Varenicline 5108068 224980427 2008-07-11T08:20:09Z SJP 2716074 Reverted edits by [[Special:Contributions/125.16.142.113|125.16.142.113]] to last version by 76.241.132.173 (using [[WP:HG|Huggle]]) {{drugbox | | IUPAC_name = 7,8,9,10-tetrahydro-6,10-methano-<BR>6''H''-pyrazino(2,3-h)(3)benzazepine | image = Varenicline.svg | width = 155 | CAS_number = 249296-44-4 | CAS_supplemental = 375815-87-5 | ATC_prefix = N07 | ATC_suffix = BA03 | ATC_supplemental= | PubChem = 170361 | DrugBank = | C=13 | H=13 | N=3 | molecular_weight = 211.267 g/mol | smiles = <small>C1C2CNCC1C3=CC4=NC=CN=<BR>C4C=C23</small> | bioavailability = | protein_bound = <20% | metabolism = Limited (<10%) | elimination_half-life = 24 hours | excretion = [[Kidney|Renal]] (81&ndash;92%) | pregnancy_US = C | legal_status = Rx-only | dependency_liability = | routes_of_administration = Oral | licence_EU = Champix | licence_US = Varenicline }} '''Varenicline''' (trade name '''Chantix''' in the USA and '''Champix''' in Europe and other countries, marketed by [[Pfizer]], usually in the form of '''varenicline tartrate''') is a prescription medication used to treat smoking addiction. Varenicline is a [[nicotinic receptor]] [[partial agonist]]. In this respect, it is similar to [[cytisine]] and different from [[Receptor_antagonist|nicotinic antagonist]], [[bupropion]], and [[nicotine replacement therapy|nicotine replacement therapies]] (NRTs) like [[nicotine patch|nicotine patches]] (commonly, "the patch") and [[nicotine gum]]. As a partial agonist, it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products, and through these mechanisms, it can assist some patients in stopping smoking. ==Indications== Varenicline is indicated for (suggested for use in) smoking cessation. It is an alternative to NRTs and agonist medication and has demonstrated greater efficacy than them in comparable studies.<ref>{{cite journal | author = Jorenby D E, Hays J T, Rigotti N A, Azoulay S, Watsky E J, Williams K E, Billing C B, Gong J, Reeves K R| title = Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial | journal = JAMA| volume = 296|issue = 1|pages = 56–63| year = 2006 |pmid=16820547| doi = 10.1001/jama.296.1.56}}</ref> The FDA has approved its use for twelve weeks. If smoking cessation has been achieved it may be continued for another twelve weeks.<ref name=FDA>U.S. Food and Drug Administration. [http://www.fda.gov/bbs/topics/NEWS/2006/NEW01370.html ''FDA Approves Novel Medication for Smoking Cessation'']. Press release, 11 May 2006.</ref> Varenicline has not been tested in children, those under 18 years old, or pregnant women, and therefore is not recommended for use by these groups. Women currently breastfeeding should also avoid this product, since varenicline may pass into the breast milk, leading to unknown effects on the child. ==Mechanism of action== Varenicline is a [[partial agonist]] of the &alpha;<sub>4</sub>&beta;<sub>2</sub> subtype of the [[nicotinic acetylcholine receptor]]. In addition it acts on &alpha;<sub>3</sub>&beta;<sub>4</sub> and weakly on &alpha;<sub>3</sub>&beta;<sub>2</sub> and &alpha;<sub>6</sub>-containing receptors. A full agonism was displayed on &alpha;<sub>7</sub>-receptors.<ref name="pmid16766716">{{cite journal |author=Mihalak KB, Carroll FI, Luetje CW |title=Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors |journal=Mol. Pharmacol. |volume=70 |issue=3 |pages=801–5 |year=2006 |pmid=16766716 |doi=10.1124/mol.106.025130}}</ref> ==Pharmacokinetics== Most of the active compound is excreted renally (92-93%). A small proportion is [[glucuronidation|glucuronidated]], oxidated, ''N''-formylated or conjugated to a hexose.<ref>Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW. Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. ''Drug Metab Dispos'' 2006;34:121-30. PMID 16221753.</ref> The elimination half-life is about 24 hours. ==Side Effects== [[Nausea]] occurs commonly in people taking varenicline. Other less common side effects include [[headache]], [[insomnia|difficulty sleeping]], and abnormal [[dream]]s. Rare side effects reported by people taking varenicline compared to placebo include [[dysgeusia|change in taste]], [[vomiting]], [[abdominal pain]], [[flatulence]], and [[constipation]].<ref>{{cite web |url=http://www.cancer.org/docroot/CDG/content/CDG_Varenicline.asp |author=American Cancer Society|title=Cancer Drug Guide: Varenicline |accessdate=2008-01-19 |format= |work=}}</ref> In November 2007, the FDA announced it had received post-marketing reports that patients using Chantix for smoking cessation had experienced several serious symptoms, including [[suicidal ideation]] and occasional [[Suicide#Suicidal_gestures_and_attempts|suicidal behavior]], erratic behavior, and drowsiness. On February 1, 2008 the FDA issued an Alert to further clarify its findings, noting that "it appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms." It is unknown whether the [[psychiatry|psychiatric]] symptoms are related to the drug or to [[nicotine withdrawal]] symptoms, although not all patients had stopped smoking. The FDA is aware of the highly-publicized case of [[Carter Albrecht]] who, in an apparent state of delirium, was shot to death by his neighbour after hitting his girlfriend and then trying to forcibly enter the neighbor's house.<ref name="titleABC News: Did Quit-Smoking Pill Lead to Man's Death?">{{cite web |url=http://www.abcnews.go.com/GMA/OnCall/story?id=3623085&page=1 |title=ABC News: Did Quit-Smoking Pill Lead to Man's Death? |accessdate=2007-12-15 |author= |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> Although in this case the delirium appeared to be caused by taking varenicline with a high dose of alcohol, the FDA asked Pfizer for additional cases that might be similar. It also recommended that health care professionals and patients watch for behavioral and mood changes.<ref name="FDA safety">{{cite web |title= Early Communication About an Ongoing Safety Review: Varenicline (marketed as Chantix) |url= http://www.fda.gov/cder/drug/early_comm/varenicline.htm |publisher= United States [[Food and Drug Administration]] |month= November 20 |year= 2007 | accessdate= 2007-11-21 }}</ref> On Thursday, May 22, 2008, ''[[The New York Times]]'' reported that the U.S. Federal Aviation Administration (F.A.A.) had announced the day before a ban on the use of Chantix (varenicline tartrate) for both pilots and air traffic controllers, due to concerns with possible adverse neuropsychiatric effects which could be detrimental to public safety.<ref>{{cite news |first=Stephanie |last=Saul |title=F.A.A. Bans Antismoking Drug, Citing Side Effects |url=http://www.nytimes.com/2008/05/22/business/22drug.html |work=New York Times |date=2008-05-22 |accessdate=2008-05-22}}</ref> On Sunday, May 25, 2008, ''[[The Los Angeles Times]]'' reported that over 2 dozen traffic accidents had been linked to Chantix and reported to the FDA. Warnings had previously been issued by Pfizer regarding the risks of Chantix while driving, however these warnings have largely been ignored by doctors and patients.<ref>{{cite news |first=Ricardo |last=Alonso-Zaldivar |title=Drug taken to stop smoking is linked to traffic mishaps |url=http://www.latimes.com/news/nationworld/nation/la-na-smokedrug25-2008may25,0,6554950.story |work=Los Angeles Times |date=2008-05-25 |accessdate=2008-05-25}}</ref> On Tuesday, June 17, 2008, ''[[The Washington Times]]'' reported on its Front Page that the [[United States Department of Veterans Affairs]] was testing Chantix on war veterans with [[Post Traumatic Stress Disorder]] without properly warning them of the side effects, and that in one case a veteran was almost killed when he had a psychotic episode and threatened police officers.<ref>{{cite news |first=Audrey |last=Hudson |title=VA Testing Drugs on War Veterans |work=The Washington Times |date=2008-06-17 |page=A1}}</ref> ==History== Varenicline was discovered at Pfizer through the research aimed at modifying the structure of [[cytisine]],<ref>{{cite journal |author=Coe JW, Brooks PR, Vetelino MG, ''et al'' |title=Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation |journal=J. Med. Chem. |volume=48 |issue=10 |pages=3474–7 |year=2005 |pmid=15887955 |doi=10.1021/jm050069n}}</ref> a European smoking cessation aid and also a partial α4β2-nicotinic antagonist.<ref name="pmid515342">{{cite journal |author=Schwartz JL |title=Review and evaluation of methods of smoking cessation, 1969-77. Summary of a monograph |journal=Public Health Rep |volume=94 |issue=6 |pages=558–63 |year=1979 |pmid=515342}} {{PMC|1431736}}</ref><ref name="pmid16908787">{{cite journal |author=Etter JF |title=Cytisine for smoking cessation: a literature review and a meta-analysis |journal=Arch. Intern. Med. |volume=166 |issue=15 |pages=1553–9 |year=2006 |pmid=16908787 |doi=10.1001/archinte.166.15.1553| url=http://archinte.ama-assn.org/cgi/content/full/166/15/1553}}</ref> Varenicline received a "priority review" by the U.S. [[Food and Drug Administration]] in February 2006, shortening the usual 10-month review period to 6 months because of its demonstrated effectiveness in [[clinical trial]]s and perceived lack of safety issues.<ref name="pmid16467225">{{cite journal |author=Kuehn BM |title=FDA speeds smoking cessation drug review |journal=JAMA |volume=295 |issue=6 |pages=614 |year=2006 |pmid=16467225 |doi=10.1001/jama.295.6.614}}</ref> The agency's approval of the drug came on May 11, 2006.<ref name=FDA/>. Beginning August 1, 2006, varenicline has been available for sale in the United States, and on September 29, 2006, it was approved for sale in the [[European Union]]. ==Footnotes== {{reflist|2}} ==External links== {{wikinews|New drug for smoking cessation is under investigation}} * [http://www.chantix.com Official website] * [http://www.fda.gov/cder/drug/infopage/varenicline/default.htm FDA Alert] {{Drugs used in addictive disorders}} [[Category:Tobacco cessation]] [[Category:Pyrazines]] [[Category:Nicotinic agonists]] [[cs:Varenicline]] [[de:Vareniclin]] [[es:Vareniclina]] [[fr:Varénicline]] [[it:Vareniclina]] [[nl:Varenicline]] [[ja:バレニクリン酒石酸塩]] [[pl:Wareniklina]] [[pt:Vareniclina]] [[fi:Varenikliini]]