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| {{drugbox |
| | #REDIRECT [[Atorvastatin calcium#Pharmacology]] |
| |image=Lipitor.png
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| |width=200
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| |image2=Atorvastatin-3D-balls.png
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| |width=200px
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| |IUPAC_name = [R-(R*, R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5- (1-methylethyl)-3-phenyl-4- [(phenylamino)carbonyl]-1H- pyrrole-1-heptanoic acid
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| |CAS_number = 134523-00-5
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| | ATC_prefix=C10
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| | ATC_suffix=AA05
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| | PubChem=60823
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| | DrugBank=APRD00055
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| | C=33 | H=35 | F=1 | N=2 | O=5
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| |molecular_weight = 558.64
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| |bioavailability = 12%
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| |metabolism = [[Liver]]
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| |elimination_half-life = 14 hours
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| |excretion = [[Bile]]
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| |pregnancy_AU = D
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| |pregnancy_US = X
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| |pregnancy_category =
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| |legal_AU = S4
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| |legal_UK = POM
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| |legal_US = Rx-only
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| |legal_status =
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| |routes_of_administration = oral
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| }}
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| {{SI}}
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| {{CMG}}
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| ==[[Atorvastatin (patient information)|For patient information, click here]]==
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| ==Overview==
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| '''Atorvastatin''' ([[International Nonproprietary Name|INN]]) ({{pronEng|əˌtɔrvəˈstætən}}), marketed under the trade name '''Lipitor''' and several others, is a member of the drug class known as [[statin]]s, used for lowering [[cholesterol]]. Atorvastatin inhibits the rate-determining [[enzyme]] located in [[liver|hepatic tissue]] that produces [[mevalonate]], a small molecule used in the synthesis of cholesterol and other mevalonate derivatives. This lowers the amount of cholesterol produced which in turn lowers the total amount of [[Low density lipoprotein|LDL]] cholesterol.
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| With 2006 sales of US$12.9 billion under the brand name Lipitor, it is the largest selling drug in the world.<ref>{{cite news | last = Loftus | first = Peter | title = Pfizer's Lipitor Patent Reissue Rejected | publisher = The Wall Street Journal Online | url = http://online.wsj.com/article/SB118730255664700229.html }}</ref>
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| A similar drug, [[simvastatin]], is available as a cheaper generic alternative.<ref name=saul>{{cite web
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| |url=http://www.nytimes.com/2007/11/03/business/03generic.html?_r=1&oref=slogin&ref=todayspaper&pagewanted=all
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| |title=Maker of Lipitor Digs In to Fight Generic Rival
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| |first=Stephanie
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| |last=Saul
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| |coauthors=Alex Berenson
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| |publisher=The New York Times
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| }}</ref><ref>{{cite web
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| |url=http://www.timesonline.co.uk/tol/news/uk/health/article2634201.ece
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| |title=Statins are the right prescription
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| |first=Nigel
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| |last=Hawkes
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| |publisher=The Times (UK)}}</ref>
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| ==Pharmacology==
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| {{main|Statin}}
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| As with other statins, atorvastatin is a competitive [[Enzyme inhibitor|inhibitor]] of [[HMG-CoA reductase]]. Unlike most others, however, it is a completely [[Chemical synthesis|synthetic]] compound. HMG-CoA reductase catalyzes the reduction of [[HMG-CoA reductase pathway|3-hydroxy-3-methylglutaryl-coenzyme A]] (HMG-CoA) to [[mevalonate]], which is the [[Rate-determining step|rate-limiting step]] in hepatic [[cholesterol]] biosynthesis. Inhibition of the enzyme decreases ''[[de novo synthesis|de novo]]'' cholesterol synthesis, increasing expression of low-density lipoprotein receptors ([[Low density lipoprotein|LDL]] receptors) on [[hepatocyte]]s. This increases [[Low density lipoprotein|LDL]] uptake by the hepatocytes, decreasing the amount of LDL-cholesterol in the blood. Like other statins, atorvastatin also reduces blood levels of [[triglyceride]]s and slightly increases levels of [[High density lipoprotein|HDL-cholesterol]].
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| In clinical trials, adding [[ezetimibe]] (Zetia) to Lipitor lowered cholesterol more effectively than [[Vytorin]] (ezetimibe + simvastatin).
