Pharmacokinetics

  • Absorption: In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both Cmax and Area Under the Curve increased in approximate proportion to CRESTOR® (rosuvastatin) dose. The absolute bioavailability of rosuvastatin is approximately 20%. Administration of CRESTOR with food did not affect the Area Under the Curve of rosuvastatin. The Area Under the Curve of rosuvastatin does not differ following evening or morning drug administration[1a]

  • Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations[1b]

  • Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of the parent compound. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound[1c]

  • Excretion: Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). The elimination half-life (t1/2) of rosuvastatin is approximately 19 hours. After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route[1d]

  • Race: A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among Caucasian, Hispanic, and Black or Afro-Caribbean groups. However, pharmacokinetic studies, including one conducted in the U.S. have demonstrated an approximate 2-fold elevation in median exposure (Area Under the Curve and Cmax) in Asian subjects when compared with a Caucasian control group[1e]

  • Gender: There were no differences in plasma concentrations of rosuvastatin between men and women[1f]

  • Geriatric: There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥65 years)[1g]

  • Renal Impairment: Mild to moderate renal impairment (CLcr ≥30 mL/min/1.73 m2) had no influence on plasma concentrations of rosuvastatin. However, plasma concentrations of rosuvastatin increased to a clinically significant extent (about 3-fold) in patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) not receiving hemodialysis compared with healthy subjects (CLcr >80 mL/min/1.73 m2)[1h]

  • Hemodialysis: Steady-state plasma concentrations of rosuvastatin in patients on chronic hemodialysis were approximately 50% greater compared with healthy volunteer subjects with normal renal function[1i]

  • Hepatic Impairment: In patients with chronic alcohol liver disease, plasma concentrations of rosuvastatin were modestly increased. In patients with Child-Pugh A disease, Cmax and Area Under the Curve were increased by 60% and 5%, respectively, as compared with patients with normal liver function. In patients with Child-Pugh B disease, Cmax and Area Under the Curve were increased 100% and 21%, respectively, compared with patients with normal liver function[1j]

  • Enasidenib increased rosuvastatin exposure more than 2.4-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. In patients taking enasidenib, do not exceed a dose of CRESTOR 10 mg once daily

Drug-Drug Interactions

  • Cytochrome P450 3A4: Rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent[1k]

  • Cyclosporine: Combination increases rosuvastatin exposure. The dose of CRESTOR should not exceed 5 mg once daily[1l]

  • Teriflunomide: Combination increases rosuvastatin exposure. If used together, the dose of CRESTOR should not exceed 10 mg once daily

  • Enasidenib: Combination increases rosuvastatin exposure. If used together, the dose of CRESTOR should not exceed 10 mg once daily

  • Capmatinib: Combination increases rosuvastatin exposure. If used together, the dose of CRESTOR should not exceed 10 mg once daily

  • Fostamatinib: Combination increases rosuvastatin exposure. If used together, the dose of CRESTOR should not exceed 20 mg once daily

  • Febuxostat: Combination increases rosuvastatin exposure. If used together, the dose of CRESTOR should not exceed 20 mg once daily

  • Gemfibrozil: Combination should be avoided. If used together, the dose of CRESTOR should be initiated at 5 mg once daily and should not exceed 10 mg once daily[1m]

  • Tafamidis: Combination increases rosuvastatin exposure. Avoid concomitant use. If used together, initiate CRESTOR at the 5 mg dose once daily. The dose of CRESTOR should not exceed 20 mg once daily. Caution should be exercised when prescribing CRESTOR with tafamidis

  • Anti-viral Medications: The combination of sofosbuvir/velpatasvir/voxilaprevir which are anti-Hepatitis C virus (anti-HCV) drugs, increases rosuvastatin exposure. Similarly, the combination of ledipasvir/sofosbuvir may significantly increase rosuvastatin exposure. For these combinations of anti-HCV drugs, concomitant use with CRESTOR is not recommended.

    Simeprevir and combinations of dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir which are anti-HCV drugs increase rosuvastatin exposure. Combinations of atazanavir/ritonavir and lopinavir/ritonavir, which are anti-HIV-1 drugs, increase rosuvastatin exposure. For these anti-viral drugs, the dose of CRESTOR should be initiated at 5 mg once daily and should not exceed 10 mg once daily

    The combinations of fosamprenavir/ritonavir or tipranavir/ritonavir, which are anti-HIV-1 drugs, produce little or no change in rosuvastatin exposure. No dose adjustment is needed for concomitant use with these combinations

  • Darolutamide increased rosuvastatin exposure more than 5 fold. Therefore, in patients taking darolutamide, the dose of CRESTOR should not exceed 5 mg once daily

  • Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy. If used together, the dose of CRESTOR should not exceed 10 mg once daily

  • Coumarin anticoagulants: Combination prolongs INR. Achieve stable INR prior to starting CRESTOR. Monitor INR frequently until stable upon initiation or alteration of CRESTOR therapy[1n]

  • Concomitant lipid-lowering therapies: Use with fibrates or lipid-modifying doses (≥1 g/day) of niacin increases the risk of adverse skeletal muscle effects. Caution should be used when prescribing with CRESTOR[1o]

  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with statins, including CRESTOR, coadministered with colchicine, and caution should be exercised when prescribing CRESTOR with colchicine[1p]

  • Concomitant use of CRESTOR and ticagrelor has been shown to increase rosuvastatin concentrations, which may result in increased risk of myopathy. Cases of myopathy and rhabdomyolysis have been reported in patients using both products concomitantly. Cases have occurred more frequently in patients taking 40 mg of rosuvastatin. In patients taking concomitant ticagrelor, especially those with additional risk factors for myopathy and rhabdomyolysis, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of CRESTOR[1q]

  • Concomitant use of antacids: When taking CRESTOR with an aluminum and magnesium hydroxide combination antacid, the antacid should be taken at least 2 hours after CRESTOR administration[1r]

Next: Side Effects

SAVINGS ELIGIBILITY

Eligible patients MAY pay as low as $3 for a 30-, 60-, or 90-day supply.[*]

* ^ Subject to eligibility. Restrictions apply.

