FENOFIBRATE

FENOFIBRATe (fen-o-fi'brate) Tricor, Triglide, Lofibra, Antara Classifications: antilipemic; Therapeutic: cholesterol-lowering agent Pregnancy Category: C

Availability

48 mg, 50 mg, 154 mg, 160 mg tablets; 43 mg, 67 mg, 87 mg, 134 mg, 200 mg capsules or 50 mg, 100 mg, 150 mg, 160 mg capsules

Action

Fibric acid derivative with lipid-regulating properties. Lowers plasma triglycerides apparently by inhibiting triglyceride synthesis and, as a result, lowers VLDL production as well as stimulates the catabolism of triglyceride-rich lipoprotein (e.g., VLDL). Produces a moderate increase in HDL cholesterol levels in most patients.

Therapeutic Effect

Effectiveness indicated by reduction in the level of serum triglycerides and VLDL production; interferes with synthesis of serum triglycerides.

Uses

Adjunctive therapy to diet for patients with high triglycerides.

Contraindications

Hypersensitivity to fenofibrate or other fibric acid derivatives (e.g., clofibrate, benzofibrate); liver or severe kidney dysfunction; unexplained liver function abnormality; preexisting hepatic disease; primary biliary cirrhosis; preexisting gallbladder disease; pregnancy (category C); lactation; thrombocytopenia. Safety and efficacy in children <10 y (capsules), <18 y (Tricor tablets) are not established.

Cautious Use

Concomitant therapy with HMG-CoA reductase inhibitors (e.g., lovastatin, pravastatin, simvastatin), oral anticoagulant medications; renal impairment, older adults; history of bleeding disorders; myelosuppression.

Route & Dosage

Hypertriglyceridemia Adult: PO 54 mg q.d. (max: 160 mg/d)

Administration

Oral

• Limit dose to 54 mg/d in older adults or those with impaired kidney function.
• Give at least 1 h before or 4–6 h after cholestyramine.
• Store at 15°–30° C (59°–86° F) in a tightly closed container and protect from light.

Adverse Effects (≥1%)

Body as a Whole: Asthenia, fatigue, infections, flu-like syndrome, localized pain, arthralgia. CNS: Headache, paresthesia, dizziness, insomnia. CV: Arrhythmia. GI: Dyspepsia, eructation, flatulence, nausea, vomiting, abdominal pain, constipation, diarrhea, increased appetite. Respiratory: Cough, rhinitis, sinusitis. Skin: Pruritus, rash. Special Senses: Earache, eye floaters, blurred vision, conjunctivitis, eye irritation, Urogenital: Decreased libido, polyuria, vaginitis.

Interactions

Drug: May potentiate anticoagulant effects of warfarin; combination with an hmg-coa reductase inhibitor (statin) may result in rhabdomyolysis or acute renal failure; cholestyramine, colestipol may decrease absorption (give fenofibrate 1 h before or 4–6 h after bile acid sequestrants); may increase risk of nephrotoxicity of cyclosporine.

Pharmacokinetics

Absorption: Well absorbed from the GI tract; increased with food. Peak: 6–8 h. Distribution: 99% protein bound; excreted in breast milk. Metabolism: Rapidly hydrolyzed by esterases to active metabolite, fenofibric acid. Elimination: 60% in urine, 25% in feces. Half-Life: 20 h.

Nursing Implications

Assessment & Drug Effects

• Lab tests: Periodically monitor lipid levels, liver functions, and CBC with differential.
• Discontinue therapy after 2 mo if adequate lipid reduction is not achieved with the maximum dose of 201 mg/d.
• Assess for muscle pain, tenderness, or weakness and, if present, monitor CPK level. Withdraw drug with marked elevations of CPK or if myopathy is suspected.
• Monitor patients on coumarin-type drugs closely for prolongation of PT/INR.

Patient & Family Education

• Contact physician immediately if any of the following develops: Unexplained muscle pain, tenderness, or weakness, especially with fever or malaise; yellowing of skin or eyes; nausea or loss of appetite; skin rash or hives.
• Inform physician regarding concurrent use of cholestyramine, oral anticoagulants, or cyclosporine.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug