Crestor

Generic Name: Rosuvastatin Calcium
Class: HMG-CoA Reductase Inhibitors
VA Class: CV350
Chemical Name: 7 - [4 - (4 - fluorophenyl) - 6 - (1 - methylethyl) - 2 - [methylsulfonyl)amino] - 5 - pyrimi - dinyl] - 3,5 - dihydroxy - 6 - heptenoic acid calcium
Molecular Formula: 2C₂₂H₂₇FN₃O₆S•Ca
CAS Number: 147098-20-2

Special Alerts:

[Posted 09/30/2008] An FDA analysis provides new evidence that the use of statins does not increase incidence of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease often referred to as “Lou Gehrig's Disease.” The FDA analysis, undertaken after the agency received a higher than expected number of reports of ALS in patients on statins, is based on data from 41 long-term controlled clinical trials. The results showed no increased incidence of the disease in patients treated with a statin compared with placebo.

The FDA is anticipating the completion of a case-control or epidemiological study of ALS and statin use. Results from this study should be available within 6-9 months. FDA is also examining the feasibility of conducting additional epidemiologic studies to examine the incidence and clinical course of ALS in patients taking statins.

Based on currently available information, health care professionals should not change their prescribing practices for statins and patients should not change their use of statins. For more information visit the FDA website at: and .

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).¹

Uses for Crestor

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Dyslipidemias

Adjunct to dietary therapy in adults to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), non-HDL-cholesterol, and triglyceride concentrations and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.¹

Reduction of elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available.¹

Adjunct to dietary therapy in the management of patients with elevated serum triglyceride concentrations.¹

Produces greater reductions in LDL-cholesterol concentrations than atorvastatin, pravastatin, or simvastatin on a mg-for-mg basis.¹

Crestor Dosage and Administration

General

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  Patients should be placed on a standard lipid-lowering diet before initiation of rosuvastatin therapy and should remain on this diet during treatment with the drug.^{1 7}

  
  

Administration

Oral Administration

Administer orally at any time of day without regard to meals.¹

If used with cyclosporine or gemfibrozil, adjustment in the treatment regimen recommended.¹ (See Specific Drugs under Interactions.)

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as rosuvastatin calcium; dosage expressed in terms of rosuvastatin.¹

When initiating statin therapy or switching from another statin, select appropriate initial dosage, then carefully adjust dosage according to individual requirements and response.¹

Adults

Dyslipidemias

Primary Hypercholesterolemia and Mixed Dyslipidemia

Oral

Usual initial dosage is 10 mg once daily.¹ Initiate at 5 mg once daily in patients requiring less aggressive LDL-cholesterol reductions, patients with predisposing factors for myopathy, or patients at risk of increased exposure to rosuvastatin (e.g., Asian patients, patients receiving concomitant cyclosporine therapy, patients with severe renal impairment).¹ (See Special Populations under Dosage and Administration and see Specific Drugs under Interactions.)¹ Initiate at 20 mg once daily in patients with marked hypercholesterolemia (LDL-cholesterol >190 mg/dL) and aggressive lipid targets.¹

Determine serum lipoprotein concentrations within 2–4 weeks after initiating and/or titrating therapy and adjust dosage accordingly.¹ Usual maintenance dosage is 5–40 mg once daily.¹

Reserve 40-mg daily dosage for patients who have not achieved their LDL-cholesterol goal with the 20-mg daily dosage.¹

Homozygous Familial Hypercholesterolemia

Oral

Initially, 20 mg once daily.¹ Dosage can be increased up to 40 mg once daily.¹

Hypertriglyceridemia

Oral

Initially, 10 mg once daily.¹¹ Usual maintenance dosage is 5–40 mg once daily.¹¹

Prescribing Limits

Adults

Dyslipidemias

Oral

Maximum 40 mg once daily.¹

Special Populations

Asian Patients

Initially, 5 mg once daily.¹ When contemplating dosage escalation in patients experiencing inadequate response with 5, 10, or 20 mg daily, consider potential for increased systemic exposure in Asian patients relative to Caucasian patients.¹ (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage modification not necessary in patients with mild to moderate renal impairment.¹

Patients with severe renal impairment (Cl_cr <30 mL/minute) not undergoing hemodialysis: Initially, 5 mg once daily; dosage can be increased up to 10 mg once daily.¹

Cautions for Crestor

Contraindications

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  Active liver disease or unexplained, persistent elevations of serum aminotransferases.¹

  
  


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  Pregnancy or lactation.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


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  Known hypersensitivity to rosuvastatin or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Fetal/Neonatal Morbidity and Mortality

Suppression of cholesterol biosynthesis could cause fetal harm.¹ Congenital anomalies following intrauterine exposure to statins reported rarely.

Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.¹ If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.¹

Hepatic Effects

Associated with increases in serum aminotransferase (AST, ALT) concentrations.¹

Pancreatitis, hepatitis, jaundice, increased serum alkaline phosphatase concentrations, increased γ-glutamyl transpeptidase concentrations, and increased bilirubin concentrations reported.¹ Fatty change in liver and rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma reported with other statins.