Learn About Savings Eligibility

HELP YOUR PATIENTS REACH LDL-C GOAL WITH CRESTOR

In the STELLAR trial, in patients with hyperlipidemia or mixed dyslipidemia, nearly 9 out of 10 met their LDL-C goal with CRESTOR 20 mg.

Learn about patients reaching LDL-C goal

Important Safety Information for CRESTOR® (rosuvastatin) Tablets

  • CRESTOR is contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels or a known hypersensitivity to any component of this product
  • Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with statins, including CRESTOR. These risks can occur at any dose level, but are increased at the highest dose (40 mg)
  • CRESTOR should be prescribed with caution in patients with predisposing factors for myopathy (eg, age ≥65 years, inadequately treated hypothyroidism, renal impairment). The risk of myopathy during treatment with CRESTOR may be increased in Asian patients and with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), cyclosporine, teriflunomide, enasidenib, capmatinib, fostamatinib, febuxostat, gemfibrozil, tafamidis, darolutamide, regorafenib, atazanavir/ritonavir, lopinavir/ritonavir, simeprevir or combination of sofosbuvir/velpatasvir/voxilaprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, all combinations with ledipasvir (including ledipasvir/sofosbuvir), colchicine or ticagrelor
  • Therapy with CRESTOR should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, and if muscle signs and symptoms persist after discontinuing CRESTOR
  • There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Treatment with immunosuppressive agents may be required. Discontinue CRESTOR if IMNM is suspected
  • Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue CRESTOR
  • CRESTOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease
  • CRESTOR significantly increased INR in patients receiving coumarin anticoagulants (eg, warfarin). In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs
  • Dipstick-positive proteinuria and microscopic hematuria were observed among patients treated with CRESTOR. These findings were more frequent in patients taking CRESTOR 40 mg, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, dose reduction should be considered for patients on CRESTOR therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing
  • Increases in HbA1c and fasting serum glucose levels have been reported with statins, including CRESTOR. Based on clinical trial data with CRESTOR, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus
  • In the controlled clinical trials database, the most common adverse reactions were headache (3.7%), myalgia (3.1%), abdominal pain (2.6%), asthenia (2.5%), and nausea (2.2%)
  • Rare post-marketing reports of cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with statin use, including CRESTOR. These reports are generally nonserious and reversible upon statin discontinuation
  • Discontinue CRESTOR when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient
  • CRESTOR 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg
  • Administer CRESTOR at least 2 hours before aluminum and magnesium hydroxide combination antacids

INDICATIONS

  • To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor
  • Adjunct to diet to:
    • reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia
    • reduce LDL-C and slow the progression of atherosclerosis in adults
    • reduce LDL-C in patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH)
  • Adjunct to other LDL-C lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH)
  • Adjunct to diet for the treatment of adults with primary dysbetalipoproteinemia or hypertriglyceridemia

Read full Prescribing Information.

You may report side effects related to AstraZeneca products.

References:

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  • 1a 1b 1c 1c 1d CRESTOR® (rosuvastatin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
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  • ^ Lipitor® (atorvastatin) [package insert]. New York, New York: Pfizer, 2021
  • ^ Livalo® (pitavastatin) [package insert]. Montgomery, AL: Kowa group of companies, 2020.
  • ^ Zocor® (simvastatin) [package insert]. Jersey City, NJ: Organon & Company, 2022
  • ^ Vytorin® (ezetimibe/simvastatin) [package insert]. Jersey City, NJ: Organon & Company, 2022.
  • ^ Lexcol® (fluvastatin sodium) [package insert]. East Hanover, New Jersey: Novartis; 2020
  • ^ Mevacor® (lovastatin) [package insert]. Whitehouse Station, New Jersey: Merck & Company, Inc. 2012
  • ^ Pravachol® (pravastatin) [package insert]. Princeton, New Jersey: Bristol-Myers Squibb Company, 2020.
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  • ^ Zocor® (simvastatin) [package insert]. Jersey City, NJ: Organon & Company, 2022
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1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k 1l 1m 1n 1o 1p 1q 1r CRESTOR® (rosuvastatin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

1a 1b 1c 1d1d CRESTOR® (rosuvastatin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

  • 1a CRESTOR® (rosuvastatin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
  • 2a Lipitor® (atorvastatin calcium) [prescribing information]. Morgantown, WV: Viatris Specialty LLC, 2024.
  • 3a Faergeman O, Hill L, Windler E, et al; on behalf of the ECLIPSE Study Investigators. Efficacy and tolerability of rosuvastatin and atorvastatin when force-titrated in patients with primary hypercholesterolemia. Cardiology. 2008;111(4):219-228.
  • 4a Jones PH, Davidson MH, Stein EA, et al; for the STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003;92:152-160.
  • 5a Crouse JR 3rd, Raichlen JS, Riley WA, et al; METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297(12):1344-1353.

Lipitor is a registered trademark of Upjohn Manufacturing Ireland Unlimited Company, a Viatris Company.

1a 1b 1c 1d CRESTOR® (rosuvastatin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

This product information is intended for US Health Care Professionals only.

IMPORTANT SAFETY INFORMATION FOR CRESTOR® (ROSUVASTATIN) TABLETS

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