Rosuvastatin, sold under the brand nameCrestor among others, is astatin medication, used to preventcardiovascular disease in those at high risk and treatabnormal lipids.[6] It is recommended to be used with dietary changes, exercise, and weight loss.[6] It is takenorally (by mouth).[6]
Rosuvastatin was patented in 1991 and approved for medical use in the United States in 2003.[6][7] It is available as ageneric medication.[6] In 2023, it was the twelfth most commonly prescribed medication in the United States, with more than 42million prescriptions.[8][9] In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.[10]
The effects of rosuvastatin onlow-density lipoprotein (LDL) cholesterol are dose-related. Higher doses are more effective at improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses ofatorvastatin and milligram-equivalent or higher doses ofsimvastatin andpravastatin.[11]
A meta-analysis showed that rosuvastatin can modestly increase the levels ofhigh-density lipoprotein (HDL) cholesterol in the blood, similar to other statins.[12] A 2014 Cochrane review determined there was good evidence for rosuvastatin lowering non-HDL levels linearly with dose.[13]
Rosuvastatin has multiplecontraindications, including hypersensitivity to rosuvastatin or any component of the formulation, active liver disease, elevation of serumtransaminases, pregnancy, or breastfeeding.[4] Rosuvastatin is not prescribed nor used while pregnant, as it can cause serious harm to the fetus.[4] With breastfeeding, it is unknown whether rosuvastatin is passed through breastmilk.[4][15]
Dose adjustments needs to be considered in individuals with renal failure. In mild to moderate renal failure (CLcr >30 to <60 mL/min/1.73 m2) a higher dose than 20mg daily is generally not recommended. Maximum dose of Rosuvastatin in patients with severe renal failure (CLcr < 30 mL/min/1.73 m2) withouthemodialysis is 10mg daily.[16]
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."[17][18][19] Therefore, the lowest dose is recommended in Asians.[20]
As with all statins, there is a concern ofrhabdomyolysis, 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.[21][22]
Statins increase the risk ofdiabetes,[23] consistent with FDA's review, which reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated people.[24]
Additional medications for high cholesterol such asclofibrate,fenofibrate,gemfibrozil, andniacin (when taken in lipid-modifying doses of 1 g/day and above)
Rosuvastatin has structural similarities with most otherstatins, e.g.,atorvastatin,cerivastatin andpitavastatin, but unlike other statins, rosuvastatin containssulfur (insulfonyl functional group).Crestor is acalcium salt of rosuvastatin, i.e., rosuvastatin calcium,[21] in which calcium replaces the hydrogen in thecarboxylic acid group on the right of the skeletal formula at the top right of this page.
Putative beneficial effects of rosuvastatin therapy on chronicheart failure may be negated by increases in collagen turnover markers as well as a reduction in plasmacoenzyme Q10 levels in patients with chronic heart failure.[28]
The dose-related magnitude of rosuvastatin on blood lipids was determined in aCochrane 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%.[13]
Absolutebioavailability of rosuvastatin is about 20% andCmax is reached in 3 to 5 hours; administration with food did not affect theAUC according to the original sponsor submitted clinical study and as per product label.[4] However, a subsequent clinical study has shown a marked reduction in rosuvastatin exposure when administered with food.[29] It is 88%protein bound, mainly toalbumin.[6] Fraction absorbed of rosuvastatin is frequently misquoted in the literature as approximately 0.5 (50%)[30] due to a miscalculated hepatic extraction ratio in the original submission package subsequently corrected by the FDA reviewer.[31]
Rosuvastatin is metabolized mainly byCYP2C9, but is not extensively metabolized; approximately 10% is recovered asmetaboliteN-desmethyl rosuvastatin. It is excreted infeces (90%) primarily and theelimination half-life is approximately 19 hours.[4][6]
Both AUC and Cmax are approximately 2-fold higher in Asian patients compared to Caucasian patients given the same dose of rosuvastatin.[4]
Because low- to moderate dose statins are strongly recommended by theUnited States Preventive Services Task Force (USPSTF) forprimary prevention of cardiovascular disease in adults aged 40–75 years who are at risk,[33] thePatient 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 acopayment orcoinsurance, even if he or she has not yet reached his or her annualdeductible.[34][35][36] Rosuvastatin 5 mg and 10 mg are examples of regimens meeting the USPSTF guideline;[33] however, insurers have discretion as to which low- and moderate-dose statin regimens to cover under this requirement,[37] and some only cover other statins.[38]