Perform liver function tests before and at 12 weeks after initiation of therapy or any increase in dosage and periodically (e.g., semiannually) thereafter.¹

Patients who develop increased serum AST/ALT concentrations or manifestations of liver disease should receive frequent liver function tests thereafter until the abnormalities return to normal.¹ If increases in AST or ALT concentrations of >3 times the ULN persist, reduce dosage or discontinue therapy.¹

Musculoskeletal Effects

Myopathy (manifested as muscle pain, tenderness, or weakness and serum CK concentration increases >10 times the ULN) reported occasionally.¹

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in S_cr [usually accompanied by brown urine and urinary myoglobinuria]) reported rarely.¹ Rhabdomyolysis occurs more frequently with 40-mg daily dosage compared with lower dosages.¹ However, risk of rhabdomyolysis is similar between rosuvastatin and other statins.¹² In clinical studies, incidence of myopathy and rhabdomyolysis increased with dosages >40 mg daily.¹

Risk of myopathy increased in patients receiving higher doses of statins; in patients with multisystem disease (e.g., renal or hepatic impairment); in patients with concurrent serious infections or hypothyroidism; in patients (particularly women) of advanced age (≥65 years of age); in patients at risk of increased exposure to rosuvastatin (e.g., Asian patients); in patients with small body frame and frailty; and in patients undergoing surgery (i.e., during perioperative periods).¹ Risk also may be increased by concomitant administration of cyclosporine, niacin, or fibric acid derivatives (e.g., gemfibrozil).¹

Measure baseline serum CK concentrations prior to initiation of therapy, particularly in black men and patients receiving concomitant therapy with fibric acid derivatives.

Obtain serum CK concentrations and compare with baseline concentrations in patients presenting with musculoskeletal symptoms suggestive of myopathy; because hypothyroidism may be a predisposing factor, TSH concentrations also should be obtained in such patients.

Discontinue if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected.¹

Monitor patients weekly if myalgia (muscle pain, tenderness) is present with either no CK elevation or a moderate elevation (3–10 times the ULN) until manifestations improve; discontinue if manifestations worsen.

Dosage reduction or temporary discontinuance may be prudent in patients with muscle discomfort and/or weakness in the presence of progressive elevation of CK concentrations on serial measurements.

Temporarily withhold or discontinue therapy in any patient experiencing an acute or serious condition suggestive of a myopathy.¹

Temporarily withhold or discontinue therapy in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).¹

Sensitivity Reactions

Hypersensitivity Reactions

Face edema, vesiculobullous rash, urticaria, and angioedema reported.¹

General Precautions

Role as Adjunct Therapy

Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.¹

CNS Effects

CNS vascular lesions (e.g., perivascular hemorrhages and edema, mononuclear cell infiltration of perivascular spaces) observed in animals receiving other statins.¹

Ocular Effects

Optic nerve degeneration observed in animals receiving other statins.¹

Specific Populations

Pregnancy

Category X.¹ (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Discontinue nursing or the drug. (See Contraindications under Cautions.)

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.¹

Caution in patients (particularly women) of advanced age (≥65 years of age) and in those with small body frame and frailty.

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.¹ (See Contraindications under Cautions.)

Renal Impairment

Dosage adjustments necessary in patients with severe renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Myalgia, constipation, asthenia, abdominal pain, nausea.¹

Interactions for Crestor

Minimally metabolized by CYP2C9.¹

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum- and magnesium hydroxide-containing)	Decreased absorption of rosuvastatin1	Administer antacid at least 2 hours after rosuvastatin1
Anticoagulants, oral (e.g., warfarin)	Increased INR1	Closely monitor PT until stabilized if rosuvastatin is initiated or dosage is adjusted in patients receiving a coumarin anticoagulant.1 Thereafter, monitor PT at intervals usually recommended for patients receiving coumarin anticoagulants1
Antifungals, azoles	Fluconazole: Increased rosuvastatin concentrations1 Ketoconazole: Pharmacokinetic interaction unlikely1 Itraconazole: Increased rosuvastatin concentrations1	Fluconazole: Pharmacokinetic interaction not considered clinically important1 Itraconazole: Pharmacokinetic interaction not considered clinically important1
Bile acid sequestrants	Enhanced effect on total and LDL-cholesterol1
Cyclosporine	Increased rosuvastatin concentrations1 Increased risk of myopathy1	If used concomitantly, rosuvastatin dosage should not exceed 5 mg daily1
Digoxin	Pharmacokinetic interaction unlikely1
Erythromycin	Decreased rosuvastatin concentrations1	Not considered clinically important1
Fibric acid derivatives (fenofibrate, gemfibrozil)	Increased risk of myopathy and/or rhabdomyolysis1 Gemfibrozil: Increased rosuvastatin concentrations1 Fenofibrate: Pharmacokinetic interaction unlikely1	Gemfibrozil: Concomitant use generally should be avoided1 If used concomitantly with gemfibrozil, rosuvastatin dosage should not exceed 10 mg daily1
Niacin	Increased risk of myopathy and/or rhabdomyolysis1	Weigh benefits against potential risks1
Oral contraceptives	Increased concentrations of ethinyl estradiol and norgestrel1

Crestor Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 20%.¹

Peak plasma concentrations attained within 3–5 hours.¹

Onset

Maximal response occurs within 4 weeks.¹

Duration

Response maintained during continued therapy.¹

Food

Food decreases rate but not extent of absorption.¹

Special Populations

Race: Clinically important differences in pharmacokinetics among white, Hispanic, African American, or Afro-Caribbean groups not demonstrated.¹ Compared with Caucasian patients residing in the US, rosuvastatin concentrations are higher in Asian patients (of Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian ancestry).¹ (See Asian Patients under Dosage and Administration.)

