Gemfibrozil activates peroxisome proliferator-activated receptor alpha (PPAR-α), a nuclear receptor that regulates lipid metabolism. This activation:

1. Reduces Triglycerides: Enhances lipoprotein lipase activity, accelerating the breakdown of triglyceride-rich very-low-density lipoproteins (VLDL) and chylomicrons.
2. Modifies Cholesterol Profile:
   • Increases high-density lipoprotein (HDL) cholesterol by stimulating apolipoprotein A-I and A-II synthesis.
   • Shifts low-density lipoprotein (LDL) particles to larger, less atherogenic forms (Lippincott Textbook of Pharmacology).

1. Hypertriglyceridemia:
   • Management of severe hypertriglyceridemia (Fredrickson type IV/V) to prevent acute pancreatitis.
2. Mixed Dyslipidemia:
   • Adjunctive therapy in patients with combined elevations of triglycerides and LDL cholesterol, particularly when statins are contraindicated or ineffective (BNF).
3. Primary Prevention:
   • May reduce cardiovascular risk in select patients with type 2 diabetes and dyslipidemia (Lange Basic & Clinical Pharmacology).

• Adults:
  • Standard Dose: 600 mg twice daily, taken 30 minutes before morning and evening meals.
• Renal Impairment:
  • Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²).
  • Use with caution in moderate renal impairment (eGFR 30–60 mL/min/1.73m²).
• Administration:
  • Administer with water before meals to enhance absorption.
  • Avoid concurrent bile acid sequestrants (e.g., cholestyramine); separate doses by 2 hours.

• Common (≥1%):
  • Gastrointestinal disturbances (dyspepsia, abdominal pain, diarrhoea).
  • Headache, fatigue, or dizziness.
• Serious (Rare):
  • Myopathy/Rhabdomyolysis: Increased risk with concurrent statins.
  • Cholelithiasis: Due to increased biliary cholesterol excretion.
  • Hepatotoxicity: Discontinue if ALT/AST >3× upper limit of normal (ULN).

Pancreatitis: Linked to rapid triglyceride reduction

• Contraindications:
  • Severe hepatic or renal impairment.
  • Gallbladder disease, primary biliary cirrhosis.
  • Hypersensitivity to fibrates.
• Pregnancy/Lactation:
  • Avoid in pregnancy (Category C: potential fetal risk) and breastfeeding (excretion in milk unknown).
• Monitoring:
  • Baseline liver function tests (LFTs) and renal function: Repeat LFTs every 3–6 months.
  • Lipid Profile: Assess efficacy after 3 months.

Creatine Kinase (CK): Check if myalgia or muscle weakness occurs

1. Statins (e.g., simvastatin, atorvastatin): ↑ Risk of myopathy (avoid combination if possible).
2. Warfarin: Gemfibrozil ↑ anticoagulant effect (monitor INR closely).
3. CYP2C8/CYP2C9 Substrates (e.g., repaglinide, sulfonylureas): ↑ Drug levels (risk of hypoglycaemia).
4. Cyclosporine: ↑ Risk of nephrotoxicity.

• Generic Name: Gemfibrozil.
• Brand Names:
  • UK: Lopid.

US: Lopid, Jezil