Gemfibrozil

• Hyperlipidemia (Type III)
• Hypertriglyceridemia (Type IV): Gemfibrozil, though not as effective as niacin (nicotinic acid, a form of Vitamin B3), is better tolerated.
• Reduce triglyceride levels [7]
• Reduce very low density lipoprotein (VLDL) levels
• Modest reduction of low density lipoprotein (LDL) levels
• Moderate increase in high density lipoprotein (HDL) levels

• GI distress
• Musculoskeletal pain
• Increased incidence of gallstone
• Hypokalemia (low blood potassium)
• Increased risk of cancer

• Gemfibrozil should not be given to these patients:
  • Hepatic dysfunction
• Gemfibrozil should be used with caution in these higher risk categories:
  • Biliary tract disease
  • Renal dysfunction
  • Pregnant women
  • Obese patients

• Anticoagulants: Gemfibrozil potentiates the action of warfarin and indanedione anticoagulants.
• Statin drugs: Concomitant administration of fibrates (including gemfibrozil) with statin drugs increases the risk of muscle cramping, myopathy, and rhabdomyolysis.[8]
• Gemfibrozil inhibits the activation of the liver's Cytochrome P450 system and CYP2C8, reducing hepatic metabolism of many drugs, and prolonging their half lives and duration of action.
  • Drugs metabolized by the Cytochrome P450 system include:
    • Many antidepressants
    • Many antipsychotics
    • Many antiepileptics
    • Theophylline and other methylxanthine drugs
    • Several anesthetic agents
    • Oral contraceptive pills
    • Statins
    • Warfarin
    • Selexipag

The exact mechanism of action of gemfibrozil is unknown; however, several theories exist regarding the very low density lipoprotein (VLDL) effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels and increase HDL-cholesterol; the mechanism behind HDL elevation is currently unknown.

Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating peroxisome proliferator-activated receptor alpha (PPARα) 'transcription factor ligand', a receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL.[9]

Gemfibrozil was selected from a series of related compounds synthesized in the laboratories of the American company Parke-Davis in the late 1970s. It came from research for compounds that lower plasma lipid levels in humans and in animals.[10]

Gemfibrozil has been detected in biosolids (the solids remaining after sewage treatment) at concentrations up to 2650 ng/g wet weight.[11] This indicates that it survives the wastewater treatment process. It is also detected as environmental persistent micropollutant in aquifers and in groundwaters in karstic areas.[12]

• "Gemfibrozil". Drug Information Portal. U.S. National Library of Medicine.
• "Lopid International Study" (PDF). European Medicines Agency. Archived from the original (PDF) on 2007-06-11.
• "Indian Health Service National Pharmacy and Therapeutics Committee Review of Statins, Fibrates, and Niacin" (PDF). Indian Health Service. San Diego: U.S. Department of Health and Human Services. February 12–13, 2009. Archived from the original (PDF) on June 22, 2014.