Fibric Acid

Aka: Fibric Acid, Fibric Acid Derivative, Fibrate, Clofibrate

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II. Indications

  1. Hypertriglyceridemia

III. Contraindications

  1. Absolute
    1. Preexisting Gallstones
    2. Severe Hepatic or renal disease
      1. Monitor Serum Creatinine (baseline and every 6 months)
      2. Monitor Liver Function Tests (baseline and periodically)
  2. Relative
    1. Concurrent Statin due to Myopathy risk
      1. Exercise caution when using these together
      2. Tricor is commonly used with Statins (Gemfibrozil is higher risk)
    2. Concurrent Coumadin use
    3. Avoid as a single agent in Coronary Artery Disease

IV. Mechanism

  1. Activates nuclear transcription factor PPARa (peroxisome proliferator-activated receptor alpha)
    1. PPARa regulates genes controlling lipid and Glucose Metabolism
    2. PPARa also regulates controlling inflammation and endothelial function
  2. Mechanism in reduced Serum Triglyceride levels
    1. Inhibits VLDL synthesis
    2. Increases LipoproteinLipase activity

V. Medications

  1. Gemfibrozil (Lopid)
    1. Dose: 600 mg orally twice daily
  2. Fenofibrate (Tricor)
    1. Less likely to cause Rhabdomyolysis with Statin
  3. Fenofibric Acid (Trilipix)
    1. Rebranded version of Tricor in time for generic Fenofibrate release in 2011
  4. Clofibrate
    1. Discontinued in 2002
    2. Increased mortality from malignant and GI disease

VI. Efficacy

  1. Lipid effects
    1. Decreases Triglycerides (20-50%)
    2. Increases LDL Cholesterol (10-15%)
    3. Decreases VLDL Cholesterol
    4. Increases HDL Cholesterol (10-15%)
  2. Outcome effects
    1. No Fibrate has been shown to reduce all cause mortality
    2. Gemfibrozil is the only Fibrate shown to decrease cardiovascular events
      1. NNT to prevent one coronary event: 46-125

VII. Adverse Effects

  1. Gastrointestinal effects
    1. Gastrointestinal upset
    2. Abdominal Pain
    3. Appendicitis
    4. Cholecystitis (increased risk by 2-3%)
      1. Increases Cholesterol excretion into bile
  2. Miscellaneous
    1. Rash
    2. Renal dysfunction (rare)
    3. Myopathy (rare)
  3. Cardiovascular
    1. May decrease HDL Cholesterol (avoid in low HDL Cholesterol)

VIII. Drug Interactions

  1. Avoid in combination with agents that increase Myopathy and Rhabdomyolysis risk
    1. Statins
    2. Colchicine
  2. May potentiate effects of other medications
    1. Warfarin
    2. Oral Hypoglycemic Agents
  3. Bile Acid Sequestrants
    1. Take Fibrates 2 hours before or 4 hours after Bile Acid Sequestrants

IX. References

  1. (2022) Non-StatinLipid Lowering Agents, Presc Lett, #380202
  2. (2022) Med Lett Drug Ther 64(1659): 145-52
  3. Last (2011) Am Fam Physician 84(5): 551-8 [PubMed]
  4. Studer (2005) Arch Intern Med 165(7): 725-30 [PubMed]
  5. Sharma (2009) Ann Intern Med 151(9):622-30 [PubMed]

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