l I P S I N (Fenofibrate)

• Fenofibrate is indicated for disorders of lipid metabolism that involve elevated triglyceride or cholesterol levels.
• Hypertriglyceridemia: lowers serum triglycerides, reduces very‑low‑density lipoprotein (VLDL) particles and helps prevent pancreatitis.
• Mixed dyslipidemia: decreases triglycerides, modestly raises high‑density lipoprotein (HDL) cholesterol and contributes to a more favorable total cholesterol/HDL ratio.
• Hypercholesterolemia (adjunct therapy): used together with statins to further lower low‑density lipoprotein (LDL) cholesterol when target levels are not met by statins alone.

• Fenofibrate activates peroxisome proliferator‑activated receptor‑alpha (PPARα), a nuclear transcription factor that regulates genes involved in lipid metabolism. Activation enhances β‑oxidation of fatty acids, increases lipoprotein lipase activity, and reduces hepatic synthesis of triglyceride‑rich lipoproteins, leading to decreased plasma triglycerides and modest increases in HDL cholesterol. It also lowers apolipoprotein C‑III expression, further facilitating triglyceride clearance. These combined actions improve the overall atherogenic lipid profile.

Fenofibrate may cause a range of adverse reactions, varying from mild to serious.

Common Side Effects

• Gastrointestinal discomfort: nausea, abdominal pain, dyspepsia or loss of appetite.
• Headache: mild to moderate intensity, often transient and responsive to simple analgesics.
• Elevated liver enzymes: transient increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels.
• Muscle pain: mild myalgia without weakness, usually self‑limiting.

Serious or Rare Side Effects

• Severe liver injury: jaundice, hepatitis, or hepatic failure requiring medical intervention.
• Rhabdomyolysis: rapid muscle breakdown with dark urine, markedly elevated creatine kinase and potential renal impairment.
• Allergic reactions: rash, pruritus, angioedema or anaphylaxis that may necessitate discontinuation.

When prescribing fenofibrate, clinicians should consider several precautionary measures to ensure safe use.

• Baseline liver function: assess ALT/AST before initiating therapy.
• Renal impairment: adjust use in patients with severe kidney disease.
• Drug interactions: review concomitant medications that affect lipid metabolism.
• Pregnancy and lactation: avoid use unless benefits outweigh potential risks.
• Muscle disorders: discontinue if unexplained muscle pain or weakness develops.
• Store at ambient temperature: keep below 25 °C, retain in original packaging and protect from moisture.

Fenofibrate can interact with other medicines, altering its efficacy or increasing toxicity.

Major Interactions (Avoid)

• Statins (especially high‑dose simvastatin): increased risk of myopathy and rhabdomyolysis.
• Cyclosporine: elevated fenofibrate plasma levels leading to hepatotoxicity.
• Gemfibrozil: additive risk of myopathy and rhabdomyolysis.

Moderate Interactions (Monitor Closely)

• Anticoagulants (warfarin): may enhance anticoagulant effect, requiring more frequent INR monitoring.
• Bile acid sequestrants (cholestyramine): reduce fenofibrate absorption, decreasing lipid‑lowering effect.
• Thiazide diuretics: may increase serum uric acid, raising gout risk.