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Systematic (IUPAC) name
7-[4-(4-fluorophenyl) -6-(1-methylethyl)- 2-(methyl-methylsulfonyl-amino)- pyrimidin-

5-yl]- 3,5-dihydroxy-hept-6-enoic acid

CAS number 287714-41-4
ATC code C10AA07
PubChem 6439133
DrugBank APRD00546
Chemical data
Formula C22H28FN3O6S 
Mol. mass 481.539
Pharmacokinetic data
Bioavailability 20%
Metabolism Liver
Half life 19 hours
Excretion Urine / Faeces
Therapeutic considerations
Pregnancy cat.


Legal status

Prescription Only (S4)(AU) POM(UK) -only(US)

Routes oral

Rosuvastatin is a member of the drug class of statins, used to treat hypercholesterolemia and related conditions, and to prevent cardiovascular disease. It is currently being marketed by the pharmaceutical company AstraZeneca as Crestor.



Rosuvastatin is available as Crestor in tablet form (5, 10, 20, or 40 mg) for oral administration. Tablets are pink, round or oval (40 mg), biconvex, film-coated, and imprinted with "ZD4522" and tablet strength.[1] Japanese approval is in the dose range of 2.5 mg to 20 mg; therefore, smaller dose tablet forms might also be available outside the United States. Note that 97% of worldwide sales have been at or below the 20 mg dose.

Mechanism of action

Further information: Statin

Rosuvastatin is a competitive inhibitor of the enzyme HMG-CoA reductase, having a mechanism of action similar, yet higher efficacy, to other statins.[2]

Indications and regulation

Rosuvastatin is approved for the treatment of elevated LDL cholesterol (dyslipidemia), total cholesterol (hypercholesterolemia) and/or triglycerides (hypertriglyceridemia).[1]

As of 2004, rosuvastatin had been approved in 154 countries and launched in 56. Approval in the United States by the FDA came on August 12, 2003.[3]

Effects on cholesterol levels

The effects of rosuvastatin on LDL cholesterol are dose-related. At the 10mg dose, the average LDL cholesterol reduction was found to be 46% in one trial. Increasing the dose from 10 mg to 40 mg gave a modest increase of an additional 9% absolute reduction in LDL levels (55% below baseline levels).[4]

Marketing and competition


The drug was billed as a super-statin during its clinical development; that it offered high potency and improved cholesterol reduction compared to rivals in the class. The main competitors to rosuvastatin are atorvastatin (Lipitor), and the combination product ezetimibe/simvastatin (Zetia+Zocor, together marketed as Vytorin by Merck & Co.). However, people can also combine ezetimibe with either rosuvastatin or atorvastatin and other agents on their own, for somewhat similar augmented response rates. So far, some published information for comparing rosuvastatin, atorvastatin and ezetimibe/simvastatin results is available, but many of the relevant studies are still in progress.[2]

First launched in 2003, sales of rosuvastatin were $129 million and $908 million in 2003 and 2004, respectively, with a total patient treatment population of >4 million by the end of 2004.

In 2006, a new series of commercials were shown on TV, under the drug's trade name "Crestor". In the ads, Mandy Patinkin walks through a building with a series of hallways and escalators, a metaphor for the claim that Crestor was created to help raise good cholesterol and lower the bad — the promotional-phrase used was "down with the bad, up with the good". Patinkin, per FDA guidelines, also stated that the drug (like all statins) should not be used by pregnant persons, and to consult a doctor about using Crestor.

Debate & criticisms

Several months after its introduction in Europe, Richard Horton, the editor of the medical journal The Lancet, criticised 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 relies too much on extrapolation from the lipid profile data and too little on hard clinical endpoints, which are available for other statins which 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 Sir Tom McKillop called the editorial "flawed and incorrect" and slammed the journal for making "such an outrageous critique of a serious, well-studied medicine."[5]

In 2004, the consumer interest organisation Public Citizen filed a Citizen's Petition with the FDA asking that Crestor be withdrawn from the US market. On March 11, 2005, the FDA issued a letter to Sidney M. Wolfe, M.D. of Public Citizen both (a) denying the petition and (b) providing an extensive detailed analysis of findings which demonstrated no basis for concerns about rosuvastatin compared with the other statins approved for marketing in the United States; the full text of the FDA letter is available on-line:[6].


As with all statins, there is a concern of rhabdomyolysis (a severe undesired side effect). The 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.[7] However, more recent, larger and more thorough reviews have actually demonstrated both slightly lower rates of myopathy for rosuvastatin than any of the other statins available within the United States and improved kidney function with all statin use, including rosuvastatin, see below.

Regarding myopathy and potential rhabdomyolysis, recent reviews of published data on all statins marketed in the US, and reviewed by the FDA, both pre and post-approval, have found that marked rises in the serum levels of muscle CK enzymes to 10 times normal or greater, the hallmark of serious muscle problems, remain very rare, 1:10,000 to 1:20,000 individuals. (For comparison, this incidence is about identical with that for acetaminophen (paracetamol), commonly purchased as Tylenol, an OTC agent about which most people rarely worry; accept as safe)

Cerivastatin, a statin recalled in 2001, was an exception; it had a higher myopathy response. For the statins still on the market in the US, reported toxicity levels has been highest for pravastatin, simvastatin next, atorvastatin next and rosuvastatin the lowest at similar milligram doses. Yet the efficacy of these agents to change blood LDLipoproteins levels, at the same milligram doses, is the exact opposite. So, from the standpoint of the rare but serious muscle toxicity events, rosuvastatin, as of mid-2005 has turned out to have the best therapeutic index of the currently available statins.

