Sons of the American Revolution

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Sons_of_the_American_Revolution 

National Society
of the
Sons of the American Revolution

Emblem of the Sons of the American Revolution
Logo used by the SAR
Abbreviation	SAR, NSSAR
Motto	"Libertas et patria" (Latin) "Liberty and Country"
Established	April 30, 1889
Type	Patriotic-Hereditary society
Legal status	Federally chartered corporation
Purpose	Fraternal, patriotic, historical, charitable, educational
Headquarters	809 West Main Street, Louisville, Kentucky
Region served	Nationwide
Membership	35,111 (2019)
Official language	English
Affiliations	Daughters of the American Revolution Children of the American Revolution
Website	sar.org

Philadelphia Continental Chapter of the SAR at a ceremony commemorating the birth of General and President George Washington at the Tomb of the Unknown Revolutionary War Soldier in Washington Square, Philadelphia

The National Society of the Sons of the American Revolution (SAR or NSSAR) is an American congressionally chartered organization, founded in 1889 and headquartered in Louisville, Kentucky. A non-profit corporation, it has described its purpose as maintaining and extending "the institutions of American freedom, an appreciation for true patriotism, a respect for our national symbols, the value of American citizenship, [and] the unifying force of 'e pluribus unum' that has created, from the people of many nations, one nation and one people."

The members of the society are male descendants of people who served in the American Revolutionary War or who contributed to establishing the independence of the United States. It is dedicated to perpetuating American ideals and traditions, and to protecting the Constitution of the United States; the official recognition of Constitution Day, Flag Day, and Bill of Rights Day were established through its efforts. It has members in the United States, Canada, France, Germany, Mexico, Spain, Switzerland, and the United Kingdom.

The organization is distinct from the Sons of the Revolution, a separate descendants heritage organization founded on February 22, 1876 by businessman John Austin Stevens and members of The Society of the Cincinnati. SAR Founder William Osborn McDowell disagreed with the Sons of the Revolution requirement at that time that all state societies were to be subordinate to the New York society.

History

Theodore Roosevelt, a member of the organization, signed its Congressional Charter in 1906

The first organization of descendants of Revolutionary War patriots was established in San Francisco, California, in 1876. A group of men who were descendants of Revolutionary War veterans gathered to celebrate the centennial of the Declaration of Independence and the founding of the United States. They also wanted to honor the men and women who pledged their lives, fortunes, and livelihood to the striving for independence from Great Britain. This group formed an organization called the Sons of Revolutionary War Sires (SRWS). There is, however, no direct link between the SRWS and the SAR except that members of the SRWS were permitted to join the SAR after its founding in 1889.

The history of the SAR can be traced to the founding of the Sons of the Revolution, the New York Society which was organized in 1876. The SR was founded by John Austin Stevens who envisioned an aristocratic social and hereditary organization along the lines of the Society of the Cincinnati. In 1889 William Osborn McDowell, a New Jersey financier and businessman, organized the New Jersey Society of the Sons of the Revolution but was unwilling to accept the SR's requirement that other state societies be subordinate to the New York society. Furthermore, McDowell wanted the society to become more of a mass movement of descendants of Revolutionary patriots rather than an exclusive social club. As a result, McDowell organized the Sons of the American Revolution (SAR) at Fraunces Tavern in New York on April 30, 1889. This was the centennial for the inauguration of George Washington as the First President of the United States of America in 1789. SAR membership number 1 was assigned to McDowell. In addition to organizing the SAR, McDowell worked with six women to organize the National Society Daughters of the American Revolution on July 29, 1890.

The SAR was formally granted a congressional charter by an act of Congress under Title 36 of the United States Code on June 9, 1906. The act was signed by President Theodore Roosevelt, who was a member.

Sons of the American Revolution grave marker, Old Ship Burying Ground, Hingham, Massachusetts

Membership

Membership in the society is open to any male of "good repute" who can prove lineal bloodline descent from an ancestor who actively supported the American Revolution. Acceptable ancestors include:

• military veterans of the American Revolutionary War, including those who served in the Continental Army, Continental Navy, and state militias and navies
• signers of the Declaration of Independence
• members of the Continental Congress
• civilians who provided arms or supplies to the American cause
• people who served on political bodies supporting the Revolution, signed oaths of allegiance, or those who gave similar support to the Patriot cause.
• Soldiers and sailors from allied nations such as France and Spain who fought in support of American independence.

