FENOFIBRATE (MICRONIZED)
Clinical safety rating: safe
Can potentiate the effects of warfarin increasing INR Can cause cholelithiasis and myopathy.
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 apoprotein C-III. It also increases apoproteins A-I and A-II, leading to increased HDL cholesterol.
| Metabolism | Primarily hepatic via glucuronidation; fenofibrate is a prodrug hydrolyzed by esterases to the active moiety fenofibric acid. Fenofibric acid is further metabolized by glucuronidation and excreted in urine. CYP450 enzymes are not significantly involved. |
| Excretion | Renal: 60% (as fenofibric acid and glucuronide conjugates); Fecal: 25%; Biliary: minor. |
| Half-life | Terminal half-life of fenofibric acid is approximately 20 hours (range 19–27 hours) in adults, allowing once-daily dosing. |
| Protein binding | Fenofibric acid: 99% bound, primarily to albumin. |
| Volume of Distribution | Apparent Vd: 0.9 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral (micronized): 66–81% under fed conditions; absorption increased by 35% with food. |
| Onset of Action | Oral: Reduction in triglycerides and LDL-C observed within 2–5 days; maximal effect achieved in 2–4 weeks. |
| Duration of Action | Lipid-lowering effects persist for 4–6 weeks after discontinuation due to slow elimination; clinical dosing interval is 24 hours. |
Fenofibrate (micronized) 145 mg orally once daily; alternatively 48 mg orally once daily to 145 mg orally once daily as tolerated.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-59 mL/min/1.73 m2: reduce dose; maximum 48 mg/day. eGFR <30 mL/min/1.73 m2: contraindicated. |
| Liver impairment | Child-Pugh class A: use with caution; reduce dose by 50%. Child-Pugh class B or C: contraindicated. |
| Pediatric use | Not approved in children; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; start at low end of dosing range due to potential renal impairment. |
| 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.
| FDA category | Animal |
| Breastfeeding | Excretion into human milk is unknown. The M/P ratio has not been determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued or fenofibrate avoided, especially if the infant has hypertriglyceridemia or other lipid disorders. |
| Teratogenic Risk | Fenofibrate is classified as FDA Pregnancy Category C. In animal studies, it caused embryotoxicity and teratogenicity at maternal toxic doses. Human data are limited. First trimester: Unknown risk, avoid unless clearly needed. Second and third trimesters: May cause fetal harm; use only if benefit outweighs risk, as it may interfere with fetal lipid metabolism and development. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Nausea |
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m²)","Active liver disease (including primary biliary cirrhosis) or unexplained persistent liver function abnormalities","Known gallbladder disease","Hypersensitivity to fenofibrate or any component of the formulation","Breastfeeding"]
| Precautions | ["Hepatotoxicity: increases in serum transaminases; monitor liver function","Cholelithiasis: increases cholesterol excretion into bile, risk of gallstones","Myopathy/rhabdomyolysis: risk increased with concomitant HMG-CoA reductase inhibitors (statins), especially in patients with renal impairment, diabetes, or hypothyroidism","Renal impairment: dose adjustment required; monitor renal function","Pancreatitis: reported in patients with severe hypertriglyceridemia"] |
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| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST), renal function (serum creatinine), and complete blood count periodically. Monitor fetal growth and well-being with ultrasound if used in pregnancy. Assess for maternal myopathy or rhabdomyolysis (report muscle pain, tenderness, weakness). |
| Fertility Effects | No specific human data on fertility impairment. Animal studies have not shown adverse effects on fertility. However, fenofibrate may affect spermatogenesis in males (reversible upon discontinuation). In females, potential disruption of hormonal balance due to lipid modulation could theoretically affect ovulation, but clinical significance is unknown. |