rosuvastatin (Crestor)
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Introduction
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
- active liver disease[17]
- caution giving > 20 mg/day
- chronic renal insufficiency
- hypothyroidism
- elderly (> 65 years of age)
- do NOT exceed 20 mg/day in Japanese or Chinese
- do NOT exceed 10 mg/day in patients with severe renal insufficiency
Dosage
- 10-40 mg PO QD
- start 5 mg QD (Asians, renal insufficiency, hypothyroidism, > 65 years of age)[4]
Dosage adjustment in renal failure
- increased plasma levels (up to 3-fold) observed when creatinine clearance < 30 mL/min
- maximum dose 10 mg QD[4]
Pharmacokinetics
- bioavailability about 20%[14]
- mean volume of distribution 134 liters
- maximum plasma levels reached in 3-5 hours[14]
- not a prodrug, miminal activity of metabolites[14]
- 28% renal clearance; 72% hepatic clearance after IV dose
- 10% metabolized by cyt P450 2C9 (CYP2C9)
- 90% excreted in the feces after oral dose[14]
- 1/2life of 19 hours[14]
- serum levels tend to be twice as high in Asians for a given dose[4]
elimination by hemodialysis = -
Monitor
- liver function tests
- urine protein (at 40 mg dose)
- 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
- hepatotoxicity (rare)
- increased liver function tests 1% (same as other statins)
- proteinuria (only statin associated with proteinuria)
- rosuvastatin is associated with increased risk of hematuria, proteinuria, & ESRD compared wth atorvastatin[16]
- 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]
- myopathy/rhabdomyolysis[3]
- potentially teratogenic
Toxicity:
- drug adverse effects of HMG CoA reductase inhibitors
- drug adverse effects of anti-hyperlipidemic agents
Drug interactions
- limit dose of rosuvastatin to 5 mg QD in combination with cyclosporine, tacrolimus, everolimus, sirolimus
- increased rosuvastatin plasma levels in combination with cyclosporine
- limit dose of rosuvastatin to 10 mg QD in combination with gemfibrozil (increased incidence of myopathy)[4][14]
- oral contraceptives: rosuvastatin increases plasma levels of ethinyl estradiol (26%) & norgestrel (34%)
- close monitoring for myopathy when used in combination with colchicine[14]
- 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]
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of statins with vitamin D
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of statins with influenza virus vaccines
- drug interaction(s) of statins with macrolide
- drug interaction(s) of statins with antiviral protease inhibitors
- drug interaction(s) of statins with fibrates
Mechanism of action
- lowers LDL by 50% (10 mg QD)
- increases HDL 10-14% (most effective statin)
- 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]
More general terms
Additional terms
- A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID)
- Jupiter study
Component of
References
- ↑ Prescriber's Letter 10(8):43 2003
- ↑ Jump up to: 2.0 2.1 Prescriber's Letter 11(4):19-20 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200402&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 3.0 3.1 FDA Medwatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#crestor
- ↑ Jump up to: 4.0 4.1 4.2 4.3 4.4 Prescriber's Letter 12(4): 2005 FDA Public Health Advisory on Crestor (rosuvastatin) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210402&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 5.0 5.1 Prescriber's Letter 12(7): 2005 The Safety of Crestor (Rosuvastatin) - An Update Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210703&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241201&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 17(3): 2010 Rosuvastatin (Crestor) for High C-Reactive Protein (CRP) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260302&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 8.0 8.1 AstraZeneca announces top-line results from SATURN study http://www.astrazeneca.com/Media/Press-releases/Article/02092011-astrazeneca-saturn-study-results
- ↑ Jump up to: 9.0 9.1 Nicholls SJ et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011 Nov 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22085316 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1110874
- ↑ Jump up to: 10.0 10.1 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 - ↑ Jump up to: 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/27144849
- ↑ Jump up to: 12.0 12.1 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ Jump up to: 13.0 13.1 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
- ↑ Jump up to: 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27754879 <Internet> http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf
- ↑ Jump up to: 15.0 15.1 Brailovski E et al Rosuvastatin Myotoxicity After Starting Canagliflozin Treatment: A Case Report. Ann Intern Med. Aug 4, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32744865 https://www.acpjournals.org/doi/10.7326/L20-0549
- ↑ Jump up to: 16.0 16.1 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: https://www.ncbi.nlm.nih.gov/pubmed/35853713 https://jasn.asnjournals.org/content/early/2022/07/19/ASN.2022020135 - ↑ Jump up to: 17.0 17.1 Windle ML Rapid Rx Quiz: Statin Intolerance and Related Concerns Medscape. September 01, 2022 https://reference.medscape.com/viewarticle/979515
- ↑ Jump up to: 18.0 18.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37852649 PMCID: PMC10583134 Free PMC article https://www.bmj.com/content/383/bmj-2023-075837
- ↑ Jump up to: 19.0 19.1 19.2 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: https://www.ncbi.nlm.nih.gov/pubmed/39467290 https://www.acpjournals.org/doi/10.7326/M24-0178
- ↑ http://www.crestor.com