Patients with severe renal impairment (Cl_cr <30 mL/minute) and those undergoing chronic hemodialysis: Rosuvastatin plasma concentrations increased 3-fold.¹

Patients with mild to moderate renal impairment (Cl_cr ≥30 mL/minute): Plasma concentrations not altered.¹

Patients with hepatic impairment (Child-Pugh class A and B, chronic alcohol-induced liver disease): Plasma concentrations increased.¹

Distribution

Extent

Crosses the placenta.¹ Distributed into milk in rats; not known whether distributed into human milk.¹

Plasma Protein Binding

88% (mainly albumin).¹

Elimination

Metabolism

Not extensively metabolized; only 10% of dose is recovered as metabolite.¹

Metabolized by CYP2C9 to active metabolite.¹

Elimination Route

Excreted principally in feces (90%) as unchanged drug and metabolites.¹

Half-life

Approximately 19 hours.¹

Stability

Storage

Oral

Tablets

20–25°C.¹ Protect from moisture.¹

ActionsActions

• 
  

  Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.^{1 2} Reduces serum concentrations of total cholesterol, LDL-cholesterol, VLDL-cholesterol, non-HDL-cholesterol, apo B, and triglycerides; increases HDL-cholesterol concentrations.¹

  
  


• 
  

  Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries, modulate BP in hypercholesterolemic patients with hypertension, and possess anti-inflammatory activity.

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of informing patients about risks, especially rhabdomyolysis, associated with statins alone or combined with other drugs.¹ Importance of patients promptly reporting muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever,¹ brown urine, and flu-like symptoms.

  
  


• 
  

  Importance of adhering to nondrug therapies and measures, including dietary management, weight control, physical activity, and management of potentially contributory disease (e.g., diabetes mellitus).

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹ Necessity for clinicians to advise women to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) during therapy and to advise pregnant women of risk to the fetus.¹

  
  


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  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

  
  


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  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Rosuvastatin Calcium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg (of rosuvastatin)	Crestor	AstraZeneca
		10 mg (of rosuvastatin)	Crestor	AstraZeneca
		20 mg (of rosuvastatin)	Crestor	AstraZeneca
		40 mg (of rosuvastatin)	Crestor	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Crestor 10MG Tablets (ASTRAZENECA): 30/$154.99 or 90/$426.96

Crestor 20MG Tablets (ASTRAZENECA): 30/$155.98 or 90/$427.99

Crestor 40MG Tablets (ASTRAZENECA): 30/$156.99 or 90/$427.95

Crestor 5MG Tablets (ASTRAZENECA): 30/$154.99 or 90/$426.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. AstraZeneca Pharmaceuticals. Crestor (rosuvastatin calcium) tablets prescribing information. Wilmington, DE. 2005 Mar.

2. Davidson M, Ma P, Stein EA. Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. Am J Cardiol. 2003; 89:268-75.

3. Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR trial). Am J Cardiol. 2003; 92:152-60. [IDIS 502119] [PubMed 12860216]

4. Schneck DW, Knopp RH, Ballantyne CM. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol. 2003; 91:33-41. [IDIS 491642] [PubMed 12505568]

5. Capuzzi DM, Morgan JM, Weiss RJ. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003; 91:1304-10. [IDIS 500482] [PubMed 12767421]

6. Carswell CI, Plosker GL, Jarvis B. Rosuvastatin. Drugs. 2002; 62:2075-85.

7. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site.

8. Pasternak RC, Smith SC Jr, Bairey-Merz CN et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute. Circulation. 2002;106:1024-8.

9. Anon. Bayer voluntarily withdraws Baycol. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2001 Aug 8.

10. Pasternak RC, Smith SC Jr, Bairey-Merz CN et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute. Circulation. 2002;106:1024-8.

11. AstraZeneca, Wilmington, DE: Personal communication.

12. Anon. Rosuvastatin (marketed as Crestor). FDA Alert for Healthcare Professionals. Rockville, MD. From FDA website; accessed 2005 Mar 2.

More Crestor resources

• Crestor Side Effects (in more detail)
• Crestor Dosage
• Crestor Use in Pregnancy & Breastfeeding
• Drug Images
• Crestor Drug Interactions
• Crestor Support Group
• 39 Reviews for Crestor - Add your own review/rating

• Crestor Prescribing Information (FDA)


• Crestor Advanced Consumer (Micromedex) - Includes Dosage Information


• Crestor MedFacts Consumer Leaflet (Wolters Kluwer)


• Crestor Consumer Overview

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