FENOFIBRATE
Clinical safety rating: safe
Animal studies have demonstrated safety
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 reducing production of apolipoprotein C-III.
| Metabolism | Fenofibrate is metabolized primarily by glucuronidation and to a lesser extent by CYP450 enzymes (CYP3A4). The major active metabolite is fenofibric acid. |
| Excretion | Renal: approximately 60% of the dose as fenofibric acid glucuronide; unchanged fenofibric acid < 10%. Biliary/fecal: approximately 25% as fenofibric acid and conjugates. Renal excretion is predominant. |
| Half-life | Terminal elimination half-life of fenofibric acid is approximately 20 hours (range 16-25 hours), allowing once-daily dosing. Steady-state is reached within 5 days. |
| Protein binding | Fenofibric acid is extensively bound to albumin, with binding > 99%. |
| Volume of Distribution | Apparent volume of distribution is approximately 0.9 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: Absolute bioavailability of fenofibric acid from fenofibrate capsules is approximately 60-90% due to first-pass metabolism. Food enhances absorption; bioavailability is increased by approximately 30% when taken with meals. |
| Onset of Action | Oral: Reduction in serum triglycerides may be observed within 2-5 days; maximal effect on triglycerides and LDL-C is seen after 4-8 weeks of continuous therapy. |
| Duration of Action | Duration of lipid-lowering effect persists for the dosing interval (24 hours) with once-daily dosing. After discontinuation, lipid levels return to baseline within several weeks. |
Fenofibrate: 48-145 mg orally once daily. For fenofibric acid: 45-135 mg orally once daily. Capsules should be taken with meals.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: reduce dose by 50% (e.g., fenofibrate 48 mg or fenofibric acid 45 mg once daily). eGFR <30 mL/min: contraindicated. Use not recommended in dialysis. |
| Liver impairment | Contraindicated in Child-Pugh class B and C cirrhosis. For mild hepatic impairment (Child-Pugh A): no specific dose adjustment recommended, but use with caution. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required based on age alone. However, renal function should be monitored closely due to age-related decline; adjust dose based on eGFR per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Can potentiate the effects of warfarin increasing INR Can cause cholelithiasis and myopathy.
| Breastfeeding | Excretion into human milk is unknown; however, fenofibrate is highly protein-bound and lipid-soluble, potentially present in milk. M/P ratio not established. Breastfeeding is not recommended due to risk of adverse effects in the infant. Alternative agents preferred. |
| Teratogenic Risk | Fenofibrate is contraindicated in pregnancy (FDA Category C). Animal studies show fetal toxicity at maternal toxic doses. Human data are insufficient; however, due to its mechanism (PPARα agonist) and potential for fetal harm, use is not recommended. First trimester: potential teratogenic effects unknown but caution. Second and third trimesters: may cause fetal growth restriction or other adverse effects. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Nausea |
| Serious Effects |
["Severe renal impairment (CrCl < 30 mL/min)","Active liver disease, including those with unexplained persistent liver function abnormalities","Preexisting gallbladder disease","Nursing mothers","Known hypersensitivity to fenofibrate or fenofibric acid"]
| Precautions | ["Hepatotoxicity: elevations in serum transaminases; monitoring recommended","Cholelithiasis: increased cholesterol excretion into bile may cause gallstones","Pancreatitis: associated with triglyceride reduction; however, acute pancreatitis may occur","Myopathy/rhabdomyolysis: risk increased with concomitant HMG-CoA reductase inhibitors (statins), especially in patients with renal impairment","Renal impairment: dose adjustment required (CrCl < 30 mL/min contraindicated; use lower dose for CrCl 30-59 mL/min)","Venous thromboembolic disease: observed in clinical trials"] |
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| Fetal Monitoring | Monitor maternal liver function tests (LFTs), renal function (serum creatinine), and lipid panel. Fetal monitoring: ultrasound for growth assessment if exposure occurs during pregnancy. No specific fetal heart rate monitoring required unless other indications. |
| Fertility Effects | Effects on fertility in humans are unknown. In animal studies, fenofibrate did not impair fertility at relevant doses. However, as a PPARα agonist, it may theoretically affect reproductive hormone synthesis; clinical significance unclear. |