Fenofibrate

Fenofibrate is mainly used for primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate may slow the progression of diabetic retinopathy and the need for invasive treatment such as laser therapy in patients with type 2 diabetes with pre-existing retinopathy.{{cite journal | vauthors = Wong TY, Simó R, Mitchell P | title = Fenofibrate - a potential systemic treatment for diabetic retinopathy? | journal = American Journal of Ophthalmology | volume = 154 | issue = 1 | pages = 6–12 | date = July 2012 | pmid = 22709833 | doi = 10.1016/j.ajo.2012.03.013 }}{{cite journal | vauthors = Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, Merrifield A, Laatikainen LT, d'Emden MC, Crimet DC, O'Connell RL, Colman PG | title = Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial | language = English | journal = Lancet | volume = 370 | issue = 9600 | pages = 1687–1697 | date = November 2007 | pmid = 17988728 | doi = 10.1016/S0140-6736(07)61607-9 | s2cid = 30479730 }}{{cite journal | vauthors = Chew EY, Davis MD, Danis RP, Lovato JF, Perdue LH, Greven C, Genuth S, Goff DC, Leiter LA, Ismail-Beigi F, Ambrosius WT | title = The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study | language = English | journal = Ophthalmology | volume = 121 | issue = 12 | pages = 2443–2451 | date = December 2014 | pmid = 25172198 | pmc = 4252767 | doi = 10.1016/j.ophtha.2014.07.019 }} It was initially indicated for diabetic retinopathy in patients with type 2 diabetes and diabetic retinopathy in Australia.{{cite web|title=Australian Public Assessment Report for fenofibrate|url=https://www.tga.gov.au/file/6794/download|website=TGA|access-date=27 June 2015|archive-date=29 June 2015|archive-url=https://web.archive.org/web/20150629223527/https://www.tga.gov.au/file/6794/download|url-status=dead}} The large scale, international FIELD and ACCORD-Eye trials found that fenofibrate therapy reduced required laser treatment for diabetic retinopathy by 1.5% over 5 years, as well as reducing progression by 3.7% over 4 years. {{cite journal | vauthors = Fazio S | title = More clinical lessons from the FIELD study | journal = Cardiovascular Drugs and Therapy | volume = 23 | issue = 3 | pages = 235–241 | date = June 2009 | pmid = 19160032 | doi = 10.1007/s10557-008-6160-5 | s2cid = 7987660 }} Further studies looking at the role of fenofibrate in the progression of diabetic retinopathy as the primary outcome is warranted to understand its role in this condition. Although no statistically significant cardiovascular risk benefits were identified in these trials, benefits may accrue to add on therapy to patients with high triglyceride dyslipidaemia currently taking statin medications.{{cite journal | vauthors = Elam MB, Ginsberg HN, Lovato LC, Corson M, Largay J, Leiter LA, Lopez C, O'Connor PJ, Sweeney ME, Weiss D, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm R, Ismail-Beigi F, Goff DC, Fleg JL, Rosenberg Y, Byington RP | title = Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes | journal = JAMA Cardiology | volume = 2 | issue = 4 | pages = 370–380 | date = April 2017 | pmid = 28030716 | pmc = 5470410 | doi = 10.1001/jamacardio.2016.4828 }}{{cite journal | vauthors = Kim NH, Han KH, Choi J, Lee J, Kim SG | title = Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity matched cohort study | journal = BMJ | volume = 366 | pages = l5125 | date = September 2019 | pmid = 31562117 | pmc = 6763755 | doi = 10.1136/bmj.l5125 }}

