Rosuvastatin

File:Crestor Tablets (rosuvastatin).jpg

The primary use of rosuvastatin is to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels in the blood.

The effects of rosuvastatin on low-density lipoprotein (LDL) cholesterol are dose-related. Higher doses were more efficacious in improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin.{{cite journal | vauthors=Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW | title=Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial) | journal=Am J Cardiol | year=2003 | volume=92 | issue=2 | pages=152–60 | pmid=12860216 | doi=10.1016/S0002-9149(03)00530-7}}

A meta-analysis showed that rosuvastatin can modestly increase the levels of high-density lipoprotein (HDL) cholesterol in the blood, similar to other statins.{{cite journal | vauthors = McTaggart F | title = Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit. | journal = Cardiovasc Drugs Ther| volume = 22 | issue = 4|date=August 2008 | pmid = 18553127 | pages = 321–38 | doi=10.1007/s10557-008-6113-z | pmc=2493531}} A 2014 Cochrane review determined there was good evidence for rosuvastatin lowering non-HDL levels linearly with dose.

Side effects are uncommon:{{cite web|title=Rosuvastatin|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a603033.html|work=MedlinePlus|publisher=U.S. National Library of Medicine|access-date=1 December 2012|date=15 June 2012|archive-date=6 November 2012|archive-url=https://web.archive.org/web/20121106160905/http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603033.html|url-status=live}}

• constipation
• heartburn
• dizziness
• sleeplessness
• depression
• joint pain
• cough
• memory loss or forgetfulness
• confusion

The following rare side effects are more serious. Like all statins, rosuvastatin can possibly cause myopathy, rhabdomyolysis:

• muscle pain, tenderness, or weakness
• lack of energy
• fever
• chest pain
• jaundice: yellowing of the skin or eyes
• dark colored, or foamy urine
• pain in the upper right part of the abdomen
• nausea
• extreme tiredness
• weakness
• unusual bleeding or bruising
• loss of appetite
• flu-like symptoms
• sore throat, chills, or other signs of infection

Allergic reactions can develop:

• rash
• hives
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• numbness or tingling in fingers or toes

Rosuvastatin has multiple contraindications, including hypersensitivity to rosuvastatin or any component of the formulation, active liver disease, elevation of serum transaminases, pregnancy, or breastfeeding.{{cite web | title=Crestor- rosuvastatin calcium tablet, film coated | website=DailyMed | date=9 November 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb0f3b5e-4bc6-41c9-66b9-6257e2513512 | access-date=14 March 2020 | archive-date=25 September 2020 | archive-url=https://web.archive.org/web/20200925143007/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb0f3b5e-4bc6-41c9-66b9-6257e2513512 | url-status=live }} Rosuvastatin is not prescribed nor used while pregnant, as it can cause serious harm to the fetus. With breastfeeding, it is unknown whether rosuvastatin is passed through breastmilk.{{cite web|title=Rosuvastatin|url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~jLYVIr:1|work=LactMed|publisher=U.S. National Library of Medicine|access-date=1 December 2012|archive-url=https://web.archive.org/web/20160107115521/http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?.%2Ftemp%2F~jLYVIr%3A1|archive-date=7 January 2016|url-status=dead}}

