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Fibrates

Authoring team

drugs include:

  • ciprofibrate
  • gemfibrizil
  • bezafibrate
  • fenofibrate

actions:

  • main actions are to decrease serum triglyceride(via reduced hepatic production and increased triglyceride clearance by the peripheral tissues) and increase HDL
    • acts via activation of Peroxisome proliferator-activated receptor (PPAR) alpha - this is involved in regulation of a number of genes involved in lipid metabolism (e.g. those with encoding for Apo CIII, Apo AI, Apo AII and lipoprotein lipase)
    • LDL cholesterol and apo B levels may be reduced (depending on the fibrate and type of hyperlipidaemia e.g. may cause an increase in LDL cholesterol levels if used in patient with raised triglycerides and low LDL cholesterol levels at the onset of treatment)
    • fibrates are effective at reducing the circulating concentration of small, dense LDL
    • fibrate therapy also leads to improved postprandial triglyceride clearance
    • effects on lipid profile has been evaluated in a meta-analysis (1):
      • 11% reduction in total cholesterol
      • 36% reduction in triglycerides
      • 8% reduction in low-density lipoprotein cholesterol
      • 10% increase in high-density lipoprotein cholesterol
      • both fibrates and niacin were shown to be well-tolerated and safe. Fibrates reduced the risk for major coronary events by 25% (95% confidence interval 10% to 38%).
  • fibrates increase cholesterol excretion in bile - so predispose to formation of cholesterol gallstones
    • should be avoided in gallstone disease and may result in a paradoxical increase in cholesterol in patients with cholestatic liver disease

Cautions/Contraindications include:

  • caution - renal impairment - fibrates may cause increases in creatinine levels
  • contraindications - severe hepatic impairment, hypoalbuminaemia, primary biliary cirrhosis, gallbladder disease, nephrotic syndrome, pregnancy and breast-feeding

Fibrates may interact significantly with anticoagulant therapy e.g. warfarin.

Side effects include:

  • in general, side effects are mild - these include gastrointestinal disturbances and headache. Pruritus and rashes have been reported
  • mild elevations in muscle and hepatic enzymes may occur
  • increase in risk of bile-acid lithogenicity (fibrate treatment should be avoided in patients with known gallstones)

Any response to fibrates, as for statins, is evident by four weeks and continuation or change can be reviewed (2).

Note the concomitant use of cerivastatin and gemfibrozil is contraindicated (3).

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

  1. Birjmohun RS et al. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005;45:185-97.
  2. Prescriber 2000;11 (23): 77-85.
  3. Bayer plc (27th June 2001). Letter re: Gemfibrozil contraindication.

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