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rosuvastatin (Crestor)

Tradename: Crestor. FDA approves generics 4/16 [10,13]. Public Citizen pushed the FDA to take rosuvastatin (Crestor) off the market (2004) [2]; labeled a 'dangerous drug' [5] Indications: - adjunct to diet in treatment of primary hypercholesterolemia & mixed dyslipidemia - also see HMG CoA reductase inhibitor (statin) - prevention of cardiovascular disease - FDA approved to reduce risk of cardiovascular disease in patients without elevated LDL cholesterol but with elevated serum CRP - transient ischemic attack, ischemic stroke - post myocardial intection - peripheral vascular disease - arteriosclerosis - perioperative rosuvastatin (20 mg/day) begun 8 days prior to surgery & continued for 5 days after surgery does not reduce postoperative complications in patients undergoing elective cardiac surgery [11] Contraindications: 1) active liver disease [17] 2) caution giving > 20 mg/day a) chronic renal insufficiency b) hypothyroidism c) elderly (> 65 years of age) 3) do NOT exceed 20 mg/day in Japanese or Chinese 4) do NOT exceed 10 mg/day in patients with severe renal insufficiency Dosage: 1) 10-40 mg PO QD 2) start 5 mg QD (Asians, renal insufficiency, hypothyroidism, > 65 years of age) [4] Pharmacokinetics: 1) bioavailability about 20% [14] 2) mean volume of distribution 134 liters 3) maximum plasma levels reached in 3-5 hours [14] 4) not a prodrug, miminal activity of metabolites [14] 5) 28% renal clearance; 72% hepatic clearance after IV dose 6) 10% metabolized by cyt P450 2C9 (CYP2C9) 7) 90% excreted in the feces after oral dose [14] 8) 1/2life of 19 hours [14] 9) serum levels tend to be twice as high in Asians for a given dose [4] Dosage adjustment in renal failure: 1) increased plasma levels (up to 3-fold) observed when creatinine clearance < 30 mL/min 2) maximum dose 10 mg QD [4] Monitor: 1) liver function tests 2) urine protein (at 40 mg dose) 3) lipid panel baseline, at 1-3 months, thereafter every 3-12 months* * no substantial reason given except for assessment of medication compliance; no suggestion given how results of testing would =change management [12] Adverse effects: 1) hepatotoxicity (rare) - increased liver function tests 1% (same as other statins) 2) proteinuria (only statin associated with proteinuria) - rosuvastatin is associated with increased risk of hematuria, proteinuria, & ESRD compared wth atorvastatin [16] 3) patients with cardiovascular disease who took rosuvastatin vs atorvastatin had similar incidence of major cardiovascular events but higer incidence of new onset diabetes mellitus & need for cataract surgery [18] 4) myopathy/rhabdomyolysis [3] 5) potentially teratogenic Toxicity: - supportive care Drug interactions: 1) limit dose of rosuvastatin to 5 mg QD in combination with cyclosporine, tacrolimus, everolimus, sirolimus - increased rosuvastatin plasma levels in combination with cyclosporine 2) limit dose of rosuvastatin to 10 mg QD in combination with gemfibrozil (increased incidence of myopathy) [4,14] 3) oral contraceptives: rosuvastatin increases plasma levels of ethinyl estradiol (26%) & norgestrel (34%) 4) close monitoring for myopathy when used in combination with colchicine [14] 5) case report of myopathy, rhabdomyolysis & hepatotoxicity 15 days after statring canagliflozin (100 mg) in a patient who has been taking rosuvastatin (40 mg) for 5 years [15] Mechanism of action: 1) lowers LDL by 50% (10 mg QD) 2) increases HDL 10-14% (most effective statin) 3) high doses of rosuvastatin & atorvastatin result in similar atherosclerosis regression, despite greater reductions in LDL cholesterol with rosuvastatin [9] Notes: - not superior to atorvastatin in reducing atherosclerosis [8] - differences between rosuvastatin & atorvastatin are relatively small, & may not reach clinical significance - 6 year mortality lower for rosuvastatin vs atorvastatin (2.57 vs 2.83 & 0.66 vs 0.90 per 100 person years in 2 different databases [19] - rosuvastatin associated lower risks for major adverse cardiovascular events & major adverse liver outcomes than atorvastatin - risk for type 2 diabetes mellitus is higher with rosuvastatin than atorvastatin [19]