The risk of myopathy may be increased in Asian Americans: "Because Asians appear to process the drug differently, half the standard dose can have the same cholesterol-lowering benefit in those patients, though a full dose could increase the risk of side effects, a study by the drug's manufacturer, AstraZeneca, indicated."{{cite news |url=https://www.latimes.com/archives/la-xpm-2005-mar-03-na-crestor3-story.html |title=FDA Advisory Targets Asian Patients |work=Los Angeles Times |date=3 March 2005 | vauthors = Alonso-Zaldivar R |access-date=15 March 2020 |archive-date=5 March 2016 |archive-url=https://web.archive.org/web/20160305071949/http://articles.latimes.com/2005/mar/03/nation/na-crestor3 |url-status=live }}{{cite journal |vauthors=Wu HF, Hristeva N, Chang J, Liang X, Li R, Frassetto L, Benet LZ |title=Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions |journal=J Pharm Sci |volume=106 |issue=9 |pages=2751–2757 |date=September 2017 |pmid=28385543 |pmc=5675025 |doi=10.1016/j.xphs.2017.03.027 }}{{cite journal |vauthors=Lee VW, Chau TS, Leung VP, Lee KK, Tomlinson B |title=Clinical efficacy of rosuvastatin in lipid management in Chinese patients in Hong Kong |journal=Chin. Med. J. |volume=122 |issue=23 |pages=2814–9 |date=December 2009 |pmid=20092783 |url=https://journals.lww.com/cmj/FullText/2009/12010/Clinical_efficacy_of_rosuvastatin_in_lipid.3.aspx |access-date=30 October 2019 |archive-date=30 October 2019 |archive-url=https://web.archive.org/web/20191030192433/https://journals.lww.com/cmj/FullText/2009/12010/Clinical_efficacy_of_rosuvastatin_in_lipid.3.aspx |url-status=live }} Therefore, the lowest dose is recommended in Asians.{{cite web | title=FDA Updates Crestor Warning Information | website=WebMD | date=3 March 2005 | url=https://www.webmd.com/cholesterol-management/news/20050303/fda-updates-crestor-warning-information | access-date=14 March 2020 | archive-date=20 September 2020 | archive-url=https://web.archive.org/web/20200920092759/https://www.webmd.com/cholesterol-management/news/20050303/fda-updates-crestor-warning-information | url-status=live }}

As with all statins, there is a concern of rhabdomyolysis, a severe undesired side effect. The U.S. Food and Drug Administration (FDA) has indicated that "it does not appear that the risk [of rhabdomyolysis] is greater with Crestor than with other marketed statins", but has mandated that a warning about this side-effect, as well as a kidney toxicity warning, be added to the product label.{{cite web|title=FDA Alert (03/2005) - Rosuvastatin Calcium (marketed as Crestor) Information |url=https://www.fda.gov/cder/drug/infopage/rosuvastatin/default.htm |date=14 March 2005 |publisher=U.S. Food and Drug Administration (FDA) |access-date=20 March 2005 |archive-url=https://web.archive.org/web/20050305033448/https://www.fda.gov/cder/drug/infopage/rosuvastatin/default.htm |archive-date=5 March 2005 |url-status=dead }} - This page is subject to change; the date reflects the last revision date.{{cite web | title=Rosuvastatin Calcium (marketed as Crestor) Information | website=U.S. Food and Drug Administration (FDA) | date=10 July 2015 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/rosuvastatin-calcium-marketed-crestor-information | access-date=14 March 2020 | archive-date=15 December 2019 | archive-url=https://web.archive.org/web/20191215235005/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/rosuvastatin-calcium-marketed-crestor-information | url-status=live }}

Statins increase the risk of diabetes,{{cite journal | vauthors = Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I |title=Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.|journal=Lancet|date=February 2010|volume=375|issue=9716|pages= 735–42|pmid=20167359|doi=10.1016/S0140-6736(09)61965-6|s2cid=11544414 }} consistent with FDA's review, which reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated people.{{cite web |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-important-safety-label-changes-cholesterol-lowering-statin-drugs |title=FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs |publisher=U.S. Food and Drug Administration (FDA) |date=9 February 2019 |access-date=15 March 2020 |archive-date=15 March 2020 |archive-url=https://web.archive.org/web/20200315023515/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-important-safety-label-changes-cholesterol-lowering-statin-drugs |url-status=live }}

The following drugs can have negative interactions with rosuvastatin and should be discussed with the prescribing doctor:

• Coumadin anticoagulants ('blood thinners', e.g. warfarin) can affect the removal of rosuvastatin
• Ciclosporin, colchicine
• Drugs that may decrease the levels or activity of endogenous steroid hormones, e.g., cimetidine, ketoconazole, and spironolactone
• Additional medications for high cholesterol such as clofibrate, fenofibrate, gemfibrozil, and niacin (when taken in lipid-modifying doses of 1 g/day and above)
• Specific protease inhibitors including atazanavir (when taken with ritonavir), lopinavir/ritonavir and simeprevir
• Alcohol intake should be reduced while on rosuvastatin to decrease the risk of developing liver damage
• Aluminum and magnesium hydroxide antacids should not be taken within two hours of taking rosuvastatin
• Coadministration of rosuvastatin with eluxadoline may increase the risk of rhabdomyolysis and myopathy{{cite web | title=Viberzi- eluxadoline tablet, film coated | website=DailyMed | date=19 June 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7821bd40-4c84-4984-951b-6436ae20421a | access-date=14 March 2020 | archive-date=28 September 2020 | archive-url=https://web.archive.org/web/20200928020742/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7821bd40-4c84-4984-951b-6436ae20421a | url-status=live }}