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 areatorvastatin andsimvastatin. However, people can also combineezetimibe with either simvastatin or atorvastatin and other agents on their own, for somewhat similar augmented response rates. As of 2006[update] some published information for comparing rosuvastatin, atorvastatin, and ezetimibe/simvastatin results are available, but many of the relevant studies are still[when?] in progress.[27][needs update]
First launched in 2003, sales of rosuvastatin were $129million and $908million in 2003 and 2004 respectively, with a total patient treatment population of over 4million by the end of 2004.[citation needed]Annual cost to the UKNational 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.[39]
In 2013, it was the fourth-highest-selling drug in the United States, accounting for approximately $5.2billion in sales.[40] In 2021, it was the thirteenth most commonly prescribed medication in the United States, with more than 32million prescriptions.[41]
As of 2004[update], rosuvastatin had been approved in 154 countries and launched in 56. Approval in the United States by theFood and Drug Administration (FDA) came on 13 August 2003.[44][45]
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.[46][47][48][49][50]
In April 2016, the FDA approved the firstgeneric version of rosuvastatin (from Watson Pharmaceuticals Inc).[51] In July 2016,Mylan gained approval for its generic rosuvastatin calcium.[52]
In October 2003, several months after its introduction in Europe,Richard Horton, the editor of themedical journalThe 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 inThe Lancet, AstraZeneca's CEOTom McKillop called the editorial "flawed and incorrect" and slammed the journal for making "such an outrageous critique of a serious, well-studied medicine."[53]
In 2004, the consumer interest organizationPublic Citizen filed aCitizen's Petition with the FDA, asking that Crestor be withdrawn from the US market. On 11 March 2005, the FDA issued a letter toSidney 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.[54] 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 inglycated hemoglobin (HbA1C) and fastinginsulin levels, and decreasedinsulin 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?"[55]
^Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. (2003). "Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial)".Am J Cardiol.92 (2):152–60.doi:10.1016/S0002-9149(03)00530-7.PMID12860216.
^abc"Rosuvastatin".MedlinePlus. U.S. National Library of Medicine. 15 June 2012.Archived from the original on 6 November 2012. Retrieved1 December 2012.
^"Rosuvastatin".LactMed. U.S. National Library of Medicine.Archived from the original on 7 January 2016. Retrieved1 December 2012.
^Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. (February 2010). "Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials".Lancet.375 (9716):735–42.doi:10.1016/S0140-6736(09)61965-6.PMID20167359.S2CID11544414.
^abNissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. (April 2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial".JAMA.295 (13):1556–65.doi:10.1001/jama.295.13.jpc60002.PMID16533939.
^Ashton E, Windebank E, Skiba M, Reid C, Schneider H, Rosenfeldt F, et al. (February 2011). "Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study".Int J Cardiol.146 (3):404–7.doi:10.1016/j.ijcard.2009.12.028.PMID20085851.
^Li Y, Jiang X, Lan K, Zhang R, Li X, Jiang Q (October 2007). "Pharmacokinetic properties of rosuvastatin after single-dose, oral administration in Chinese volunteers: a randomized, open-label, three-way crossover study".Clinical Therapeutics.29 (10):2194–203.doi:10.1016/j.clinthera.2007.10.005.PMID18042475.
^Bergman E, Lundahl A, Fridblom P, Hedeland M, Bondesson U, Knutson L, et al. (December 2009). "Enterohepatic disposition of rosuvastatin in pigs and the impact of concomitant dosing with cyclosporine and gemfibrozil".Drug Metabolism and Disposition.37 (12):2349–58.doi:10.1124/dmd.109.029363.PMID19773540.S2CID24783238.
^"COST COMPARISON CHARTS"(PDF). REGIONAL DRUG AND THERAPEUTICS CENTRE (NEWCASTLE). August 2018. Archived fromthe original(PDF) on 20 October 2018. Retrieved4 December 2018.
^"Core Data Sheet, Crestor Tablets"(PDF).AstraZeneca. June 17, 2003. Archived fromthe original(PDF) on May 8, 2005. RetrievedMarch 20, 2005. - NOTE: this is provider-oriented information and should not be used without the supervision of a physician.
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