No state society or chapter may discriminate against an applicant on the basis of race or creed. The SAR claims a membership of over 37,000 members in over 550 chapters representing all 50 states in the United States, as well as societies in Canada, France, Spain, Germany, Switzerland, and the United Kingdom. Overall, about 200,000 descendants have been admitted since the founding of the S.A.R. in 1890.

Governance

Horace Porter, U.S. Ambassador to France, served as President-General of the Sons of the American Revolution from 1892 to 1897.

The governance of the Sons of the American Revolution is made up of 10 National (General) Officers, 15 Vice-Presidents that preside over separate geographical regions and a Trustee elected from each state and international society. These officers meet several times over the year to discuss business pertaining to the society. The National Officers meet at least four times during their term of office, unless special meetings are called. The Trustees meet twice each year at the Society's Headquarters in Louisville, Kentucky. These meetings, known as the Fall and Spring Leadership Meetings, are normally held in late September and early March. During the Leadership Meetings committee recommendations and the society's budget are approved. While only the National Officers, Vice-Presidents and Trustees have the right to vote on the floor, all SAR members are welcome to attend and may request appointment to committees. The National Officers and Trustees also meet during the National Congress held in late June or early July of each year. Unlike the Leadership Meetings which always take place at the Society's National Headquarters, the National Congress is held in different locations throughout the United States. Locations are often selected in order to honor a historical event in United States history or in the history of the SAR, and there is an effort to alternate the meetings between the Eastern and Western United States. The National Congress is responsible for electing the National Officers and approving changes to the Society's constitution, along with any other motions brought before it. In addition to the National Officers, Vice-Presidents and Trustees, State and International Society Presidents and specially elected delegates from each society also attend with voting privileges. The number of delegates are determined by each State or International Society's membership size.

In addition to the larger meetings previously listed, there are over 60 standing and special committees that SAR members are appointed to in order to oversee the Society's welfare. Some of these committees include: facilities, insurance, genealogy, library, merchandise, medals and awards. All SAR members are welcome to participate on committees and are appointed by the Society's President General for a one-year term. There are no term-limits and all committee members have the right to vote on the committee's decisions.

The President-General for 2019-2020 is John T. Manning He was sworn in as President-General at the 129th National Congress in Orange County, CA. The Executive Director is Don Shaw of the Kentucky Society.

Genealogical library

The National Society of the Sons of the American Revolution has held a collection of genealogical reference dating back to 1889. Materials were originally kept by the Secretary General or Registrar General up until 1926, when the materials were moved to the Registrar General's office in Washington, D.C., in 1927, this collection was moved to the recently purchased Sixteenth Street Headquarters Building, and the collection had grown to 914 books by 1933. From this point until the move of Headquarters from Washington, D.C., to Louisville, Kentucky, the book collection grew at a rapid pace, growing to approximately 25,000 items by 1988. At this point, the Library was on the Second floor of the Headquarters building on South Fourth Street, and possessed a 544-square-foot vault for books not out in the library due to space.

Because of continuing growth, the SAR Library was moved in 2010 to a renovated building on West Main Street in the heart of the Historic Museum District of downtown Louisville. By this point, the Library collection had grown to over 58,000 items, mostly covering the Revolutionary War period, but also containing other genealogical materials. The library collection includes family histories, state genealogy materials, federal censuses, Revolutionary War pension applications, and CD collections, and the library separates materials based on State. The library also provides access to online research databases, including Ancestry.com, Footnote.com, and Heritage Quest Online.