Grapefruit juice negatively interacts with several specific drugs in the statin class, but it has little or no effect on rosuvastatin.{{cite journal | vauthors = Bailey DG, Dresser G, Arnold JM | title = Grapefruit-medication interactions: forbidden fruit or avoidable consequences? | journal = CMAJ | volume = 185 | issue = 4 | pages = 309–316 | date = March 2013 | pmid = 23184849 | pmc = 3589309 | doi = 10.1503/cmaj.120951 | doi-access = free }}

Rosuvastatin has structural similarities with most other statins, e.g., atorvastatin, cerivastatin and pitavastatin, but unlike other statins, rosuvastatin contains sulfur (in sulfonyl functional group).

Crestor is a calcium salt of rosuvastatin, i.e., rosuvastatin calcium, in which calcium replaces the hydrogen in the carboxylic acid group on the right of the skeletal formula at the top right of this page.{{citation needed|date=May 2022}}

{{Further|Statin}}

Rosuvastatin is a competitive inhibitor of the enzyme HMG-CoA reductase, having a mechanism of action similar to that of other statins.{{cite journal | vauthors = Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM |title=Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial |journal=JAMA |volume=295 |issue=13 |pages=1556–65 |date = April 2006 |pmid=16533939 |doi=10.1001/jama.295.13.jpc60002 |doi-access= | title-link=doi }}

Putative beneficial effects of rosuvastatin therapy on chronic heart failure may be negated by increases in collagen turnover markers as well as a reduction in plasma coenzyme Q₁₀ levels in patients with chronic heart failure.{{cite journal | vauthors = Ashton E, Windebank E, Skiba M, Reid C, Schneider H, Rosenfeldt F, Tonkin A, Krum H |title=Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study |journal=Int J Cardiol |volume= 146|issue= 3|pages= 404–7|date=February 2011 |pmid=20085851 |doi=10.1016/j.ijcard.2009.12.028 }}

The dose-related magnitude of rosuvastatin on blood lipids was determined in a Cochrane systematic review in 2014. Over the dose range of 1 to 80 mg/day, strong linear dose‐related effects were found; total cholesterol was reduced by 22.1% to 44.8%, LDL cholesterol by 31.2% to 61.2%, non-HDL cholesterol by 28.9% to 56.7%, and triglycerides by 14.4% to 26.6%.{{cite journal|title=Rosuvastatin for lowering lipids |journal=The Cochrane Database of Systematic Reviews|issue=11 | vauthors = Adams SP, Sekhon SS, Wright JM |date=November 2014 |volume=2014 |pages=CD010254|doi=10.1002/14651858.cd010254.pub2|pmid=25415541|pmc=6463960 | doi-access = free | title-link = doi }}

