FIBRICOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FIBRICOR (FIBRICOR).
FIBRICOR (fenofibrate) is a peroxisome proliferator-activated receptor alpha (PPARα) agonist. It increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase, and reduces production of apolipoprotein C-III (an inhibitor of lipoprotein lipase). This leads to decreased triglyceride and increased HDL cholesterol levels.
| Metabolism | Fenofibrate is a prodrug that is rapidly hydrolyzed by esterases to the active metabolite fenofibric acid. Fenofibric acid is primarily conjugated with glucuronic acid and excreted renally. Minor metabolism via CYP450 enzymes (CYP3A4). |
| Excretion | Approximately 60-70% of the dose is excreted renally as unchanged drug or glucuronide conjugate, and about 20-25% is excreted fecally. Biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 19-26 hours) in healthy volunteers, with clinical context indicating that steady state is achieved within 1 week of dosing. |
| Protein binding | Highly protein bound (>99%), primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.11-0.14 L/kg, indicating limited extravascular distribution with confinement primarily to plasma and interstitial fluid. |
| Bioavailability | Oral bioavailability is approximately 90% when taken with food; absorption is enhanced by food intake (compared to 65-70% in fasting state). |
| Onset of Action | Following oral administration, significant reduction in triglycerides is observed within 2-4 weeks, with maximal effects by 8-12 weeks. |
| Duration of Action | Duration of triglyceride-lowering effect persists for the dosing interval (once daily) when taken regularly. Effects may diminish over days to weeks after discontinuation. |
| Action Class | Class III Agents- anti arrhythmic |
FIBRICOR (fenofibric acid) is dosed as 45 mg or 135 mg orally once daily, with or without food. The typical adult dose is 135 mg daily. For mixed dyslipidemia, the recommended dose is 135 mg once daily; for severe hypertriglyceridemia, start with 45 to 135 mg once daily, titrating based on response.
| Dosage form | TABLET |
| Renal impairment | Mild to moderate renal impairment (eGFR 30-59 mL/min/1.73 m²): initial dose of 45 mg once daily, maximum dose 45 mg once daily. Severe renal impairment (eGFR <30 mL/min/1.73 m²): contraindicated. Hemodialysis: not recommended. |
| Liver impairment | Contraindicated in patients with active liver disease, including primary biliary cirrhosis, and in those with unexplained persistent liver function abnormalities. Child-Pugh Class A or B: contraindicated if preexisting liver disease. Child-Pugh Class C: contraindicated. No dose adjustment is defined; use is not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. Not recommended for use in patients <18 years. |
| Geriatric use | No specific dose adjustment required for age alone, but renal function (eGFR) should be assessed and dosing adjusted accordingly. Elderly patients are at higher risk for renal impairment; thus, the lowest effective dose should be used and renal function monitored. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FIBRICOR (FIBRICOR).
| Breastfeeding | Fenofibrate is excreted in rat milk but no human data on transfer or M/P ratio. Due to potential for serious adverse reactions in nursing infants, including interference with lipid metabolism, breastfeeding is not recommended during therapy. Consider discontinuing drug or abstaining from breastfeeding. |
| Teratogenic Risk | FIBRICOR (fenofibrate) is Pregnancy Category C. In animal studies, fenofibrate caused embryotoxicity and delayed ossification at doses 1-10 times the human exposure. There are no adequate human studies. Use during first trimester should be avoided due to theoretical risk of impaired cholesterol synthesis crucial for fetal development. Risk in second and third trimesters is unknown; however, fetal exposure may affect lipid metabolism. Use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
Warning: Hepatotoxicity. Fibrates have been associated with rare cases of severe hepatotoxicity, including liver failure. Serum transaminases should be monitored periodically. Discontinue if elevated levels persist.
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min)","Severe hepatic impairment (including primary biliary cirrhosis)","Pre-existing gallbladder disease","Nursing mothers (due to potential for adverse effects in infants)","Hypersensitivity to fenofibrate or any component"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests; discontinue if ALT >3x ULN or if symptoms persist","Myopathy/rhabdomyolysis: Risk increased with concomitant statins or in renal impairment","Renal impairment: Dose adjustment required for eGFR <30 mL/min; contraindicated in severe renal disease","Cholelithiasis: Increases biliary cholesterol secretion, raising risk of gallstones","Pancreatitis: Risk elevated in severe hypertriglyceridemia, particularly if TG >1000 mg/dL","Venous thromboembolism: Slight increase in risk reported"] |
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| Fetal Monitoring | Monitor maternal lipid profiles, liver function tests, and renal function periodically. Assess for signs of myopathy (CPK levels if muscle symptoms). Fetal monitoring includes standard prenatal care; no specific fetal tests required, but ultrasound may be considered if used during pregnancy. Monitor for potential gallstone formation. |
| Fertility Effects | In animal studies, fenofibrate caused reduced fertility and increased pre-implantation loss at high doses. Human data on fertility effects are lacking. Theoretically, may impair spermatogenesis or ovarian function due to hormonal modulation, but clinical significance unknown. |