fenofibrate
Brand: Tricor, Fenoglide
Prototype Drug
Drug Class: fibrate
Drug Family: antilipemic
Subclass: peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist
Organ Systems: cardiovascular
Mechanism of Action
PPAR-alpha agonist activating transcription of genes for lipoprotein lipase (LPL), apoA-I, apoA-II, and fatty acid oxidation enzymes; increases LPL activity, reduces triglycerides by 40-60%, raises HDL 10-20%.
PPAR-alpha (nuclear receptor)
Indications
- hypertriglyceridemia
- mixed dyslipidemia (high TG, low HDL)
- Fredrickson types IIb, III, IV, V
Contraindications
- severe renal impairment
- hepatic impairment
- pre-existing gallbladder disease
Adverse Effects
Common
- GI upset
- myalgia
- elevated serum creatinine (tubular secretion inhibition)
- elevated LFTs
Serious
- rhabdomyolysis (especially with statins — avoid gemfibrozil combination; fenofibrate safer)
- gallstones
- hepatotoxicity
Pharmacokinetics (ADME)
| Absorption | ~81% oral with food |
| Distribution | large Vd |
| Metabolism | prodrug to fenofibric acid by tissue esterases |
| Excretion | renal (fenofibric acid glucuronide) |
| Half-life | ~20 hours |
| Onset | 4-6 hours |
| Peak | 6-8 hours |
| Duration | 24 hours |
| Protein Binding | 99% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| statins | additive myopathy risk; safer than gemfibrozil but still monitor CK | moderate |
| warfarin | potentiates anticoagulant effect — reduce warfarin dose | major |
| cyclosporine | increased fenofibrate levels | moderate |
Nursing Considerations
- Take with food (improves absorption)
- Monitor LFTs at baseline and at 3 months
- Can be combined with statins (safer than gemfibrozil)
- Monitor renal function — fenofibrate raises serum creatinine
- ACCORD: fenofibrate + simvastatin did NOT reduce CV events vs simvastatin alone in T2DM
Clinical Pearls
- ACCORD-LIPID: combination fenofibrate + simvastatin did not reduce CV events over simvastatin alone
- Safer combination with statins than gemfibrozil (does not inhibit CYP2C8 or OATP1B1)
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.