Absolute bioavailability of rosuvastatin is about 20% and C_max is reached in 3 to 5 hours; administration with food did not affect the AUC according to the original sponsor submitted clinical study and as per product label. However, a subsequent clinical study has shown a marked reduction in rosuvastatin exposure when administered with food.{{cite journal | vauthors = Li Y, Jiang X, Lan K, Zhang R, Li X, Jiang Q |date=October 2007|title=Pharmacokinetic properties of rosuvastatin after single-dose, oral administration in Chinese volunteers: a randomized, open-label, three-way crossover study|journal=Clinical Therapeutics|volume=29|issue=10|pages=2194–203|doi=10.1016/j.clinthera.2007.10.005|pmid=18042475 }} It is 88% protein bound, mainly to albumin. Fraction absorbed of rosuvastatin is frequently misquoted in the literature as approximately 0.5 (50%){{cite journal | vauthors = Bergman E, Lundahl A, Fridblom P, Hedeland M, Bondesson U, Knutson L, Lennernäs H |date=December 2009|title=Enterohepatic disposition of rosuvastatin in pigs and the impact of concomitant dosing with cyclosporine and gemfibrozil |journal=Drug Metabolism and Disposition|volume=37|issue=12|pages=2349–58|doi=10.1124/dmd.109.029363|pmid=19773540|s2cid=24783238 }} due to a miscalculated hepatic extraction ratio in the original submission package subsequently corrected by the FDA reviewer.{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor.cfm|title=Page 45 of FDA Drug Approval Package, Clinical Pharmacology Biopharmaceutics Review(s) (PDF)|date=29 January 2004|publisher=U.S. Food and Drug Administration (FDA)|access-date=22 June 2016|archive-date=28 August 2016|archive-url=https://web.archive.org/web/20160828094451/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor.cfm|url-status=live}}

Rosuvastatin is metabolized mainly by CYP2C9 and not extensively metabolized; approximately 10% is recovered as metabolite N-desmethyl rosuvastatin. It is excreted in feces (90%) primarily and the elimination half-life is approximately 19 hours.

Both AUC and C_max are approximately 2-fold higher in Asian patients compared to Caucasian patients given the same dose of rosuvastatin.

Rosuvastatin is the international nonproprietary name (INN).{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 45 | url = https://www.who.int/medicines/publications/druginformation/innlists/RL45.pdf | publisher = World Health Organization | access-date = 29 November 2016 | page = 50 | date = 2001 | archive-date = 18 May 2016 | archive-url = https://web.archive.org/web/20160518192927/http://www.who.int/medicines/publications/druginformation/innlists/RL45.pdf | url-status = live }}

Because low- to moderate dose statins are strongly recommended by the United States Preventive Services Task Force (USPSTF) for primary prevention of cardiovascular disease in adults aged 40–75 years who are at risk,{{cite journal | title=Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement | journal=American Family Physician | volume=95 | issue=2 | date=January 2017 | url=https://www.aafp.org/afp/2017/0115/od1.html | access-date=9 May 2022 | archive-date=3 August 2020 | archive-url=https://web.archive.org/web/20200803014843/https://www.aafp.org/afp/2017/0115/od1.html | url-status=live }} the Patient Protection and Affordable Care Act (PPACA) in the United States requires most health insurance plans to cover the costs of these drugs without charging the insured patient a copayment or coinsurance, even if he or she has not yet reached his or her annual deductible.{{cite web |title=Affordable Care Act (ACA)-Essential Health Benefit (EHB) Zero Dollar Copay Preventive Medication List White Paper |url=https://benefitoptions.az.gov/sites/default/files/PHARM_F_Essential_Health_Benefit_List.pdf |website=Arizona Department of Administration Human Resources |publisher=State of Arizona |access-date=8 May 2022 |archive-date=3 March 2022 |archive-url=https://web.archive.org/web/20220303022220/https://benefitoptions.az.gov/sites/default/files/PHARM_F_Essential_Health_Benefit_List.pdf |url-status=dead }}{{cite web |title=Preventive care benefits for adults |url=https://www.healthcare.gov/preventive-care-adults/ |website=Healthcare.gov |publisher=U.S. Centers for Medicare and Medicaid Services |access-date=7 May 2022 |archive-date=7 May 2022 |archive-url=https://web.archive.org/web/20220507192559/https://www.healthcare.gov/preventive-care-adults/ |url-status=live }}{{cite web |title=Preventive Services Covered by Private Health Plans under the Affordable Care Act |date=4 August 2015 |url=https://www.kff.org/health-reform/fact-sheet/preventive-services-covered-by-private-health-plans/ |publisher=Kaiser Family Foundation |access-date=7 May 2022 |archive-date=2 May 2022 |archive-url=https://web.archive.org/web/20220502082404/https://www.kff.org/health-reform/fact-sheet/preventive-services-covered-by-private-health-plans/ |url-status=live }} Rosuvastatin 5 mg and 10 mg are examples of regimens meeting the USPSTF guideline; however, insurers have discretion as to which low- and moderate-dose statin regimens to cover under this requirement,{{cite web | title=Affordable Care Act Implementation FAQs - Set 12 | website=CMS | date=22 April 2013 | url=https://www.cms.gov/CCIIO/Resources/Fact-Sheets-and-FAQs/aca_implementation_faqs12 | access-date=7 May 2022 | archive-date=5 May 2022 | archive-url=https://web.archive.org/web/20220505071209/https://www.cms.gov/CCIIO/Resources/Fact-Sheets-and-FAQs/aca_implementation_faqs12 | url-status=live }} and some only cover other statins.{{cite web|url=https://www.uhc.com/content/dam/uhcdotcom/en/Pharmacy/PDFs/UHC-SignatureValue-Formulary-PPACA-ZeroCost-Preventive-Meds-Eff-Sept-2021.pdf|date=September 2021|title=SignatureValue Zero Cost Share Preventive Medications PDL|website=Uhc.com|access-date=26 May 2022|archive-date=5 February 2022|archive-url=https://web.archive.org/web/20220205144210/https://www.uhc.com/content/dam/uhcdotcom/en/Pharmacy/PDFs/UHC-SignatureValue-Formulary-PPACA-ZeroCost-Preventive-Meds-Eff-Sept-2021.pdf|url-status=live}}