Merchandise

The society operates a Merchandise Department that sells items intended for both SAR members and the general public. Among the products available to the general public are: clothing apparel for men and women, Revolutionary War replicas such as Liberty Bells and Field Cannons, jewelry for men and women such as lapel pins and cuff links, along with cups, mugs, key-chains, books, CDs, videos and knickknacks. Items intended for SAR members only include: clothing, decals, license plate holders and frames, certificates and medals corresponding to SAR activities, medals designed to reward active and retired military personnel, firefighters, EMS, JROTC and ROTC, individuals involved in education, Eagle Scouts and many others.

The Merchandise Department is located on the lower level of the SAR Genealogical Library, located at 809 West Main Street, just across the street from the Louisville Slugger Museum & Factory.

Activities

Indiana Society SAR Color Guard appearing with the recreated 19th US Infantry at an outdoor Fourth of July concert with the Indianapolis Symphony Orchestra.

The society is involved in historical research, raising funds for local scholarships and educational awards, and preservation of sites and documents related to the American Revolution. The SAR petitioned Congress to store Revolutionary era documents in a fire-proof area and make them available to the public, leading to the creation of the National Archives. It is also active in cataloging and marking Revolutionary War patriot graves and conducts an annual Eagle Scout scholarship program. The society is active in promoting "patriotism," and was instrumental in the establishment of Constitution Day. Several SAR societies and chapters have active color guard groups that appear in various public and private venues as a means of community outreach.

The Sons of the American Revolution hosts two Leadership Meetings and one National Congress every year. The two leadership meetings are held in the Spring and Fall in Louisville, KY at the Brown Hotel. The National Congress is held at a different location every year during the Summer. The 2017 National Congress took place in Knoxville, Tennessee, while the 2018 Congress will take place in Houston, Texas.

SAR national headquarters

The SAR's national headquarters, located along Museum Row in downtown Louisville, Kentucky, contains the organization's administrative staff offices, SAR Genealogical Research Library, and the future site of an American Revolutionary War Education Center. The SAR is currently raising funds to finish the Center's development. The building houses original and copied art that commemorates important people and events of the Revolutionary War, as well as historical uniforms, flags, documents, and other colonial era pieces.

Symbolism of the SAR insignia

The SAR insignia consists of a Maltese cross surrounded by a garland, with a relief of George Washington in a center circle.

The cross's vertical bar represents the commandment "You Shall Love Your God"; the horizontal bar represents the commandment "You Shall Love Your Neighbor as Yourself." The four limbs are a reminder of the four cardinal virtues; its eight points represent eight spiritual injunctions:

1. To have spiritual contentment
2. To live without malice
3. To weep over your sins
4. To humble yourself at insults
5. To love justice
6. To be merciful
7. To be sincere and open-hearted
8. To suffer persecution

Surrounding the relief of Washington in the center are the words "LIBERTAS ET PATRIA," a reminder of the United States Declaration of Independence and the United States Constitution.

The insignia is normally worn suspended by a ribbon of blue, white and gold (buff) on the wearer's left breast. National officers and former state and chapter presidents wear the insignia suspended from a neck ribbon of the Society's colors.

On other occasions a rosette in the Society's colors is worn on the wearers left lapel.

Simvastatin

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Simvastatin 

 

Simvastatin

Clinical data
Pronunciation	/ˈsɪmvəstætɪn/
Trade names	Zocor, other
AHFS/Drugs.com	Monograph
MedlinePlus	a692030
License data	EU EMA: by INN US FDA: Simvastatin
Pregnancy category	AU: D US: X (Contraindicated)
Routes of administration	by mouth
ATC code	C10AA01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: P (Pharmacy medicines) when ≤10 mg/day, POM (Prescription only) when >10 mg/day. US: ℞-only
Pharmacokinetic data
Bioavailability	5%
Protein binding	95%
Metabolism	Hepatic (CYP3A4)
Elimination half-life	2 hours for simvastatin and 1.9 hours for simvastatin acid
Excretion	Renal 13%, faecal 60%
Identifiers
IUPAC name[show]
CAS Number	79902-63-9
PubChem CID	54454
IUPHAR/BPS	2955
DrugBank	DB00641
ChemSpider	49179
UNII	AGG2FN16EV
KEGG	D00434
ChEBI	CHEBI:9150
ChEMBL	ChEMBL1064
CompTox Dashboard (EPA)	DTXSID0023581
ECHA InfoCard	100.115.749
Chemical and physical data
Formula	C25H38O5
Molar mass	418.574 g·mol−1
3D model (JSmol)	Interactive image

Simvastatin, marketed under the trade name Zocor among others, is a lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.