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| ==Clinical use==
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| ===Indications===
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| Atorvastatin is indicated as an adjunct to diet for the treatment of [[dyslipidemia]], specifically [[hypercholesterolaemia]]. It has also been used in the treatment of [[combined hyperlipidemia]].<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
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| In 2005, the PROVE IT-TIMI 22 trial compared 40mg/day pravastatin with 80mg/day atorvastatin.<ref name="Rouleau2005">{{cite journal |author=Rouleau J |title=Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial |journal=Am. J. Med. |volume=118 Suppl 12A |issue= |pages=28-35 |year=2005 |pmid=16356805 |doi=10.1016/j.amjmed.2005.09.014}}</ref> Taken directly from the results of the trial: "Standard treatment (statin) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin 40 mg/day) resulted in a 22% reduction in LDL cholesterol levels at 30 days compared with a 51% reduction with intensive therapy (atorvastatin 80 mg/day). At 2 years, a relative risk reduction of 16% (95% confidence interval, 5%-26%; P = 0.005) in the primary end point rate (death, myocardial infarction, documented unstable angina requiring hospitalization, coronary revascularization, or stroke) was seen in patients receiving intensive statin treatment compared with standard statin therapy. The benefit of intensive treatment was apparent as early as 30 days and was consistent over time. The PROVE IT-TIMI 22 data indicate that patients recently hospitalized for an ACS benefit from early and continued lowering of LDL cholesterol to levels substantially below current guideline recommendations."
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| ===Available forms===
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| '''Atorvastatin calcium''' tablets are currently marketed by [[Pfizer]] under the trade name '''Lipitor''', in tablets (10, 20, 40 or 80 mg) for oral administration. Tablets are white, elliptical, and film coated. In some countries it may also be known as: '''Sortis''', '''Torvast''', '''Torvacard''', '''Totalip''', '''Tulip''', '''Xarator''', '''Atorpic''', or '''Liprimar'''. It is also packaged in combination with other drugs, such as is the case with Pfizer's [[Caduet]].
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| ===Adverse effects===
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| {{dablink|For additional information see: [[Statin#Safety|Statins]]}}
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| Common [[adverse drug reaction]]s (≥1% of patients) associated with atorvastatin therapy include: [[myalgia]], mild transient gastrointestinal symptoms (diarrhea, constipation, passing gas), elevated hepatic [[transaminase]] concentrations, headache, insomnia, joint pain, and/or dizziness.<ref name="AMH2006" />
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| [[Myopathy]] and [[rhabdomyolysis]] occur in <0.1% of patients. Risk is increased in patients with [[renal failure|renal impairment]], serious concurrent illness; and/or concomitant use of drugs which inhibit [[CYP3A4]].<ref name="AMH2006" />
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| ==Patent challenge==
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| The size of the market for atorvastatin has prompted the [[generic drug]] manufacturing company Ranbaxy to challenge the validity of some of Pfizer's patents in patent courts across the world. As of March 2007, courts had mostly upheld the validity of Pfizer's original patent for atorvastatin, which is due to expire in European territories in 2011 (but 2007 in Canada). However a later patent for the specific [[enantiomer]] of the atorvastatin formula that is medically useful, which would have given Pfizer longer protection, has fared less well. Although upheld in the United States<ref>BBC News, [http://news.bbc.co.uk/1/hi/business/4542358.stm Patent ruling hits Ranbaxy shares], 19 December 2005</ref>, Spain, and Ecuador, the enantiomer patent has been declared invalid by courts in Austria, Australia, Canada, the Netherlands and the United Kingdom<ref>Duncan Bucknell, [http://duncanbucknell.com/scorecards/51/ The global Lipitor patent scorecard], retrieved 2007-03-03</ref>.
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| ==Simvastatin and Alternatives==
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| An independent analysis showed that, at commonly prescribed doses, atorvastatin and simvastatin have no [[statistical significance|statistically significant]] differences in reducing cardiovascular morbidity and mortality.<ref>{{cite journal |author=Zhou Z, Rahme E, Pilote L |title=Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention |journal=Am. Heart J. |volume=151 |issue=2 |pages=273–81 |year=2006 |pmid=16442888 |doi=10.1016/j.ahj.2005.04.003}}</ref>
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| *[http://www.lipitor.com Lipitor.com] – manufacturer's site
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| *[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a600045.html MedlinePlus Drug information: Atorvastatin (Systemic)] – information from USP DI Advice for the Patient
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| ==Further reading==
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| *{{cite journal |author=Maggon K |title=Best-selling human medicines 2002-2004 |journal=Drug Discov. Today |volume=10 |issue=11 |pages=739-42 |year=2005 |pmid=15922927 |doi=10.1016/S1359-6446(05)03468-9}}
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| *[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop?_nfpb=true&_pageLabel=prescribingInformation Lipitor: Prescribing Information.] (2004) Pfizer Ireland Pharmaceuticals.
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| {{Statins}}
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| [[Category:Statins]]
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| [[Category:Cardiology]]
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| [[Category:drugs]]
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| [[zh:阿托伐他汀]]
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