Fenofibrate | Pharmacology Mentor

Generic Name

Fenofibrate

Peroxisome proliferator‑activated receptor‑α (PPAR‑α) agonist: activates nuclear transcription factors that up‑regulate genes for fatty acid β‑oxidation and apolipoprotein synthesis.
Increases lipoprotein lipase activity → enhanced catabolism of VLDL and chylomicrons.
Reduces hepatic triglyceride synthesis by inhibiting fatty acid synthase and acetyl‑CoA carboxylase.
Modestly up‑regulates HDL‑cholesterol by increasing apoA‑I production and enhancing reverse cholesterol transport.

> Result: ↓ plasma triglycerides (50–70 %), ↑ HDL‑C (10–25 %), ↓ LDL‑C (10–20 %) in mixed dyslipidemia.

Absorption: Rapid & nearly complete (≈95 %) after a 100 mg dose. Food increases early Cmax by ~30 % but does not alter overall exposure.
Distribution: Protein‑bound ~95 % (primarily to albumin and lipoproteins). Large volume of distribution (~1 L/kg).
Metabolism: Primarily hepatic via esterases → fenofibric acid, the active metabolite. Minor CYP450 involvement (CYP2C8 ~15 %).
Elimination: Renal excretion of fenofibric acid unchanged (~30 %) and via biliary route (~45 %). Half‑life of fenofibric acid ≈8–9 h; overall drug elimination ≈13 h.
Drug interactions: Limited CYP inhibition; caution with medications requiring hepatic metabolism. Concomitant use with statins may increase myopathy risk; with probenecid or cimetidine may elevate serum levels.

Hypertriglyceridemia (≥500 mg/dL) to reduce pancreatitis risk.
Mixed dyslipidemia: hypertriglyceridemia with low HDL‑C when statins are insufficient or contraindicated.
Familial combined hyperlipidemia (when a non‑statin approach is needed).
Metabolic syndrome–associated dyslipidemia as adjunctive therapy.

> Off‑label: used sometimes for severe hyperlipidemia where statins are poorly tolerated.

Contraindications:
Severe hepatic impairment (ALT/AST >3× ULN).
History of gallstones or biliary disease.
Known hypersensitivity to fibrates or constituents.
Pregnancy and lactation (Category X; avoid).
Warnings:
Liver injury: monitor liver enzymes; discontinue if rise >3× ULN.
Gallstone disease: may precipitate cholelithiasis.
Renal impairment: dose adjustment; caution in CrCl <30 mL/min.
Myopathy: rare, but risk heightened when combined with statins or high‑dose niacin.
Fluid‑shift: may transiently worsen edema or ascites.

Population	Initial Dose	Maintenance Dose	Administration Notes
Adults (general)	L 160 mg/10 mL solution (or 100 mg tablet)	1 L 160 mg/10 mL daily or 2×100 mg tablets	Take with food; 7–14 days to reach steady state.
Adults >70 y or renal impairment	Start 1/2 dose (80 mg tablet)	Titrate to 100 mg daily	Monitor renal & hepatic labs.
Pediatric (≥10 y, weight ≥35 kg)	5 mg/kg/day (max 100 mg)	As above	Same food instructions.
Pregnancy	Avoid	–	Not recommended.

> Titration: Adjust based on lipid panels and tolerance; maximal dose 2×100 mg/day.

Common (≥10 %): ↑ liver enzymes, muscle soreness, nausea, headache, dyspepsia.
Serious (≤1 %): rhabdomyolysis (esp. with statins), severe hepatotoxicity, gallstone formation, hypersensitivity dermatitis, interstitial nephritis.

> Risk‑stratified: patients with renal dysfunction, concomitant statin therapy, or advanced age require closer monitoring.

Parameter	Frequency	Rationale
Liver enzymes (ALT/AST)	Baseline; every 4–6 weeks for 6 months; then every 6–12 months	Detect hepatotoxicity early.
CK (Creatine Kinase)	Baseline; every 4–6 weeks if on statin, or if myalgias	Identify muscle injury.
Serum creatinine & eGFR	Baseline; every 3–6 months	Adjust dose in renal impairment.
Lipid profile (TG, HDL‑C, LDL‑C)	Every 12 weeks until target reached; then 6–12 months	Evaluate efficacy.
Gastro‑intestinal symptoms	At each visit	Detect bile‑stasis, gallbladder disease.

Fast Track in Pancreatitis Prevention: In patients with TG > 500 mg/dL, fenofibrate reduces pancreatitis risk by ~60 % when combined with lifestyle changes.
Statin Fibrates Combo: Combine only when LDL‑C still high; use low‑dose statin (10 mg) to minimize myopathy.
Renal Dosing: While fenofibrate is renally excreted, reduction in dose is usually not required for mild–moderate CKD (CrCl > 30 mL/min); for CrCl Take‑home point: Fenofibrate is most effective for triglyceride‑centric dyslipidemia, especially when combined with modest statin therapy or as an alternative in statin‑intolerant patients. Careful monitoring safeguards against rare but serious hepatic, renal, or musculoskeletal complications.