(fen oh FYE brik AS id)
Adjunct to dietary therapy for the treatment of severely elevated serum triglyceride levels; adjunct to dietary therapy for the reduction of low density lipoprotein cholesterol (LDL-C), total cholesterol (total-C), triglycerides, and apolipoprotein B (apo B) and to increase high density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia or mixed dyslipidemia
TriLipix ¢ „ ¢ is also indicated as adjunct to dietary therapy concomitantly with a statin to reduce triglyceride levels and increase HDL-C levels in patients with mixed dyslipidemia and coronary heart disease (CHD) or at risk for CHD
Hypersensitivity to fenofibric acid, fenofibrate, or any component of the formulation; hepatic dysfunction including primary biliary cirrhosis and unexplained persistent liver function abnormalities; severe renal impairment (including patients on dialysis); pre-existing gallbladder disease; breast-feeding
Mixed dyslipidemia (coadministered with a statin): Oral: TriLipix ¢ „ ¢: 135 mg once daily (maximum: 135 mg/day)
Hypertriglyceridemia: Oral:
Fibricor ‚ ®: Initial: 35-105 mg once daily; Maintenance: Individualize according to patient response (maximum: 105 mg/day)
TriLipix ¢ „ ¢: Initial: 45-135 mg once daily; Maintenance: Individualize according to patient response (maximum: 135 mg/day)
Primary hypercholesterolemia or mixed dyslipidemia: Oral:
Fibricor ‚ ®: 105 mg once daily (maximum: 105 mg/day)
TriLipix ¢ „ ¢: 135 mg once daily (maximum: 135 mg/day)
Oral: Dosage based on renal function
Normal renal function:
Fibricor ‚ ®: CrCl >80 mL/minute: No dosage adjustment necessary
TriLipix ¢ „ ¢: eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
Mild-to-moderate renal impairment
Fibricor ‚ ®: CrCl 30-80 mL/minute: Initial: 35 mg once daily
TriLipix ¢ „ ¢: eGFR 30-59 mL/minute/1.73 m2: Initial: 45 mg once daily
Severe renal impairment (with or without dialysis):
Fibricor ‚ ®: CrCl <30 mL/minute: Use is contraindicated.
TriLipix ¢ „ ¢: eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
Use is contraindicated in active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities.
May be administered with or without food. Capsule: Swallow whole; do not open, break, chew, crush, or dissolve. When coadministered with a statin for mixed lipidemia, for convenience, may administer at the same time of day as the statin.
May be taken with or without food. Patients should follow appropriate lipid-lowering diet.
Fibricor: Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from light and moisture.
Trilipix: Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light and moisture.
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. Consider therapy modification
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy
Chenodiol: Fibric Acid Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any fibric acid derivative. Monitor therapy
Colchicine: Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. Monitor therapy
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. Consider therapy modification
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy
Ezetimibe: Fibric Acid Derivatives may increase the serum concentration of Ezetimibe. Monitor therapy
HMG-CoA Reductase Inhibitors: Fenofibric Acid may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Sulfonylureas: Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Tacrolimus (Systemic): May enhance the nephrotoxic effect of Fenofibric Acid. Monitor therapy
Ursodiol: Fibric Acid Derivatives may diminish the therapeutic effect of Ursodiol. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification
Warfarin: Fenofibric Acid may enhance the anticoagulant effect of Warfarin. Fenofibric Acid may increase the serum concentration of Warfarin. Consider therapy modification
Periodic blood counts during first year of therapy; total cholesterol, LDL-C, triglycerides, and HDL-C should be measured periodically; LFTs (including ALT) (baseline and regularly during therapy) and discontinue therapy if levels remain >3 times normal limits; serum creatinine (in patients with or at risk for renal impairment)
Adverse reactions and frequency reported as observed during monotherapy and concurrent administration with a statin (HMG-CoA reductase inhibitor).