Common side effects include constipation, headaches, and nausea. Serious side effects may include muscle breakdown, liver problems, and increased blood sugar levels. A lower dose may be needed in people with kidney problems. There is evidence of harm to the developing baby when taken during pregnancy and it should not be used by those who are breastfeeding. It is in the statin class of medications and works by decreasing the manufacture of cholesterol by the liver.

Simvastatin was patented by Merck in 1980, and came into medical use in 1992. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication and at a relatively low cost. Simvastatin is made from the fungus Aspergillus terreus. In 2017, it was the eighth most commonly prescribed medication in the United States, with more than 56 million prescriptions.

Medical uses

The primary uses of simvastatin are to treat dyslipidemia and to prevent atherosclerosis-related complications such as stroke and heart attacks in those who are at high risk. It is recommended to be used as an addition to a low-cholesterol diet.

In the Scandinavian Simvastatin Survival Study (a placebo-controlled, randomized clinical trial of five years' duration), simvastatin reduced overall mortality in people with existing cardiovascular disease and high LDL cholesterol by 30% and reduced cardiovascular mortality by 42%. The risks of heart attack, stroke, or needing a coronary revascularization procedure were reduced by 37%, 28%, and 37%, respectively.

The Heart Protection Study evaluated the effects of simvastatin in people with risk factors including existing cardiovascular disease, diabetes, or stroke, but having relatively low LDL cholesterol. In this trial, which lasted 5.4 years, overall mortality was reduced by 13% and cardiovascular mortality was reduced by 18%. People receiving simvastatin experienced 38% fewer nonfatal heart attacks and 25% fewer strokes.

Simvastatin has been used to explore whether statins have an effect on delaying on the onset and progression of age-related macular degeneration (AMD). Results from one trial showed participants assigned to simvastatin had lower odds (0.51 OR) of having AMD progression at three years compared to those assigned to placebo, though the results were not significant. Overall, evidence is insufficient to conclude that simvastatin has an effect in delaying the onset and progression of AMD.

Contraindications

Simvastatin is contraindicated with pregnancy, breastfeeding, and liver disease. Pregnancy must be avoided while on simvastatin due to potentially severe birth defects. Patients cannot breastfeed while on simvastatin due to potentially disrupting the infant's lipid metabolism. High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine. A lower dose is also recommended in people taking the calcium channel blockers, verapamil and diltiazem, as well as those taking amiodarone.

Adverse effects

Common side effects (>1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps. Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically. Serious allergic reactions to simvastatin are rare. If the following signs of a serious allergic reaction occur, seek medical attention immediately: rash, hoarseness itching/swelling, dizziness, or difficulty swallowing/breathing.

A type of DNA variant known as a single nucleotide polymorphism (SNP) may help predict individuals prone to developing myopathy when taking simvastatin; a study ultimately including 32,000 patients concluded the carriers of one or two risk alleles of a particular SNP, rs4149056, were at a five-fold or 16-fold increased risk, respectively. In 2012, the Clinical Pharmacogenetics Implementation Consortium has released guidelines regarding the use of rs4149056 genotype in guiding dosing of simvastatin and updated the guideline in 2014.

In March 2012, the U.S. Food and Drug Administration (FDA) updated its guidance for statin users to address reports of memory loss, liver damage, increased blood sugar, development of type 2 diabetes, and muscle injury. The new guidance indicates:

• FDA has found that liver injury associated with statin use is rare but can occur.
• The reports about memory loss, forgetfulness, and confusion span all statin products and all age groups. The FDA says these experiences are rare, but that those affected often report feeling "fuzzy" or unfocused in their thinking.
• A small increased risk of raised blood sugar levels and the development of type 2 diabetes have been reported with the use of statins.
• Some drugs interact with statins in a way that increases the risk of muscle injury called myopathy, characterized by unexplained muscle weakness or pain.

