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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Related Studies

Ontology: Clofibrate (C0009002)

Definition (NCI) An aryloxyisobutyric acid derivate with antihyperlipidemic activity. Although the exact mechanism of action has not been fully characterized, clofibrate may enhance the conversion of very-low-density lipoprotein (VLDL) to low-density lipoprotein (LDL), decreasing the production of hepatic VLDL, inhibiting cholesterol production, and increasing fecal excretion of neutral sterols.
Definition (MSH) A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
Definition (CSP) fibric acid derivative used in the treatment of hyperlipoproteinemia and hypertriglyceridemia.
Definition (PDQ) An aryloxyisobutyric acid derivate with antihyperlipidemic activity. Although the exact mechanism of action has not been fully characterized, clofibrate may enhance the conversion of very-low-density lipoprotein (VLDL) to low-density lipoprotein (LDL), decreasing the production of hepatic VLDL, inhibiting cholesterol production, and increasing fecal excretion of neutral sterols. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42108&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42108&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C378" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002994
SnomedCT 387439004, 77035009
LNC LP16082-7, MTHU016298
English clofibrate, Chlorophenoxyisobutyrate, Ethyl, Ethyl Chlorophenoxyisobutyrate, Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-, ethyl ester, 2-(4-Chlorophenoxy)-2-methylpropanoic acid ethyl ester, Ethyl 2-(4-Chlorophenoxy)-2-methylpropanoate, Ethyl p-Chlorophenoxyisobyturate, Clofibrate, CFB, clofibrate (medication), Clofibrate [Chemical/Ingredient], clofibrates, Clofibric Acid, Ethyl Ester, Clofibrate (product), Clofibrate (substance), CLOFIBRATE
Swedish Klofibrat
Czech klofibrát
Finnish Klofibraatti
Russian KLOFIBRAT, КЛОФИБРАТ
Italian Etil clorofenossi isobutirrato, Clofibrato
Croatian KLOFIBRAT
Polish Klofibrat
Japanese クロフィブレート, クロフィブラート
Spanish clofibrato (producto), clofibrato (sustancia), clofibrato, Clofibrato
French Clofibrate
German Clofibrat
Portuguese Clofibrato
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Fibrates (C1449704)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH D058607
English Fibrates
French Fibrates
German Fibrate
Czech fibráty
Spanish Fibratos
Portuguese Fibratos
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Fibric Acids (C2936462)

Definition (MSH) Compounds that either share the structure of fibric acid in their molecular arrangement or are considered variants of the fibric acid structure.
Concepts Organic Chemical (T109)
MSH D058607
English 2 Phenoxy Isobutyric Acids, 2-Phenoxy-2-Methylpropionic Acid Derivatives, Methyl 2 Phenoxypropanoic Acid Derivatives, Fibric Acid Derivatives, Acid Derivatives, Fibric, Fibric Acids, Methyl-2-Phenoxypropanoic Acid Derivatives, Isobutyric Acids, 2-Phenoxy, 2-Phenoxy Isobutyric Acids, 2 Phenoxy 2 Methylpropionic Acid Derivatives, Fibric Acids [Chemical/Ingredient]
French Dérivés de l'acide fibrique, Acides fibriques
German Fibrische Saeuren, Fibrische Säurederivate, Fibric Saeure-Derivate, Fibric Saeurederivate, Fibric Säurederivate, Fibrische Saeure-Derivate, Fibrische Säuren, Fibric Säure-Derivate, Fibrische Säure-Derivate, Fibrische Saeurederivate
Czech kyselina fibrová - deriváty
Italian Acidi fibrici
Spanish Ácidos Fíbricos
Russian ФИБРОЕВЫЕ КИСЛОТЫ, ФИБРАТЫ, ФИБРОЕВОЙ КИСЛОТЫ ПРОИЗВОДНЫЕ, ФИБРОЕВОЙ КИСЛОТЫ СОЛИ, FIBROEVOI KISLOTY SOLI, FIBROEVYE KISLOTY, FIBRATY, FIBROEVOI KISLOTY PROIZVODNYE
Portuguese Ácidos Fíbricos
Croatian Not Translated[Fibric Acids]
Polish Kwasy fibrynowe
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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