FENOFIBRIC ACID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FENOFIBRIC ACID (FENOFIBRIC ACID).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FENOFIBRIC ACID (FENOFIBRIC ACID).
| Breastfeeding | Excreted in breast milk in rats; human data unknown. Use caution, especially in preterm or jaundiced infants. M/P ratio not established. |
| 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 |
■ FDA Black Box Warning
None
| Serious Effects |
["Active liver disease including primary biliary cirrhosis and unexplained persistent liver function abnormalities.","Known gallbladder disease (cholelithiasis).","Severe renal impairment (eGFR <30 mL/min/1.73 m²).","Hypersensitivity to fenofibrate or fenofibric acid."]
| 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. |
Loading safety data…
| 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. |
| 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). |