On 19 March 2010, the FDA issued another statement regarding simvastatin, saying it increases the risk of muscle injury (myopathy) when taken at high doses or at lower doses in combination with other drugs. The highest dose rate causes muscle damage in 610 of every 10,000 people in contrast to a lower dose, which causes muscle damage in eight of 10,000 people. The FDA warning, released again on 8 June 2011, suggested that high-dose "simvastatin should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury" and that it "should not be started in new patients, including patients already taking lower doses of the drug."

Interactions

Simvastatin has important interactions with grapefruit juice and other drugs, including some that are commonly used for the treatment of cardiovascular disease. These interactions are clinically important because increasing simvastatin serum levels above those normally provided by the maximum recommended dose increases the risk of muscle damage, including the otherwise rare and potentially fatal side effect of rhabdomyolysis.

Consuming large amounts of grapefruit juice increases serum levels of simvastatin by up to three-fold, increasing the risk of side effects. The FDA recommends that people taking statins should avoid consuming more than a quart (946 ml) of grapefruit juice per day.

Simvastatin also interacts with other drugs, including some used to treat cardiovascular problems. It should not be taken by people who are also taking the antifungal drugs fluconazole, itraconazole, or posaconazole; the antibiotics erythromycin, clarithromycin, or telithromycin; HIV protease inhibitors; the antidepressant nefazodone; the cardiovascular drug gemfibrozil; the immunosuppressant ciclosporin, or the endometriosis drug danazol. Reduced maximum doses of simvastatin apply for patients taking certain other drugs, including the cardiovascular drugs verapamil, diltiazem, amiodarone, amlodipine, and ranolazine.

Pharmacology

All statins act by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase pathway, the metabolic pathway responsible for the endogenous production of cholesterol. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration, but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration. This is a major piece of evidence that statins work in another way than the lowering of cholesterol (called pleiotropic effects).

The drug is in the form of an inactive lactone that is hydrolyzed after ingestion to produce the active agent. It is a white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol, and ethanol.

Simvastatin is an effective serum lipid-lowering drug that can decrease low density lipoprotein (LDL) levels by up to 50%. Simvastatin had been shown to interact with lipid-lowering transcription factor PPAR-alpha  and that interaction might control the neurotrophic action of the drug.

History

The development of simvastatin was closely linked with lovastatin. Biochemist Jesse Huff and his colleagues at Merck began researching the biosynthesis of cholesterol in the early 1950s.^[35] In 1956, mevalonic acid was isolated from a yeast extract by Karl Folkers, Carl Hoffman, and others at Merck, while Huff and his associates confirmed that mevalonic acid was an intermediate in cholesterol biosynthesis. In 1959, the HMG-CoA reductase enzyme (a major contributor of internal cholesterol production) was discovered by researchers at the Max Planck Institute. This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme.

By 1976, Akira Endo had isolated the first inhibitor, mevastatin, from the fungus Penicillium citrinium while working at Daiichi Sankyo in Japan. In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus. While developing and researching lovastatin, Merck scientists synthetically derived a more potent HMG-CoA reductase inhibitor from a fermentation product of A. terreus, which was designated MK-733 (later to be named simvastatin).

In 1994, publication of the results of the Scandinavian Simvastatin Survival Study (4S) provided the first unequivocal evidence that lowering LDL cholesterol via statin treatment reduces cardiovascular events and overall mortality. A total of 4,444 people with coronary heart disease 5.5 to 8.0 mmol/L were randomized to simvastatin treatment or placebo and followed for an average of 5 years. Compared to the placebo group, those treated with simvastatin experienced a 30% decrease in overall mortality, a 42% reduction in coronary death, a 34% reduction in major coronary events, and a 37% reduction in revascularization procedures.

