Safety and Tolerability

Warnings and Precautions

Skeletal Muscle Effects. Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including CRESTOR® (rosuvastatin calcium). 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 with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, atazanavir/ritonavir, or simeprevir. 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.

CRESTOR therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. CRESTOR therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).

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; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.

All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing CRESTOR.

Liver Enzyme Abnormalities and Monitoring. It is recommended that liver enzyme tests be performed before the initiation of CRESTOR, and if signs or symptoms of liver injury occur.

Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG-CoA reductase inhibitors, including CRESTOR. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to CRESTOR therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials.

In a pooled analysis of placebo-controlled trials, increases in serum transaminases to >3 times the upper limit of normal occurred in 1.1% of patients taking CRESTOR versus 0.5% of patients treated with placebo.

There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with CRESTOR, promptly interrupt therapy. If an alternate etiology is not found, do not restart CRESTOR.

CRESTOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of CRESTOR.

Safety and Side Effects

The most commonly reported adverse reactions (incidence ≥2%) in the CRESTOR controlled clinical trial database of 5,394 patients were1,2

  • Headache: 3.7%
  • Myalgia: 3.1%
  • Abdominal pain: 2.6%
  • Asthenia: 2.5%
  • Nausea: 2.2%

Adverse Reactions* Reported by ≥2% of Patients Treated With CRESTOR and Greater Than Placebo in Placebo-Controlled Trials (% of Patients)1

Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown below. These studies had a treatment duration of up to 12 weeks.1

Chart of adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo.

*Adverse reactions by COSTART preferred term.

Adverse Reactions* Reported by ≥2% of Patients Treated With CRESTOR and Greater Than Placebo in the METEOR Trial (% of Patients)1

Adverse reactions reported in ≥2% of patients and at a rate greater than placebo in the METEOR trial are shown below.1

METEOR Trial Chart

*Adverse reactions by MedDRA preferred term.

Frequency recorded as abnormal laboratory value.

For more information concerning the METEOR trial, visit slowing atherosclerosis progression.

In the JUPITER study, 17,802 participants were treated with CRESTOR 20 mg (n=8901) or placebo (n=8901) for a mean duration of 2 years. A higher percentage of CRESTOR-treated patients versus placebo-treated patients, 6.6% and 6.2%, respectively, discontinued study medication due to an adverse event, irrespective of treatment causality. Myalgia was the most common adverse reaction that led to treatment discontinuation.

In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking CRESTOR (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in CRESTOR-treated patients compared to placebo-treated patients. The number of patients with an HbA1c >6.5% at the end of the trial was significantly higher in CRESTOR-treated versus placebo-treated patients.

Adverse Reactions* in the JUPITER Trial Reported by ≥2% of Patients Treated With CRESTOR and Greater Than Placebo (% of Patients)1

Adverse reactions reported in ≥2% of patients and at a rate greater than or equal to placebo in the JUPITER trial are shown below.1

JUPITER Trial Chart

*Treatment-emergent adverse reactions by MedDRA preferred term.

For more information concerning the JUPITER trial, visit primary prevention of CVD indication.

  • Eligible patients can pay as low as $3 for each prescription of CRESTOR

    Subject to eligibility. Restrictions apply. Click here for eligibility information.

    Learn more

  • 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.3

    View the data

3143524-3097604 Last Updated 7/15

Important Safety Information for CRESTOR Tablets

  • CRESTOR is contraindicated in patients with a known hypersensitivity to any component of this product, in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels, in women who are pregnant or may become pregnant, and in nursing mothers
  • 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 with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, atazanavir/ritonavir, or simeprevir
  • Therapy with CRESTOR should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use. 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
  • It is recommended that liver enzyme tests be performed before the initiation of CRESTOR and if signs or symptoms of liver injury occur. All patients treated with CRESTOR should be advised to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including CRESTOR. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with CRESTOR, promptly interrupt therapy. If an alternate etiology is not found, do not restart 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. 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 postmarketing 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
  • CRESTOR 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg

Important Safety Information from the JUPITER Study

  • A higher percentage of rosuvastatin-treated patients vs placebo-treated patients (6.6% and 6.2%, respectively) discontinued study medication due to an adverse event, irrespective of treatment causality. Myalgia was the most common adverse reaction that led to treatment discontinuation
  • In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) vs patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated patients vs placebo-treated patients
  • The most common adverse reactions reported were myalgia (7.6% vs 6.6%), arthralgia (3.8% vs 3.2%), constipation (3.3% vs 3.0%), and nausea (2.4% vs 2.3%) for CRESTOR vs placebo, respectively

Indications

  • CRESTOR is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, ApoB, non-HDL-C, and triglycerides, and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia, and to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels
  • CRESTOR is indicated to reduce the risk of myocardial infarction, stroke, and arterial revascularization procedures in patients without clinically evident coronary heart disease but with an increased risk of cardiovascular disease (CVD) based on age (men ≥50 and women ≥60), high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and the presence of at least one additional CVD risk factor, such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease

Read full Prescribing Information (PDF - 152k) 

#Prescribing Information for CRESTOR. AstraZeneca Pharmaceuticals LP, Wilmington, DE.

‡‡Data on File, 268255, AstraZeneca Pharmaceuticals LP.

Defined as covered without prior authorization on Commercial, Medicare Part D, and Medicaid formularies. “Patients without prior authorization” means covered lives at Tiers 1 to 7 calculated by Fingertip Formulary® as of March 4, 2015, that do not require additional information to the health plan in order for CRESTOR to be covered. Data include covered lives whose prescriptions may be subject to step-therapy requirements.

References:

  1. Prescribing Information for CRESTOR. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
  2. Data on File, 268255, AstraZeneca Pharmaceuticals LP.
  3. 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.

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