Renal effects

Recent reviews of published trial data, focusing on renal function, on placebo vs. statin, and tracking renal function over time have shown a small but distinct effect of statins to lessen renal dysfunction, when added to treatment (compared to placebo), and to slow the progression of further renal function decline over time.[citation needed] All the statins have a somewhat dose related response to increase urine protein levels. Because increased urine protein has long been relied upon as a warning sign of renal glomerular dysfunction, this increase as a result of statin treatment had been feared to indicate a negative effect on renal function.

However, all current evidence, see reference 6 and others, is that the increase in urinary protein is from the renal tubular cells, not the glomeruli, and is due to cholesterol synthesis inhibition within the tubular cells and is not associated with any decline in renal function. Instead, as mentioned above, clinical experience is that renal function, especially in those with partial renal failure, actually improves slightly and the rate of further decline decreases compared with those in the same trials who were randomized to the placebo agent.

Human trial evidence and better information

More recent human controlled research trial data continues to be more promising. One of the most recent was a 2 year trial of rosuvastatin treatment, the ASTEROID trial, in reported in 2006 that when several hundred people were treated with Crestor at the highest currently approved dose of 40 mg a day, IVUS showed some reversal of atherosclerotic plaque within the coronary arteries.[2]


  • Annual Report and Form 20-F, Information 2004 (PDF). AstraZeneca PLC (2005).
  • Annual Report and Form 20-F, 2003 (PDF). AstraZeneca PLC (2004). Retrieved on 2005-03-20.
  • McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M (2001). "Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.". Am J Cardiol 87 (5A): 28B-32B. PMID 11256847.


  1. ^ a b Core Data Sheet, Crestor Tablets (PDF). AstraZeneca PLC (June 17 2003). Retrieved on 2005-03-20. - NOTE: this is provider-oriented information and should not be used without the supervision of a physician.
  2. ^ a b c Nissen SE, Nicholls SJ, Sipahi I, et al (2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial" (PDF). JAMA 295 (13): 1556-65. doi:10.1001/jama.295.13.jpc60002. PMID 16533939.
  3. ^ "FDA Approves New Drug for Lowering Cholesterol", The Food and Drug Administration, August 12, 2003. Retrieved on 2005-03-20. 
  4. ^ Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW. (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. PMID 12860216.
  5. ^ Horton, Richard (October 25 2003). "The statin wars: why AstraZeneca must retreat.". Lancet 362 (9393): 1341. PMID 14585629. Retrieved on 2005-03-20. - No author is listed with the online abstract; full-text is not available free online.
    McKillop T (November 1 2003). "The statin wars.". Lancet 362 (9394): 1498. PMID 14602449. - Full-text is not available free online.
  6. ^ Food and Drug Administration. "Docket No. 2004P-0113/CP1".
  7. ^ FDA Alert (03/2005) - Rosuvastatin Calcium (marketed as Crestor) Information. The Food and Drug Administration (March 14, 2005). Retrieved on 2005-03-20. - This page is subject to change; the date reflects the last revision date.

FDA documents index


  • 11 March 2005: Letter from FDA to Public Citizen informing of the denial of Public Citizen's 4 March 2004 Citizen's Petition
  • 8 March 2005: Letter from FDA to AstraZeneca regarding "false or misleading claims regarding the superiority of Crestor".
  • 2 March 2005: FDA Public Health Advisory on Crestor (rosuvastatin), patient and healthcare provider information updated
  • 2 March 2005: Letter from FDA to AstraZeneca mandating changes to prescription labeling


  • 21 December 2004: Letter from FDA to AstraZeneca regarding "false or misleading safety claims" in a print ad
  • 4 November 2004: FDA Docket listing 2004P-0113, regarding Public Citizen's Citizens' Petition of 4 March 2004
  • 15 September 2004: FDA Docket listing 2004P-0113, regarding Public Citizen's Citizens' Petition of 4 March 2004
  • 1 September 2004: Letter from FDA to Public Citizen indicating that Public Citizen's 4 March 2004 Citizen's Petition is still under consideration.
  • 4 June 2004: FDA Docket listing 2004P-0113, regarding Public Citizen's Citizens' Petition of 4 March 2004
  • 18 May 2004: Letter from Public Citizen to FDA, update to Citizen's Petition of 4 March 2004
  • 6 March 2004: FDA Docket listing 2004P-0113, regarding Public Citizen's Citizens' Petition of 4 March 2004
  • 5 March 2004: Letter from FDA to Public Citizen acknowledging receipt of Citizen's Petition.
  • 4 March 2004: Letter from Public Citizen to FDA petitioning for the immediate removal of Crestor from the market


  • 12 August 2003: Letter from FDA to AstraZeneca, approval letter
  • 9 July 2003: Presentations to the Endocrinologoc (sic) and Metabolic Drugs Advisory Committee
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Rosuvastatin". A list of authors is available in Wikipedia.
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