Fenofibrate appears to reduce the risk of below ankle amputations in patients with Type 2 diabetes without microvascular disease.{{cite journal | vauthors = Rajamani K, Colman PG, Li LP, Best JD, Voysey M, D'Emden MC, Laakso M, Baker JR, Keech AC | title = Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial | journal = Lancet | volume = 373 | issue = 9677 | pages = 1780–1788 | date = May 2009 | pmid = 19465233 | pmc = 2687887 | doi = 10.1016/S0140-6736(09)60698-X }} The FIELD study reported that fenofibrate at doses of 200 mg daily, reduced the risk for any amputation by 37% independent of glycaemic control, presence or absence of dyslipidaemia and its lipid-lowering mechanism of action.{{cite journal | vauthors = Steiner G | title = How can we improve the management of vascular risk in type 2 diabetes: insights from FIELD | journal = Cardiovascular Drugs and Therapy | volume = 23 | issue = 5 | pages = 403–408 | date = October 2009 | pmid = 19757004 | doi = 10.1007/s10557-009-6190-7 | s2cid = 12747599 }} However, the cohort of participants who underwent amputations were more likely to have had previous cardiovascular disease (e.g. angina, myocardial infarction), longer duration of diabetes and had baseline neuropathy.

Fenofibrate has an off-label use as an added therapy of high blood uric acid levels in people who have gout.{{cite journal | vauthors = Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Pillinger MH, Merill J, Lee S, Prakash S, Kaldas M, Gogia M, Perez-Ruiz F, Taylor W, Lioté F, Choi H, Singh JA, Dalbeth N, Kaplan S, Niyyar V, Jones D, Yarows SA, Roessler B, Kerr G, King C, Levy G, Furst DE, Edwards NL, Mandell B, Schumacher HR, Robbins M, Wenger N, Terkeltaub R | title = 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia | journal = Arthritis Care & Research | volume = 64 | issue = 10 | pages = 1431–1446 | date = October 2012 | pmid = 23024028 | pmc = 3683400 | doi = 10.1002/acr.21772 }}

It is used in addition to diet to reduce elevated low-density lipoprotein cholesterol (LDL), total cholesterol, triglycerides (TG), and apolipoprotein B (apo B), and to increase high-density lipoprotein cholesterol (HDL) in adults with primary hypercholesterolemia or mixed dyslipidemia.

It is used in tandem with diet for treatment of adults with severe hypertriglyceridemia. Improving glycemic control in diabetics showing fasting chylomicronemia usually reduces the need for pharmacologic intervention.

Statins remain the first line for treatment of blood cholesterol. AHA guidelines from 2013 did not find evidence for routine use of additional medications.{{cite journal | vauthors = Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC, Tomaselli GF | title = 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines | journal = Circulation | volume = 129 | issue = 25 Suppl 2 | pages = S1-45 | date = June 2014 | pmid = 24222016 | doi = 10.1161/01.cir.0000437738.63853.7a | doi-access = free }}

Additionally, in 2016, the FDA filed "Withdrawal of Approval of Indications Related to the Coadministration With Statins in Applications for Niacin Extended-Release Tablets and Fenofibric Acid Delayed Release Capsules" noting "the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events. Consistent with this conclusion, FDA has determined that the benefits of niacin ER tablets and fenofibric acid DR capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn."{{cite web | title = AbbVie Inc. et al; Withdrawal of Approval of Indications Related to the Coadministration With Statins in Applications for Niacin Extended-Release Tablets and Fenofibric Acid Delayed- Release Capsules | url = https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-08887.pdf | work = Food and Drug Administration | date = 18 April 2016 }}

Fenofibrate is contraindicated in:

• Patients with severe renal impairment, including those receiving dialysis (2.7-fold increase in exposure, and increased accumulation during chronic dosing in patients with estimated glomerular filtration rate < 30 mL/min)
• Patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function test abnormalities
• Patients with preexisting gallbladder disease
• Nursing mothers
• Hypothyroidism
• Patients with known hypersensitivity to fenofibrate or fenofibric acid

The most common adverse events (>3% of patients with coadministered statins) are

{{div col|colwidth=25em}}

• Headache
• Back pain
• Nasopharyngitis
• Nausea
• Myalgia
• Joint pain or arthralgia
• Diarrhea
• Upper respiratory tract infection
• Calculi (Kidney Stones)