The drug was billed as a "super-statin" during its clinical development; the claim was that it offered high potency and improved cholesterol reduction compared to rivals in the class. The main competitors to rosuvastatin are atorvastatin and simvastatin. However, people can also combine ezetimibe with either simvastatin or atorvastatin and other agents on their own, for somewhat similar augmented response rates. {{as of|2006}} some published information for comparing rosuvastatin, atorvastatin, and ezetimibe/simvastatin results are available, but many of the relevant studies are still{{when|date=October 2019}} in progress.{{update inline|date=July 2021}}

First launched in 2003, sales of rosuvastatin were $129{{nbsp}}million and $908{{nbsp}}million in 2003, and 2004, respectively, with a total patient treatment population of over 4{{nbsp}}million by the end of 2004.{{Citation needed|date=January 2008}}

Annual cost to the UK National Health Service (NHS) in 2018, for 5–40 mg rosuvastatin daily (of one person) was £24-40, compared to £10-20 for 20–80 mg simvastatin.{{Cite web|url=http://gmmmg.nhs.uk/docs/cost_comparison_charts.pdf|title=COST COMPARISON CHARTS|publisher=REGIONAL DRUG AND THERAPEUTICS CENTRE (NEWCASTLE)|date=August 2018|access-date=4 December 2018|archive-date=20 October 2018|archive-url=https://web.archive.org/web/20181020032741/http://gmmmg.nhs.uk/docs/cost_comparison_charts.pdf|url-status=dead}}

In 2013, it was the fourth-highest-selling drug in the United States, accounting for approximately $5.2{{nbsp}}billion in sales.{{cite web|title=Top 100 Drugs for Q2 2013 by Sales|url=https://www.drugs.com/stats/top100/sales|access-date=24 August 2013|archive-date=23 June 2018|archive-url=https://web.archive.org/web/20180623222024/https://www.drugs.com/stats/top100/sales|url-status=live}} In 2021, it was the thirteenth most commonly prescribed medication in the United States, with more than 32{{nbsp}}million prescriptions.{{cite web | title=Rosuvastatin - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Rosuvastatin | access-date=14 January 2024}}

Rosuvastatin is approved in the United States for the treatment of high LDL cholesterol (dyslipidemia), total cholesterol (hypercholesterolemia), and/or triglycerides (hypertriglyceridemia).{{cite web | title=Core Data Sheet, Crestor Tablets | url=http://www.crestor.info/gUserFiles/CRESTOR_CDS_10_40_mg_FINAL_170603.pdf | date=17 June 2003 | publisher=AstraZeneca | access-date=20 March 2005 | archive-url=https://web.archive.org/web/20050508053622/http://www.crestor.info/gUserFiles/CRESTOR_CDS_10_40_mg_FINAL_170603.pdf | archive-date=8 May 2005 | url-status=dead | df=mdy-all }} - NOTE: this is provider-oriented information and should not be used without the supervision of a physician. In February 2010, rosuvastatin was approved by the FDA for the primary prevention of cardiovascular events.{{Cite report|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/021366s016ltr.pdf|publisher=U.S. Food and Drug Administration (FDA)|id=NDA 21366/S-016|title=Supplement approval - CRESTOR (rosuvastatin calcium) Tablets | vauthors = Colman EC |date=8 February 2010|access-date=31 October 2010|archive-date=17 October 2012|archive-url=https://web.archive.org/web/20121017170917/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/021366s016ltr.pdf|url-status=dead}}

