Rosuvastatin chemical structure
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®.
Presentation
Rosuvastatin is available as Crestor in tablet form (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
See the article on statins for more details.
Rosuvastatin is a competitive inhibitor of the enzyme HMG-CoA reductase, having a mechanism of action similar to other statins.
Indications and regulation
Rosuvastatin is indicated for the treatment of elevated LDL cholesterol (dyslipidemia), total cholesterol (hypercholesterolemia) and/or triglycerides (hypertriglyceridemia).[2]
As of 2004, rosuvastatin had been approved in 67 countries and launched in 56. Approval in the United States by the FDA came on August 12, 2003.[3]
Marketing and competition
Marketing
The drug was billed as a super-statin during its clinical development, claimed to offer a high potency and improved cholesterol reduction compared to rivals in the class. Currently the main competition for Crestor is Vytorin by Merck & Co. (a combination of simvastatin (Zocor) and ezetimibe (Zetia)); unfortunately, there are no published studies showing which of the two drugs is more effective.
First launched in 2003, sales 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.
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. The manufacturer responded by claiming 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."[4]
In 2004, the consumer interest organisation Public Citizen filed a Citzen's Petition with the FDA asking that Crestor be withdrawn from the US market. In 2005, the FDA formally denied this petition.
Some doctors have been hesitant to prescribe rosuvastatin because studies have suggested that this drug has a higher incidence of rhabdomyolysis (a severe undesired side effect) than other statins; this negative impact on sales performance has been much more pronounced in the United States than in other countries. 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.[5]
References
- AstraZeneca PLC (2005). Annual Report and Form 20-F, Information 2004. Information from print version.
- AstraZeneca PLC (2004). Annual Report and Form 20-F, 2003. Retrieved 2005-03-20.
- McTaggart, F.; Buckett, L.; Davidson, R.; Holdgate, G.; McCormick, A.; Schneck, D.; Smith, G.; and Warwick, M. Preclinical and clinical pharmacology of rosuvastatin, a new 3-hydroxy- 3-methylglutaryl coenzyme A reductase inhibitor. Am J Cardiol 2001;87(5supp1);28-32. PMID 11256847.
Notes
- ⇧ AstraZeneca PLC (June 17, 2003). Core Data Sheet, Crestor Tablets. Retrieved 2005-03-20. NOTE: this is provider-oriented information and should not be used without the supervision of a physician.
- ⇧ ibid.
- ⇧ The Food and Drug Administration (August 12, 2003). FDA Approves New Drug for Lowering Cholesterol. Press Release. Retrieved 2005-03-20.
- ⇧ Horton, Richard (October 25, 2003). The statin wars: why AstraZeneca must retreat. The Lancet 362(9393), 1341. PMID 14585629. Retrieved 2005-03-20. No author is listed with the online abstract; full-text is not available free online.
McKillop, Tom (November 1, 2003). The statin wars. The Lancet 362 (9394), 1498. PMID 14602449. Full-text is not available free online.
- ⇧ Rosuvastatin Calcium (marketed as Crestor) Information (March 14, 2005). FDA Alert (03/2005). Retrieved 2005-03-20. This page is subject to change; the date reflects the last revision date.
External links
FDA documents index
2005
2004
2003
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