Back To Search Results

Fibrate Medications

Editor: Ricardo Correa Updated: 5/1/2023 7:23:39 PM


The fibrates are a type of amphipathic carboxylic acids belonging to the class of drugs used to lower serum cholesterol levels. They are currently the most important class of drugs combating the worldwide epidemic of atherogenic dyslipidemia. Statins help reduce the levels of low-density lipoprotein cholesterol (LDL) but do not exert much of an effect on serum triglyceride or HDL levels, where the use of fibrates is required. Research shows that the effects of different fibrate medications, while essentially being the same, differ slightly regarding their impact on glucose metabolism, insulin resistance, intermittent claudication, and microvascular effects of diabetes mellitus; this provides the option of tailoring therapy as per the needs of every patient.[1] The FDA approved indications of fibrates include :

  • For use as an adjunct to dietary modifications (restricted in saturated fats and cholesterol) in adults with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson type IIa and IIb). Fibrates help to reduce serum LDL, total cholesterol, triglycerides, apolipoprotein B (Apo-B) and increase high-density lipoprotein cholesterol (HDL).
  • To be used, an adjunct to dietary modifications in adults with severe hypertriglyceridemia (Fredrickson type IV and V).

A non-FDA-approved use of fibrates is primary biliary cholangitis.

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

Fibrates work by a combination of the following mechanisms to cause their hypotriglyceridemic effects[2]:

  • Reduce the availability of substrates to allow triglyceride synthesis in the liver.
  • Reverse cholesterol movement and stimulate cellular fatty acid uptake and modulate low-density lipoprotein (LDL) receptor and ligand interaction. Fibrates promote receptor-mediated clearance of LDL after stimulating its secretion, causing this catabolism to occur at a 20% greater rate compared to an untreated patient. This action results in an overall decrease in very-low-density lipoproteins (VLDL).
  • Small dense LDL, a fraction of LDL that produces the maximum peroxidation products, is reduced via the action of fibrates by activating lipoprotein lipase (LPL). Fibrates increase this LPL mediated lipolysis via activation of transcription factors for peroxisome proliferator-activated receptors (PPAR).[3]

Fibrates also work to increase high-density lipoprotein (HDL) levels by upregulating the production of Apo-AI and apo-AII in the liver.


Before starting fibrate therapy, patients should start on an adequate lipid-lowering diet. It should be used only as an adjunct to lipid-lowering diet and medication and not as a first-line mode of therapy. 

Fibrates are administered orally, ideally as once a day tablets. According to the FDA, the dosing of fibrates in adults is as follows, adjusted for the patient profile :

  • Primary hypercholesterolemia or mixed dyslipidemia - Start with 120 mg daily.
  • Severe hypertriglyceridemia - The dose ranges from 40 mg to 120 mg daily and is adjusted according to lipid levels.
  • Renally impaired patients - Initiate with 40 mg per day. Conduct regular renal function tests and serum cholesterol levels and up-titrate the drug as required.
  • Geriatric patients - The dosing is per the renal function of the patient.

The above regime is for fenofibrate, which is available as 40 mg and 120 mg tablets. The patient's response to it must be measured every 4 to 8 weeks, followed by adjusting the drug dosage.

Adverse Effects

 The following is a list of adverse effects of fibrates:

  • The most common adverse effects of this drug class include reporting of deranged AST, ALT levels, along with infrequent elevations in serum CPK (creatinine phosphokinase) levels during therapy.
  • Most likely, due to the effect mediated by PPAR-alpha, fibrates can reversibly increase serum creatinine and homocysteine levels. But clinical trials have failed to prove renal failure associated with this.
  • Patients can present with leg cramps, abdominal pain, etc., as fibrates can cause a slightly increased risk (less than 1.0%) of myopathy, cholelithiasis, and venous thrombosis.
  • Fibrates generally should be avoided in combination with statins since they can inhibit statin metabolism, causing an increased risk of myopathy. Recommendations are to always to measure serum creatinine levels and renal function before using the two drugs simultaneously. Gemfibrozil has proved to be unsafe for this interaction, whereas clinicians can still use bezafibrate and fenofibrate.
  • Discontinue fibrate therapy or reduce the fibrate dose if a clinically significant elevation of serum creatinine occurs in the patient, after excluding all possible causes for the same.[4]


The contra-indications to the use of fibrate therapy are:

  • Known hypersensitivity to the drug class.
  • Active liver disease, as fibrates are shown to be hepatotoxic if pre-existing liver inflammatory states exist.[5]
  • Active gall bladder disease as fibrates cause a PPAR-Alpha mediated downregulation in bile acid production, which, in turn, is responsible for an increased tendency to form gall stones.[6]
  • Severe renal dysfunction, including patients receiving dialysis therapy.