{{As of|2004}}, rosuvastatin had been approved in 154 countries and launched in 56. Approval in the United States by the Food and Drug Administration (FDA) came on 13 August 2003.{{cite web | title=Drug Approval Package: Crestor (Rosuvastatin Calcium) NDA #021366 | website=U.S. Food and Drug Administration (FDA) | date=29 January 2004 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor.cfm | access-date=15 March 2020 | archive-date=6 August 2020 | archive-url=https://web.archive.org/web/20200806005318/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor.cfm | url-status=live }}{{cite news|title=FDA Approves New Drug for Lowering Cholesterol |url=https://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01247.html |date=12 August 2003 |publisher=U.S. Food and Drug Administration (FDA) |access-date=20 March 2005 |archive-url=https://web.archive.org/web/20050207153150/https://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01247.html |archive-date=7 February 2005 |url-status=dead }}

The main patent that protected rosuvastatin (RE37,314, which expired in 2016) was challenged as an improper reissue of an earlier patent. This challenge was rejected in 2010, and thus, patent protection continued until 2016.{{Cite web|url=http://www.delawareonline.com/article/20100701/BUSINESS/7010316/1003/RSS01|title=AstraZeneca's Crestor patent upheld;No generic competition until 2016|website=Delawareonline.com|access-date=26 May 2022}}{{Dead link|date=January 2023 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite press release| url=https://www.prnewswire.com/news-releases/crestor-patent-upheld-by-us-court-97435724.html| title=Crestor Patent Upheld By US Court| access-date=25 April 2012| publisher=AstraZeneca| date=29 June 2010| via=PR Newswire| archive-date=27 November 2020| archive-url=https://web.archive.org/web/20201127003059/https://www.prnewswire.com/news-releases/crestor-patent-upheld-by-us-court-97435724.html| url-status=live}}{{cite news| url=https://www.reuters.com/article/astrazeneca-crestor-idUSN2917115320100629| access-date=25 April 2012| date=29 June 2010| title=U.S. judge rules AstraZeneca Crestor patent valid| publisher=Reuters| vauthors = Berkrot B, Hals T | archive-date=12 March 2016| archive-url=https://web.archive.org/web/20160312124530/http://www.reuters.com/article/astrazeneca-crestor-idUSN2917115320100629| url-status=live}}{{cite news| url=https://pqasb.pqarchiver.com/delawareonline/access/2074695931.html?FMT=ABS&date=Jul+01%2C+2010| archive-url=https://archive.today/20130131145710/http://pqasb.pqarchiver.com/delawareonline/access/2074695931.html?FMT=ABS&date=Jul+01,+2010| url-status=dead| archive-date=31 January 2013| access-date=25 April 2012| title=AstraZeneca patent upheld| date=1 July 2010| newspaper=The News Journal| location=Wilmington, Delaware| vauthors = Starkey J | url-access=subscription }} {{subscription required}}{{cite press release | title=Crestor US patent upheld by Court of Appeals for the Federal Circuit | website=AstraZeneca | date=14 December 2012 | url=https://www.astrazeneca.com/media-centre/press-releases/2012/CRESTOR-US-patent-upheld-by-Court-of-Appeals-for-the-Federal-Circuit-14122012.html | access-date=9 July 2021 | archive-date=9 July 2021 | archive-url=https://web.archive.org/web/20210709193242/https://www.astrazeneca.com/media-centre/press-releases/2012/CRESTOR-US-patent-upheld-by-Court-of-Appeals-for-the-Federal-Circuit-14122012.html | url-status=live }}

