Dosing and uses of Fibricor, Trilipix (fenofibric acid)
Adult dosage forms and strengths
tablet (Fibricor)
- 35mg
- 105mg
capsule, delayed-release (Trilipix)
- 45mg
- 135mg
Hypertriglyceridemia
Indicated as adjunct to diet for severe hypertriglyceridemia (>500 mg/dL)
Fibricor: 35-105 mg PO qDay
Trilipix: 45-135 mg PO qDay
Primary Hypercholesterolemia or Mixed Lipidemia
Indicated as adjunct to diet to reduce elevated LDL-C, Total-C, TG, and Apo B, and to increase HDL-C in patients with primary hypercholesterolemia or mixed dyslipidemia
Fibricor: 105 mg PO qDay
Trilipix: 135 mg PO qDay
Dosage modifications
Renal impairment
- Mild-to-moderate (CrCl 30-80 mL/min): Initiate at lowest available dose and increase only after evaluating effects on renal function and lipid levels
- Severe (CrCl <30 mL/min): Contraindicated
Dosing Considerations
Hypertriglyceridemia: Improving glycemic control in diabetic patients with fasting chylomicronemia will usually obviate the need for pharmacological intervention
Fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in patients with type 2 diabetes mellitus
Indication for use with statins withdrawn by FDA
- April 15, 2016: Based on several large cardiovascular outcome trials including AIM-HIGH, ACCORD, and HPS2-THRIVE, the FDA decided that "scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events"
- Consistent with this conclusion, the FDA has determined that the benefits of fenofibric-acid (delayed-release) capsules (eg, Trilipix) for coadministration with statins no longer outweigh the risks, and the approval for this indication should be withdrawn
Pediatric dosage forms and strengths
Safety and efficacy not established
Fibricor, Trilipix (fenofibric acid) adverse (side) effects
>10%
Headache (11.9-13.1%)
1-10%
Back pain (4.1-6.3%)
Nausea (3.5-5.5%)
Upper respiratory tract infection (3.7-5.3%)
Nasopharyngitis (3.5-4.7%)
Diarrhea (3.1-3.7%)
Myalgia (3.1-3.5%)
Increased AST (3.4%)
Increased ALT (3%)
Increased CPK (3%)
Postmarketing Reports
Myalgia, rhabdomyolysis, muscle spasms, arthralgia
Pancreatitis
Renal failure
Hepatitis, cirrhosis
Anemia
Severely depressed HDL levels
Warnings
Contraindications
Hypersensitivity
Severe renal impairment (including dialysis)
Active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities
Pre-existing gallbladder disease
Breastfeeding women
Cautions
Effect on coronary heart disease morbidity and mortality not established
Increases risk of myositis or myopathy, and has been associated with rhabdomyolysis; risk may increase when coadministered with statins
Higher doses or coadministration with statins associated with increased serum transaminases
May increase serum creatinine
May increase cholesterol excretion in bile, potentially leading to cholelithiasis
Coadministration with warfarin may increase anticoagulant effects resulting in PT/INR prolongation
Pancreatitis reported; may be a failure of efficacy with severe hypertriglyceridemia, a direct drug effect, or secondary effect via biliary stone or sludge formation
May decrease hemoglobin, hematocrit, and leukocytes
Thrombocytopenia and agranulocytosis reported
Acute hypersensitivity reactions (eg, Stevens-Johnson syndrome, toxic necrolysis) reported PE and DVT reported
Paradoxical decreases in HDL cholesterol reported
Pregnancy and lactation
Pregnancy category: C
Lactation: Contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Fibricor, Trilipix (fenofibric acid)
Mechanism of action
Fenofibric acid is the active metabolite of fenofibrate
Activates peroxisome proliferator activated receptor-alpha (PPAR-alpha); increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reduces Apo CIII production (lipoprotein lipase inhibitor)
Reduces TC, LDL-C, Apo B, TG, and VLDL; increases HDL-C, Apo AI, and Apo AII
Absorption
Bioavailability: 81% (Trilipix)
Peak Plasma Time: 4-5 hr (Trilipix); 2.5 hr (Fibricor)
Distribution
Time to steady-state: 8 days (Trilipix); 9 days (Fibricor)
Protein Bound: 99%
Metabolism
Primarily conjugated with glucuronic acid; a small amount is reduced at the carbonyl moiety to a benzhydrol metabolite which is, in turn, conjugated with glucuronic acid
Elimination
Half-life: 20 hr
Excretion: Primarily in urine as fenofibric acid and fenofibric acid glucuronide
Pharmacogenomics
Genotyping patients with atherogenic dyslipidemia might establish who will benefit most from therapy with fenofibric to increase HDL-C