Society and culture

Cost

Simvastatin is relatively inexpensive. The wholesale cost in some LMIC is around US$0.01 to 0.15 per 20 mg dose as of 2014. The defined daily dose is 30 mg per the World Health Organization. The price decreased from roughly US$1,200 to $40 per year of medication in LMIC following the patent expiring in 2006. In the United States, it costs about US$10 to 20 per month since patent protection ended. In the UK in 2008, the typical per-patient cost to the NHS of simvastatin was about £1.50 per month. (40 mg/day costs UK NHS £1.37/month in 2012) The price in Canada is about $CAD 130 to 160 per year as of 2016. Under provisions of the Patient Protection and Affordable Care Act (PPACA) in the United States, there is no cost for simvastatin 10 mg, 20 mg, and 40 mg for adults aged 40–75 years based on United States Preventive Services Task Force (USPSTF) recommendations.

Economics

Simvastatin was introduced in the late 1980s, and since 2006 in many countries, it is available as a generic preparation. This has led to a decrease of the price of most statin drugs, and a reappraisal of the health economics of preventive statin treatment.

Prior to losing U.S. patent protection, simvastatin was Merck & Co.'s largest-selling drug and second-largest selling cholesterol-lowering drug in the world. In 2005, recorded US$3.1 billion of sales in the United States and US$4.4 billion worldwide.

Zocor had an original patent expiry date of 24 December 2005 but was extended by the United States Patent and Trademark Office (USPTO) to expire on 23 June 2006. The USPTO granted the patent extension after Merck submitted data from studies of the drug's positive effect on children. In the UK, the patent for simvastatin had expired by 2004.

In the UK, simvastatin was the most prescribed medication in the community in 2013, with 39.9 million items dispensed. This compares to 30.9 million items for aspirin, and 27.7 million for levothyroxine sodium, the second- and third-most prescribed drugs in the UK in 2013.

Marketing

Simvastatin was initially marketed by Merck & Co under the trade name Zocor but is available generically in most countries following the patent expiry. A combination of simvastatin along with ezetimibe is sold under the brand name Vytorin and is jointly marketed by Merck and Schering-Plough.

Brand names include Zocor, Zocor Heart Pro, marketed by the pharmaceutical company Merck & Co., Simlup, Simvotin, Simcard [India], Denan (Germany), Liponorm, Sinvacor, Sivastin (Italy), Lipovas (Japan), Lodales (France), Zocord (Austria and Sweden), Zimstat, Simvahexal (Australia), Lipex (Australia and New Zealand), Simvastatin-Teva, Simvacor, Simvaxon, Simovil (Israel), available in Thailand under the brand Bestatin manufactured by Berlin Pharmaceutical Industry Co Ltd and others.

The U.S. patent for Zocor expired on 23 June 2006. Ranbaxy Laboratories (at the 80-mg strength) and Teva Pharmaceutical Industries through its Ivax Pharmaceuticals unit (at all other strengths) were given approval by the FDA to manufacture and sell simvastatin as a generic drug with 180-day exclusivity. Dr. Reddy's Laboratories also has a license from Merck & Co. to sell simvastatin as an authorized generic drug.

Fenofibrate

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Fenofibrate 

 

Fenofibrate

Clinical data
Trade names	Fenoglide, Lipofen, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601052
License data	EU EMA: by INN US DailyMed: Fenofibrate
Pregnancy category	AU: B3 US: N (Not classified yet)
Routes of administration	By mouth
ATC code	C10AB05 (WHO) C10BA03 (WHO) C10BA04 (WHO)
Legal status
Legal status	UK: POM (Prescription only)  US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	99%
Metabolism	glucuronidation
Elimination half-life	20 h
Excretion	urine (60%), feces (25%)
Identifiers
CAS Number	49562-28-9
PubChem CID	3339
IUPHAR/BPS	7186
DrugBank	DB01039
ChemSpider	3222
UNII	U202363UOS
KEGG	D00565  C07586
ChEBI	CHEBI:5001
ChEMBL	ChEMBL672
CompTox Dashboard (EPA)	DTXSID2029874
ECHA InfoCard	100.051.234
Chemical and physical data
Formula	C20H21ClO4
Molar mass	360.83 g·mol−1
3D model (JSmol)	Interactive image
Melting point	80 to 81 °C (176 to 178 °F)

Fenofibrate, sold under the brand name Tricor among others, is a medication of the fibrate class used to treat abnormal blood lipid levels. It is less preferred to statin medications as it does not appear to reduce the risk of heart disease or death. Its use is recommended together with dietary changes. It is taken by mouth.

