FENOFIBRIC ACID
Clinical safety rating
cautionComprehensive clinical and safety monograph for FENOFIBRIC ACID (FENOFIBRIC ACID).
Comprehensive clinical and safety monograph for FENOFIBRIC ACID (FENOFIBRIC ACID).
Adjunct to diet for treatment of severe hypertriglyceridemia (Fredrickson types IV and V hyperlipidemia)Adjunct to diet for reduction of LDL-C, total-C, triglycerides, and Apo B in primary hypercholesterolemia or mixed dyslipidemia (Fredrickson types IIa and IIb)
Fenofibric acid is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that increases lipolysis and clearance of triglyceride-rich lipoproteins and reduces apolipoprotein C-III production, leading to decreased triglycerides and increased HDL cholesterol.
| Metabolism | Primarily hepatic via glucuronidation; minor CYP3A4 involvement. Excreted as glucuronide conjugates in urine and feces. |
| Excretion | Primarily renal as unchanged drug and glucuronide conjugate (approximately 60-70% of dose); remainder eliminated via biliary/fecal routes (~25%). |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 15-25 h) for fenofibric acid, supporting once-daily dosing. In renal impairment, half-life may be prolonged. |
| Protein binding | Highly bound to serum albumin (approximately 99%). |
| Volume of Distribution | Approximately 0.4 L/kg (range 0.2-0.6 L/kg), indicating distribution mainly in extracellular fluid. |
| Bioavailability | Oral bioavailability of fenofibric acid is approximately 100% when administered as the choline salt; the capsule formulation has high bioavailability relative to tablet. Food may reduce rate but not extent of absorption. |
| Onset of Action | Therapeutic effects on serum lipids (triglyceride reduction) may be seen within 2-4 weeks of oral dosing; maximal effect by 8-12 weeks. |
| Duration of Action | Duration of action for lipid-lowering extends beyond 24 hours with once-daily administration, maintaining steady-state concentrations. Effects persist with continued therapy. |
| Molecular Weight | 360.47 |
135 mg orally once daily
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | If eGFR 30-59 mL/min: reduce dose to 45 mg orally once daily. If eGFR <30 mL/min: contraindicated. |
| Liver impairment | Contraindicated in Child-Pugh class B or C; no dose adjustment defined for Child-Pugh A (use with caution). |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment required; consider renal function and potential for decreased renal clearance in elderly. |
| 1st trimester | Avoid; insufficient data in pregnant women. Animal studies show fetotoxicity at doses similar to human exposure. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid; no adequate human studies. Potential fetal skeletal effects. Use only if clearly needed. |
| 3rd trimester | Avoid; may interfere with maternal lipid metabolism and fetal development. Not recommended during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for FENOFIBRIC ACID (FENOFIBRIC ACID).
| Placental transfer | Evidence of placental transfer in animal studies; limited human data. Likely crosses placenta due to molecular weight <500 Da. |
| Breastfeeding | Excreted into human milk at low concentrations. However, due to potential for adverse effects in nursing infants (e.g., lipid metabolism disruption), caution is advised. Consider alternative therapies or discontinue breastfeeding. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Data insufficient to assess risk; animal studies show embryotoxicity and teratogenicity at high doses. Second/third trimesters: Avoid use due to potential fetal harm; no well-controlled human studies. |
| Fetal Monitoring | Monitor maternal liver function, renal function, and lipid profiles. Monitor fetal growth and development via ultrasound if used during pregnancy. |
| Fertility Effects | Reversible fertility impairment reported in animal studies; human data limited. May affect spermatogenesis and ovulation. |
■ FDA Black Box Warning
None
| Serious Effects |
Severe renal impairment (eGFR <30 mL/min/1.73 m²)Active liver disease (including primary biliary cirrhosis)Preexisting gallbladder diseaseKnown hypersensitivity to fenofibric acid or any component of the formulation
| Precautions | Hepatotoxicity: elevation of serum transaminases; contraindicated in active liver disease., Myopathy/rhabdomyolysis risk, especially with statins or in patients with renal impairment, hypothyroidism, or alcohol abuse., Cholelithiasis: risk of gallstones due to increased cholesterol excretion into bile., Pancreatitis: reported in hypertriglyceridemia patients., Renal impairment: dose adjustment required; avoid in severe renal disease., Venothromboembolic events: increased risk in clinical trials. |
| Food/Dietary | Take with food to enhance absorption and reduce gastrointestinal intolerance. Avoid high-fat meals as they may exacerbate hypertriglyceridemia and reduce drug efficacy. |
| Clinical Pearls | Fenofibric acid is a PPARα agonist that reduces triglycerides by 30-50% and increases HDL; monitor renal function as dose adjustment required for CrCl 30-59 mL/min; contraindicated in severe renal impairment (CrCl <30 mL/min) and active liver disease; may increase serum creatinine; use with caution in patients with gallbladder disease; can potentiate warfarin effect (monitor INR). |
| Patient Advice | Take with food to reduce GI side effects. · Report unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise. · Avoid alcohol as it can increase triglyceride levels and worsen liver effects. · This medication is not a substitute for diet and exercise; continue lifestyle modifications. · Notify your doctor if you develop abdominal pain (possible gallstones). |
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