Interactions

drug interactions drug adverse effects (more general classes) monitor with HMG CoA reductase inhibitors (statins)

Related

A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) Jupiter study

General

hydrophilic statin

Properties

INHIBITS: HMG CoA reductase MISC-INFO: pregnancy-category X elimination by hemodialysis -

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 10(8):43 2003
  2. Prescriber's Letter 11(4):19-20 2004 Detail-Document#: 200402 (subscription needed) http://www.prescribersletter.com
  3. FDA Medwatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#crestor
  4. Prescriber's Letter 12(4): 2005 FDA Public Health Advisory on Crestor (rosuvastatin) Detail-Document#: 210402 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 12(7): 2005 The Safety of Crestor (Rosuvastatin) - An Update Detail-Document#: 210703 (subscription needed) http://www.prescribersletter.com
  6. Prescriber's Letter 15(12): 2008 COMMENTARY: Rosuvastatin (Crestor) for High C-Reactive Protein GUIDELINES: National Cholesterol Education Program (NCEP) Recommendations GUIDELINES: Markers of Inflammation and Cardiovascular Disease GUIDELINES: Canadian Cardiovascular Society Position Statement- Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease Detail-Document#: 241201 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 17(3): 2010 Rosuvastatin (Crestor) for High C-Reactive Protein (CRP) Detail-Document#: 260302 (subscription needed) http://www.prescribersletter.com
  8. AstraZeneca announces top-line results from SATURN study http://www.astrazeneca.com/Media/Press-releases/Article/02092011-astrazeneca-saturn-study-results
  9. Nicholls SJ et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011 Nov 15 PMID: 22085316 http://www.nejm.org/doi/full/10.1056/NEJMoa1110874
  10. Stiles S FDA Approves Generic Rosuvastatin (Crestor) Medscpape. April 29, 2016 http://www.medscape.com/viewarticle/862674 - FDA News Release. April 29, 2016. FDA approves first generic Crestor. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm498373.htm
  11. Zheng Z, Jayaram R, Jiang J et al Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med 2016; 374:1744-1753. May 5, 2016 PMID: 27144849
  12. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  13. NEJM Editors FDA Approves Additional Generic Versions of Rosuvastatin Physician's First Watch, July 21, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  14. 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 PMID: 27754879 http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf
  15. Brailovski E et al Rosuvastatin Myotoxicity After Starting Canagliflozin Treatment: A Case Report. Ann Intern Med. Aug 4, 2020 PMID: 32744865 https://www.acpjournals.org/doi/10.7326/L20-0549
  16. Busko M Rosuvastatin Again Linked With Risks to Kidneys Medscape. July 20, 2022 https://www.medscape.com/viewarticle/977646 - Shin JI, Fine DM, Sang Y et al Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria. J Am Soc Nephrol (JASN) July 2022, ASN.2022020135 PMID: 35853713 https://jasn.asnjournals.org/content/early/2022/07/19/ASN.2022020135
  17. Windle ML Rapid Rx Quiz: Statin Intolerance and Related Concerns Medscape. September 01, 2022 https://reference.medscape.com/viewarticle/979515
  18. Lee YJ et al. Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: Secondary analysis of the randomised LODESTAR trial. BMJ 2023 Oct 18; 383:e075837. PMID: 37852649 PMCID: PMC10583134 Free PMC article https://www.bmj.com/content/383/bmj-2023-075837
  19. Zhou S, Chen R, Liu J et al Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin: A Multi-database Cohort Study. Ann Intern Med. 2024 Oct 29. PMID: 39467290 https://www.acpjournals.org/doi/10.7326/M24-0178
  20. http://www.crestor.com

Component-of

ezetimibe/rosuvastatin (Roszet)