In April 2016, the FDA approved the first generic version of rosuvastatin (from Watson Pharmaceuticals Inc).{{cite web|title=FDA approves first generic Crestor|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-crestor|publisher=U.S. Food and Drug Administration (FDA)|access-date=3 May 2016|date=29 April 2016|archive-date=15 March 2020|archive-url=https://web.archive.org/web/20200315024145/https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-crestor|url-status=dead}} In July 2016, Mylan gained approval for its generic rosuvastatin calcium.{{cite press release |url=https://www.prnewswire.com/news-releases/mylan-launches-generic-crestor-tablets-300301446.html |title=Mylan Launches Generic Crestor Tablets |date=20 July 2016 |publisher=Mylan |via=PR Newswire |access-date=15 March 2020 |archive-date=9 March 2021 |archive-url=https://web.archive.org/web/20210309012223/https://www.prnewswire.com/news-releases/mylan-launches-generic-crestor-tablets-300301446.html |url-status=live }}

In October 2003, several months after its introduction in Europe, Richard Horton, the editor of the medical journal The Lancet, criticized the way Crestor had been introduced. "AstraZeneca's tactics in marketing its cholesterol-lowering drug, rosuvastatin, raise disturbing questions about how drugs enter clinical practice and what measures exist to protect patients from inadequately investigated medicines," according to his editorial. The Lancet's editorial position is that the data for Crestor's superiority rely too much on extrapolation from the lipid profile data (surrogate end-points) and too little on hard clinical end-points, which are available for other statins that had been on the market longer. The manufacturer responded by stating that few drugs had been tested so successfully on so many patients. In correspondence published in The Lancet, AstraZeneca's CEO Tom McKillop called the editorial "flawed and incorrect" and slammed the journal for making "such an outrageous critique of a serious, well-studied medicine."{{cite journal | vauthors = Horton R | title = The statin wars: why AstraZeneca must retreat | journal = Lancet | volume = 362 | issue = 9393 | pages = 1341 | date = October 2003 | pmid = 14585629 | doi = 10.1016/S0140-6736(03)14669-7 | s2cid = 39528790 | title-link = doi | doi-access = free }}
{{cite journal | vauthors = McKillop T | title = The statin wars | journal = Lancet | volume = 362 | issue = 9394 | page = 1498 | date=November 2003 | pmid = 14602449 | doi = 10.1016/S0140-6736(03)14698-3| s2cid = 5300990 | doi-access = free }}

In 2004, the consumer interest organization Public Citizen filed a Citizen's Petition with the FDA, asking that Crestor be withdrawn from the US market. On 11 March 2005, the FDA issued a letter to Sidney M. Wolfe of Public Citizen both denying the petition and providing an extensive detailed analysis of findings that demonstrated no basis for concerns about rosuvastatin compared with the other statins approved for marketing in the United States.{{cite web | publisher=U.S. Food and Drug Administration (FDA) | title=Docket No. 2004P-0113/CP1 | url=https://www.regulations.gov/contentStreamer?documentId=FDA-2004-P-0009-0004&attachmentNumber=1&contentType=pdf | access-date=2 July 2020 | archive-date=2 July 2020 | archive-url=https://web.archive.org/web/20200702175551/https://www.regulations.gov/contentStreamer?documentId=FDA-2004-P-0009-0004&attachmentNumber=1&contentType=pdf | url-status=live }} In 2015, Wolfe explained why he thought that "the drug should have been withdrawn and why it should not be used", due to the incidence of rhabdomyolysis, renal problems, and significant increase in glycated hemoglobin (HbA_1C) and fasting insulin levels, and decreased insulin sensitivity in diabetic patients. Rosuvastatin indeed lowered cholesterol more than other statins, but Wolfe asked, "what about actually improving health, preventing heart attacks and strokes?"{{cite journal | vauthors = Wolfe S | title=Rosuvastatin: winner in the statin wars, patients' health notwithstanding | journal=BMJ| volume=350 | date=March 2015 | doi=10.1136/bmj.h1388|doi-access=free | pages=h1388 | title-link=doi | pmid = 25787130 }}

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