Fibrates are usually safe drugs that do not need routine monitoring except in the following cases:

  • Co-administration with statins increases the risk for myopathy. Monitor these patients for serum CPK levels, especially if they have diabetes, hypothyroidism, or renal failure.
  • Monitor renal function tests in patients with pre-existing deranged renal function.
  • Monitor serum transaminases since fibrates can sometimes elevate these levels.
  • Conduct gallbladder studies in patients with pre-existing gallbladder disease or if cholelithiasis is suspected.
  • Monitor PT/INR levels at least thrice a week when co-administering with coumarin anti-coagulants to prevent bleeding complications as fibrates are known to potentiate the effects of the former.[7]


  • There is no known antidote to fibrate toxicity. If possible, eliminate any unabsorbed drug via emesis or gastric lavage, maintaining the necessary common precautions for airway protection.
  • If a patient happens to overdose on fibrates, do not consider hemodialysis as fibrates are highly plasma protein-bound drugs.

Enhancing Healthcare Team Outcomes

Managing appropriate drug use requires free-flowing and efficient communication between the entire interprofessional healthcare team, including clinicians, mid-level practitioners, nurses, and pharmacists. The same applies to the use of fibrates. Health professionals should bear in mind the adverse outcome of fibrates regarding liver function tests (LFTs) and ensure that there is regular testing, especially if the patient has pre-existing liver disease. Fibrates are also notorious for causing drug interactions, and health professionals should be thorough with the patient's medication history before prescribing them. If a patient is already on statins, monitor carefully for the development of myopathies, evaluate clotting studies for those on anticoagulants, etc. Most importantly, it is the responsibility of healthcare providers to counsel the patients about the adverse effects of this drug and ensure they report any new or untoward symptoms(such as muscle cramps, abdominal pain, indigestion, etc.) after initiating the drug.

An interprofessional team effort is necessary to accomplish the above. The clinician will make the decision to initiate fibrate therapy based on the case facts before them. Still, they would do well to include a pharmacist who can review the patient's current medications to check for possible drug interactions and verify appropriate dosing. The pharmacist can also assist in choosing a specific fibrate depending on the patient's particular parameters. Nursing should be aware of the signs of the most common interactions and adverse effects; they can check on patient compliance and monitor for adverse events, alerting the prescriber when appropriate. In this way, fibrate therapy can achieve the best possible result with minimal chance of encountering adverse effects. [Level 5]



Tenenbaum A, Fisman EZ. Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovascular diabetology. 2012 Oct 11:11():125. doi: 10.1186/1475-2840-11-125. Epub 2012 Oct 11     [PubMed PMID: 23057687]


Shepherd J. Mechanism of action of fibrates. Postgraduate medical journal. 1993:69 Suppl 1():S34-41     [PubMed PMID: 8497455]


Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10:98(19):2088-93     [PubMed PMID: 9808609]


Davidson MH,Armani A,McKenney JM,Jacobson TA, Safety considerations with fibrate therapy. The American journal of cardiology. 2007 Mar 19;     [PubMed PMID: 17368275]


Škop V, Trnovská J, Oliyarnyk O, Marková I, Malínská H, Kazdová L, Zídek V, Landa V, Mlejnek P, Šimáková M, Kůdela M, Pravenec M, Šilhavý J. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein. Physiological research. 2016 Dec 13:65(6):891-899     [PubMed PMID: 27539098]


Post SM, Duez H, Gervois PP, Staels B, Kuipers F, Princen HM. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arteriosclerosis, thrombosis, and vascular biology. 2001 Nov:21(11):1840-5     [PubMed PMID: 11701475]

Level 3 (low-level) evidence


Ascah KJ, Rock GA, Wells PS. Interaction between fenofibrate and warfarin. The Annals of pharmacotherapy. 1998 Jul-Aug:32(7-8):765-8     [PubMed PMID: 9681093]

Level 3 (low-level) evidence