atorvastatin (Lipitor)
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Introduction
Tradename: Lipitor (atorvastatin calcium) generic Nov 30, 2011[12]
Indications
- hypercholesterolemia, prevention of cardiovascular events
- may be of benefit for hypertension without hypercholesterolemia[4]
- arteriosclerosis
- rheumatoid arthritis* (in combination with DMARDs)[6]
* not effective in cardiovascular risk reduction in patients with systemic lupus erythematosus (SLE)[13]
* benefits may be less for women[16]
Contraindications
- pregnancy (potentially teratogenic, risk may be small)
- of no benefit in diabetics undergoing hemodialysis[18]
Dosage
Tabs: 10, 20 & 40 mg.
Pharmacokinetics
- oral dose is rapidly absorbed (may take with food)
- bioavailability is 14%[19]
- time to peak plasma concentrations is 1-2 hour
- protein binding is >98%
- metabolized by cyt P450 3A4
- not a prodrug
- active ortho & para-hydroxylated derivatives
- substrate of p-glycoprotein[19]
- 1/2 life is 14 hours
- undergoes enterohepatic circulation
- maximal effect on plasma cholesterol in 2 weeks
- crosses blood brain barrier
elimination via liver
1/2life = 14 hours
protein binding = 98 %
Monitor
Adverse effects
- gastrointestinal (most common)
- musculoskeletal
- neurologic
- increased risk of hemorrhagic stroke (RR=1.68)[7]
- endocrine: increased risk of type 2 diabetes[9]
- risk may be greater among women[16]
- potentially teratogenic
- drug adverse effects of HMG CoA reductase inhibitors
- drug adverse effects of anti-hyperlipidemic agents
Drug interactions
- limit dose of atorvastatin to 10 mg/day with coadministration of cyclosporine, tacrolimus, everolimus, sirolimus
- any drug which inhibits cyt P450 3A4 can increase atorvastatin levels: i.e. erythromycin
- any drug which induces cyt P450 3A4 can diminish atorvastatin levels
- risk of myopathy increased with concurrent administration of
- erythromycin, clarithromycin
- fibrates (gemfibrozil)
- niacin
- azole anti-fungal agents
- close monitoring for myalgia with coadministration of colchicine[19]
- atorvastatin decreases digoxin levels (20%)
- atorvastatin increases estrogen levels in women taking oral contraceptives 7 ) no dose limitation in combination with ticagrelor[19]
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of statins with vitamin D
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of statins with influenza virus vaccines
- drug interaction(s) of statins with macrolide
- drug interaction(s) of statins with antiviral protease inhibitors
- drug interaction(s) of statins with fibrates
- drug interaction(s) of atorvastatin with anthracycline
Mechanism of action
- inhibition of HMG CoA reductase
- maximal effect (80 mg/day)
- total cholesterol: decrease of 45%
- LDL cholesterol: decrease of 55%
- HDL cholesterol: increase of 5%
- triglycerides: decrease of 10-45%
- high doses of rosuvastatin & atorvastatin result in similar atherosclerosis regression, despite greater reductions in LDL cholesterol with rosuvastatin[11]
- does not seem to reduce inflammation in patients with SLE[13]
Notes
- not inferior to rosuvastatin in reducing atherosclerosis[10]
More general terms
Additional terms
- ASCOT LLA trial
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- fibrate
Component of
References
- ↑ Parke Davis package insert
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 4.0 4.1 Journal Watch 23(10):77, 2003 Sever PS et al, Lancet 361(Apr 5):1149, 2003 Lindhol LH & Samuelsson O, Lancet 361(Apr 5):1144, 2003
- ↑ 5.0 5.1 Journal Watch 22(12):91, 2002
Gaist D, Jeppesen U, Andersen M et al, Statins and risk of polyneuropathy: a case-control study. Neurology. 2002 May 14;58(9):1333-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12011277 - ↑ 6.0 6.1 Journal Watch 24(15):119, 2004 McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004 Jun 19;363(9426):2015-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15207950
- ↑ 7.0 7.1 Goldstein LB et al, SPARCL investigators Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Level Study. Neurology 2007 http://dx.doi.org/10.1212/01.wnl.0000296277.63350.77 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18077795)
- ↑ Prescriber's Letter 17(6): 2010 CHART: Characteristics of the Various Statins CHART: Clinically Significant Statin Drug Interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260611&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Waters DD et al Predictors of New-Onset Diabetes in Patients Treated With Atorvastatin J Am Coll Cardiol, 2011; 57:1535-1545 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21453832 <Internet> http://content.onlinejacc.org/cgi/content/abstract/57/14/1535
- ↑ 10.0 10.1 HealthDay News, Nov 29, 2011
- ↑ 11.0 11.1 Nicholls SJ et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011 Nov 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22085316 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1110874
- ↑ 12.0 12.1 Press Release: Watson Launches Generic Lipitor Nov 30, 2011 http://ir.watson.com/phoenix.zhtml?c=65778&p=irol-newsArticle&ID=1634538&highlight=
FDA News Release: Nov. 30, 2011 FDA approves first generic version of cholesterol-lowering drug Lipitor http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm281817.htm - ↑ 13.0 13.1 13.2 Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis. 2011 May;70(5):760-5 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21177297
- ↑ AstraZeneca announces top-line results from SATURN study http://www.astrazeneca.com/Media/Press-releases/Article/02092011-astrazeneca-saturn-study-results
- ↑ Deprecated Reference
- ↑ 16.0 16.1 16.2 Herman AO Lipitor Lawsuits Among Women Soar in Past 5 Months. Physician's First Watch, Aug 11, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ 17.0 17.1 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 18.0 18.1 Wanner C, Krane V, Marz W et al Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005 Jul 21;353(3):238-48. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16034009 Free Article
- ↑ 19.0 19.1 19.2 19.3 19.4 Wiggins BS, Saseen JJ, Page RL 2nd et al Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease. A Scientific Statement From the American Heart Association. Circulation. 2016;134:00-00 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27754879 <Internet> http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf
- ↑ Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367(20):1891-1900 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23113833 Free Article
- ↑ Gupta A, Thompson D, Whitehouse A et al Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. May 2, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28476288 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31075-9/fulltext?elsca1=tlpr
Pedro-Botet J, Rubies-Prat J. Statin-associated muscle symptoms: Beware of the nocebo effect. Lancet 2017 May 2 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28476289 <Internet> http://www.jwatch.org/na44073/2017/05/25/muscle-symptoms-statin-users-might-be-nocebo-effect - ↑ Herrett E, Williamson E, Brack K et al Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021 Feb 24;372:n135 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33627334
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60823
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2250
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60822
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656846
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62976