Lactation

Do not use in breast-feeding women.

Children

Safety and efficacy not established.

Elderly

Use with caution because decreased renal function is more likely in this age group.

Hypersensitivity

Acute hypersensitivity reactions have occurred rarely, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Renal Function

When CrCl is less than 50 mL/min, initiate therapy at lowest dose and increase only after evaluation of the effects on renal function and triglyceride levels at this dose.

Trilipix

Avoid administration in patients with severe renal function impairment (CrCl less than 30 mL/min). Reduce the dose in patients with mild to moderate renal function impairment (CrCl 30 to 80 mL/min).

Hepatic Function

Drug may cause significant increases in serum transaminases. If elevated serum levels develop during treatment, repeat levels more frequently. Discontinue therapy if enzyme levels persist at more than 3 times the normal limit.

Trilipix

Increased serum transaminases have been reported. Discontinue therapy if enzyme levels persist above 3 × ULN.

Cholelithiasis

May increase cholesterol secretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Discontinue therapy if gallstones are found.

Diet

Ensure patient is on a lipid-lowering diet before starting therapy and that diet is continued during treatment.

Hematology

Mild to moderate Hct, Hgb, and WBC decreases have been reported following the initiation of therapy. Rarely, thrombocytopenia and agranulocytosis have been reported.

Myopathy/Myositis

Can be associated with use of fibrates alone, usually in patients with renal function impairment. Consider in any patient with diffuse myalgia, muscle tenderness or weakness, or marked CPK elevations. Discontinue therapy if myopathy/myositis is suspected or diagnosed.

Pancreatitis

Has been reported in patients taking fenofibrate.

Secondary cause of hyperlipidemia

Rule out or treat secondary causes of hypercholesterolemia and hypertriglyceridemia before starting therapy.

Serum creatinine

Reversible elevations in serum creatinine have been reported.

Thromboembolic disease

Pulmonary embolism and deep vein thrombosis have been reported to occur at a higher rate in patients receiving fenofibrate compared with placebo.

Overdosage

Symptoms

Signs and symptoms have not been reported.

Patient Information

  • Advise patient to take each dose of Lofibra with food to increase absorption and lipid-lowering effectiveness.
  • Advise patient who also is taking a bile acid resin (eg, cholestyramine) to take fenofibrate 1 h before or 4 to 6 h after the resin.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform patient that drug helps control, but not does cure, lipid abnormality and to continue taking drug as prescribed if lipid levels are lowered.
  • Advise patient that if a dose is missed to take it as soon as possible, but never to take more than 1 dose of fenofibrate a day.
  • Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
  • Emphasize to patient the importance of dietary changes (eg, increase soluble fiber intake, reduce saturated fat intake, regular exercise, smoking cessation, weight control) on cholesterol control.

Copyright © 2009 Wolters Kluwer Health.

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