>10%: Central nervous system: Headache (12% to 13%)
1% to 10%:
Central nervous system: Dizziness (3% to 4%), pain (1% to 4%), fatigue (2% to 3%)
Gastrointestinal: Nausea (4% to 6%), dyspepsia (3% to 5%), diarrhea (3% to 4%), constipation (3%)
Hepatic: Increased serum ALT (monotherapy: 1%; coadministered with statin: 3%)
Neuromuscular & skeletal: Back pain (4% to 6%), limb pain (3% to 5%), arthralgia (4%), myalgia (3% to 4%), muscle spasm (2% to 3%)
Respiratory: Nasopharyngitis (4% to 5%), upper respiratory tract infection (4% to 5%), sinusitis (3% to 4%)
Additional adverse reactions when fenofibric acid coadministered with a statin (frequency not defined): Bronchitis, cough, hypertension, increased creatine phosphokinase, increased liver enzymes, increased serum AST, influenza, insomnia, musculoskeletal pain, pharyngolaryngeal pain, urinary tract infection
Postmarketing and/or case reports (seen with fenofibrate) (Limited to important or life-threatening): Agranulocytosis, anemia, cholecystitis, cirrhosis, decreased HDL cholesterol, decreased hematocrit, decreased hemoglobin, decreased white blood cell count, deep vein thrombosis, hepatitis (including hepatocellular, chronic active, and cholestatic hepatitis), homocysteinemia, increased creatine phosphokinase, increased serum creatinine, pancreatitis, pulmonary embolism, renal failure, rhabdomyolysis, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
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).
Concerns related to adverse effects:
- Cholelithiasis: May cause cholelithiasis; discontinue if gallstones found upon gallbladder studies.
- HDL cholesterol (HDL-C): A paradoxical, severe, and reversible decrease in HDL-C (as low as 2 mg/dL) with a simultaneous decrease in apolipoprotein A1 has been reported within 2 weeks to years after initiation of fibrate therapy. Monitor HDL-C within a few months of initiation of therapy and discontinue if HDL-C becomes severely depressed; do not restart therapy.
- 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.
- 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, those receiving concomitant HMG-CoA reductase inhibitors or colchicine, and patients with diabetes mellitus, renal failure, or hypothyroidism. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
- Renal effects: Reversible increases in serum creatinine (>2 mg/dL) have been observed with use; no adverse effects on clinical outcomes (ie, adverse renal or cardiovascular outcomes) seen in one analysis (Bonds, 2012). Fenofibrate has been shown to increase creatinine production (unknown mechanism) resulting in an equal increase of creatinuria demonstrating that the increase does not reflect a reduction in creatinine clearance (Hottelart, 2002). 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 including those receiving dialysis.
Concurrent drug therapy issues:
- Anticoagulants: Use with caution in patient taking oral anticoagulants (eg, warfarin); adjustments in therapy may be required.
- HMG-CoA reductase inhibitors: Use caution with HMG-CoA reductase inhibitors; may lead to myopathy, rhabdomyolysis. No incremental benefit of combination therapy on cardiovascular morbidity and mortality over statin monotherapy has been established. In combination with HMG-CoA reductase inhibitors, fenofibric acid derivatives are generally regarded as safer than gemfibrozil due to limited pharmacokinetic interaction.
Special populations:
- Elderly: Due to a higher incidence of renal impairment, use with caution in the elderly; dosage adjustment based on renal function may be required.
- Type 2 diabetes mellitus: In two large randomized controlled clinical trials, neither fenofibrate monotherapy (Keech, 2005) nor the addition of fenofibrate to simvastatin (ACCORD Study Group, 2010) compared to placebo has been shown to reduce cardiovascular disease morbidity and mortality in patients with type 2 diabetes. The implications of these trials are thought to apply to fenofibric acid as well.
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.
C
Adverse events were observed in animal reproduction studies. When treatment is required during pregnancy, other agents are preferred (NCEP, 2002).
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 increased in HDL occurs in some hypertriglyceridemia patients.
Well absorbed
Fenofibric acid (active form) undergoes inactivation by glucuronidation. The choline salt dissociates in the GI tract to form fenofibric acid (free acid)
Urine (as fenofibric acid and fenofibric acid glucuronide)
Fibricor ‚ ®: ~ 2.5 hours; TriLipix ¢ „ ¢: 4-5 hours
~20 hours
~99%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, dyspepsia, pyrosis, or nausea. Have patient report immediately to prescriber severe asthenia, considerable fatigue, inability to eat, discolored urine, jaundice, or rash (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.