{{div col end}}

When fenofibrate and a statin are given as combination therapy, it is recommended that fenofibrate be given in the morning and the statin at night, so that the peak dosages do not overlap.{{cite journal | vauthors = Wierzbicki AS, Mikhailidis DP, Wray R, Schacter M, Cramb R, Simpson WG, Byrne CB | title = Statin-fibrate combination: therapy for hyperlipidemia: a review | journal = Current Medical Research and Opinion | volume = 19 | issue = 3 | pages = 155–168 | year = 2003 | pmid = 12814127 | doi = 10.1185/030079903125001668 | s2cid = 35948128 }}

Musculoskeletal

• Myopathy and rhabdomyolysis; increased risk when coadminstered with a statin, particularly in the elderly and patients with diabetes, kidney failure, hypothyroidismFenofibric Acid FDA Label Prescribing Information{{cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201573Orig1s000lbl.pdf|publisher=FDA|title=FDA Label Information}}

Hepatotoxicity

• Can increase serum transaminases; liver tests should be monitored periodically

Nephrotoxicity

• Can increase serum creatinine levels; renal function should be monitored periodically in patients with chronic kidney disease

Biliary

• Can increase cholesterol excretion into the bile, leading to risk of cholelithiasis; if suspected, gallbladder studies are indicated. See "Interaction" section under Bile acid sequestrant

Coagulation/Bleeding

• Exercise caution in concomitant treatment with oral Coumadin anticoagulants (e.g. warfarin). Adjust the dosage of Coumadin to maintain the prothrombin time/INR at desired level to prevent bleeding complications.

"There is no specific treatment for overdose with fenofibric acid delayed-release capsules. General supportive care is indicated, including monitoring of vital signs and observation of clinical status". Additionally, hemodialysis should not be considered as an overdose treatment option because fenofibrate heavily binds to plasma proteins and does not dialyze well.

These drug interactions with fenofibrate are considered major and may need therapy modifications:

• Bile acid sequestrants (e.g. cholestyramine, colestipol, etc.): If taken together, bile acid resins may bind to fenofibrate, resulting in a decrease in fenofibrate absorption. To maximize absorption, patients need to separate administration by at least 1 h before or 4 h to 6 h after taking the bile acid sequestrant.Product Information: TriCor(TM), fenofibrate. Abbott Laboratories, North Chicago, IL, 1998.
• Immunosuppressants (e.g. ciclosporin or tacrolimus): An increased risk of renal dysfunction exists with concomitant use of immunosuppressants and fenofibrate. Approach with caution when coadministering additional medications that decrease renal function.Product Information: Sandimmune(R) oral capsules, oral solution, intravenous injection, cyclosporine oral capsules, oral solution, intravenous injection. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2010.
• Vitamin K antagonists (e.g. warfarin): As previously mentioned, fenofibrate interacts with coumadin anticoagulants to increase the risk of bleeding. Dosage adjustment of vitamin K antagonist may be necessary.
• Statins: Combination of statins and fenofibrate may increase the risk of rhabdomyolysis or myopathy.Product Information: TRICOR(R) oral tablets, fenofibrate oral tablets. Abbott Laboratories, North Chicago, IL, 2007.

"In summary, enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression."

Fenofibrate is a fibrate derivative, a prodrug comprising fenofibric acid linked to an isopropyl ester. It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα). PPARα activates lipoprotein lipase and reduces apoprotein CIII, which increases lipolysis and elimination of triglyceride-rich particles from plasma.{{cite journal | vauthors = Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC | title = Mechanism of action of fibrates on lipid and lipoprotein metabolism | journal = Circulation | volume = 98 | issue = 19 | pages = 2088–2093 | date = November 1998 | pmid = 9808609 | doi = 10.1161/01.cir.98.19.2088 | citeseerx = 10.1.1.1004.321 | s2cid = 5858864 }}

PPARα also increases apoproteins AI and AII, reduces VLDL- and LDL-containing apoprotein B, and increases HDL-containing apoprotein AI and AII.