Common side effects include liver problems, breathing problems, abdominal pain, muscle problems, and nausea. Serious side effects may include toxic epidermal necrolysis, rhabdomyolysis, gallstones, blood clots, and pancreatitis. Use in pregnancy and breastfeeding is not recommended. It works by a number of mechanisms.

It was patented in 1969, and came into medical use in 1975. It is available as a generic medication. In 2017, it was the 70th most commonly prescribed medication in the United States with more than eleven million prescriptions.

Medical uses

Fenofibrate is mainly used for primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate appears to decrease the risk of cardiovascular disease and possibly diabetic retinopathy in those with diabetes mellitus, and firstly indicated for the reduction in the progression of diabetic retinopathy in patients with type 2 diabetes and existing diabetic retinopathy in Australia. It also appears to be helpful in decreasing amputations of the lower legs in this same group of people. Fenofibrate also has an off-label use as an added therapy of high blood uric acid levels in people who have gout.

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.

• Severe hypertriglyceridemia type IV or V

It is used in addition to diet for treatment of adults with severe hypertriglyceridemia. Improving glycemic control in diabetics showing fasting chylomicronemia will usually decrease 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.

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."

Contraindications

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
• Patients with known hypersensitivity to fenofibrate or fenofibric acid

Adverse effects

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

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

Precautions

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.

Musculoskeletal

• Myopathy and rhabdomyolysis; increased risk when coadminstered with a statin, particularly in the elderly and patients with diabetes, kidney failure, hypothyroidism

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.

Overdose

"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.

Interactions

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.
• 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
• 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.

Mechanism of action

"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 fibric acid 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.

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

Formulations

Fenofibrate is available in several formulations and is sold under several brand names, including 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, Fibractiv 105/35 by Cogentrix Pharma( India), Fenogal by SMB Laboratories, Antara by Oscient Pharmaceuticals, Tricheck by Zydus (CND), Atorva TG by Zydus Medica, Golip by GolgiUSA and Stanlip by Ranbaxy (India). Different 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.

The active form of fenofibrate, fenofibric acid, is also available in the United States, sold as Trilipix. Fenofibric acid may be taken without regard to the timing of meals.

Controversy

In the United States, Tricor was reformulated in 2005. This reformulation is controversial, as it is seen as an attempt to stifle competition from generic equivalents of the drug, and is the subject of antitrust litigation by generic drug manufacturer Teva. Also available in the United States, Lofibra is available in 54 and 160 mg tablets, as well as 67, 134, and 200;mg micronized capsules. Generic equivalents of Lofibra capsules are currently available in all three strengths in the United States. In Europe, it is available in either coated tablet or capsule; the strength range includes 67, 145, 160 and 200 mg. The differences among strengths are a result of altered bioavailability (the fraction absorbed by the body) due to particle size. For example, 200 mg can be replaced by 160 mg micronized fenofibrate. The 145 mg strength is a new strength that appeared in 2005-2006 which also replaces 200 or 160 mg as the fenofibrate is nanonised (i.e. the particle size is below 400 nm).

History

Fenofibrate was first synthesized in 1974, as a derivative of clofibrate, and was launched on the French market shortly thereafter. It was initially known as procetofen, and was later renamed fenofibrate' to comply with World Health Organization International Nonproprietary Name guidelines.

Fenofibrate was developed by Groupe Fournier SA of France, which was acquired in 2005 by Solvay Pharmaceuticals, a business unit of the Belgian corporation Solvay S.A.. In 2009, Solvay was, in turn, acquired by Abbott Laboratories (now AbbVie in the US and Mylan in Europe, Canada, Australia, New Zealand and Japan).

Research

COVID-19

In July 2020, researchers from Israel and the U.S. suggested that fenofibrate might significantly slow down the replication of the SARS-CoV-2 virus in lung cells. This hypothesis awaits testing in clinical trials.