Fenofibrate is available in several formulations and is sold under several brand names. The formulations may differ in terms of pharmacokinetic properties, particularly bioavailability; some must be taken with meals, whereas others may be taken without regard to food.{{cite journal | vauthors = Ling H, Luoma JT, Hilleman D | title = A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations | journal = Cardiology Research | volume = 4 | issue = 2 | pages = 47–55 | date = April 2013 | pmid = 28352420 | pmc = 5358213 | doi = 10.4021/cr270w }}

The choline salt of fenofibrate is available in the United States, sold as Trilipix, and may be taken without regard to meals.{{cite journal | vauthors = Alagona P | title = Fenofibric acid: a new fibrate approved for use in combination with statin for the treatment of mixed dyslipidemia | journal = Vascular Health and Risk Management | volume = 6 | pages = 351–362 | date = May 2010 | pmid = 20531954 | pmc = 2879297 | doi = 10.2147/vhrm.s6714 | doi-access = free }}

Fenofibric acid was one of the 12 compounds identified in sludge samples taken from 12 wastewater treatment plants in California that were associated with estrogenic activity in in vitro.{{cite journal | vauthors = Black GP, He G, Denison MS, Young TM | title = Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge | journal = Environmental Science & Technology | volume = 55 | issue = 10 | pages = 6729–6739 | date = May 2021 | pmid = 33909413 | pmc = 8378343 | doi = 10.1021/acs.est.0c07846 | bibcode = 2021EnST...55.6729B }}

Fenofibrate was first synthesized in 1974, as a derivative of clofibrate, and was initially offered in France. It was initially known as procetofen, and was later renamed fenofibrate to comply with World Health Organization International Nonproprietary Name guidelines.{{cite journal | vauthors = Lalloyer F, Staels B | title = Fibrates, glitazones, and peroxisome proliferator-activated receptors | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 30 | issue = 5 | pages = 894–899 | date = May 2010 | pmid = 20393155 | pmc = 2997800 | doi = 10.1161/ATVBAHA.108.179689 }}

Fenofibrate was developed by Groupe Fournier SA of France.{{cn|date=May 2025}}

In the United States, Tricor was reformulated in 2005. This reformulation was controversial, seen as an attempt to stifle competition from generic equivalents,{{cite web|date=1 June 2006|title=Abbott's request to dismiss the antitrust charge over Tricor was rejected |url=http://www.fdanews.com/newsletter/article?issueId=9284&articleId=87219|work=FDANews, Drug Daily Bulletin}}{{dead link|date=May 2025}} and was the subject of antitrust litigation by Teva.

• Tricor by AbbVie
• Lipofen by Kowa Pharmaceuticals America Inc
• Lofibra by Teva
• Lipanthyl, Lipidil, Lipantil micro and Supralip by Abbott Laboratories
• Fenocor-67 by Ordain Health Care
• Fenogal by SMB Laboratories
• Antara by Oscient Pharmaceuticals
• Tricheck by Zydus (CND)
• Atorva TG by Zydus Medica
• Golip by GolgiUSA
• Stanlip by Sun Pharma (India)

A systematic review and meta-analysis found that fenofibrate might be a safe adjunct to neonatal phototherapy. However, the certainty of evidence was very low.{{cite journal | vauthors = Abdellatif M, Abozaid AA, Shah PS, Dhouibi N, Nguyen-Khac T, Khleif R, Luu MN, Quyen DK, Mohareb A, Vaghela G, Khan ZA, Pham HN, Makram AM, Huy NT | title = Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses | journal = Canadian Journal of Physiology and Pharmacology | volume = 102 | issue = 4 | pages = 242–253 | date = April 2024 | pmid = 38011686 | doi = 10.1139/cjpp-2023-0213 }}

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