Crestor
(rosuvastatin calcium)Dosage & Administration
Take orally with or without food, at any time of day.
Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating CRESTOR, and adjust dosage if necessary.
Adults: Recommended dosage range is 5 to 40 mg once daily.
Pediatric Patients with HeFH: Recommended dosage range is 5 to 10 mg once daily for patients aged 8 to less than 10 years of age, and 5 to 20 mg once daily for patients aged 10 years and older.
Pediatric Patients with HoFH: Recommended dosage is 20 mg once daily for patients aged 7 years and older.
Asian Patients: Initiate at 5 mg once daily. Consider risks and benefits of treatment if not adequately controlled at doses up to 20 mg once daily.
Patients with Severe Renal Impairment (not on hemodialysis): Initiate at 5 mg once daily; do not exceed 10 mg once daily.
See full prescribing information for CRESTOR dosage and administration modifications due to drug interactions.
By using PrescriberAI, you agree to the AI Terms of Use.
Crestor Prescribing Information
CRESTOR is indicated:
- •
- To reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in adults without established coronary heart disease who are at increased risk of cardiovascular (CV) disease based on age, hsCRP ≥2 mg/L, and at least one additional CV risk factor.
- •
- As an adjunct to diet to:
- ∘
- Reduce LDL-C in adults with primary hyperlipidemia.
- ∘
- Reduce low-density lipoprotein cholesterol (LDL-C) and slow the progression of atherosclerosis in adults.
- ∘
- Reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).
- •
- As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH).
- •
- As an adjunct to diet for the treatment of adults with:
- ∘
- Primary dysbetalipoproteinemia.
- ∘
- Hypertriglyceridemia.
General Dosage and Administration Information
- •
- Administer CRESTOR orally as a single dose at any time of day, with or without food. The tablet should be swallowed whole.
- •
- Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating CRESTOR, and adjust the dosage if necessary.
- •
- If a dose is missed, advise patients not take an extra dose. Resume treatment with the next dose.
Recommended Dosage in Adult Patients
- •
- The dosage range for CRESTOR is 5 to 40 mg orally once daily.
- •
- The recommended dose of CRESTOR depends on a patient’s indication for usage, LDL-C, and individual risk for cardiovascular events.
Recommended Dosage in Pediatric Patients
Dosage in Pediatric Patients 8 Years of Age and Older with HeFH
The recommended dosage range is 5 mg to 10 mg orally once daily in patients aged 8 years to less than 10 years and 5 mg to 20 mg orally once daily in patients aged 10 years and older.
Dosage in Pediatric Patients 7 Years of Age and Older with HoFH
The recommended dosage is 20 mg orally once daily.
Dosing in Asian Patients
Initiate CRESTOR at 5 mg once daily due to increased rosuvastatin plasma concentrations. Consider the risks and benefits of CRESTOR when treating Asian patients not adequately controlled at doses up to 20 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.3)].
Recommended Dosage in Patients with Renal Impairment
In patients with severe renal impairment (CLcr less than 30 mL/min/1.73 m2) not on hemodialysis, the recommended starting dosage is 5 mg once daily and should not exceed 10 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].
There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.
Dosage and Administration Modifications Due to Drug Interactions
CRESTOR Dosage Modifications Due to Drug Interactions
Table 1 displays dosage modifications for CRESTOR due to drug interactions [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].
Concomitantly Used Drug | CRESTOR Dosage Modifications |
Cyclosporine | Do not exceed 5 mg once daily. |
Teriflunomide | Do not exceed 10 mg once daily. |
Enasidenib | Do not exceed 10 mg once daily. |
Capmatinib | Do not exceed 10 mg once daily. |
Fostamatinib | Do not exceed 20 mg once daily. |
Febuxostat | Do not exceed 20 mg once daily. |
Gemfibrozil | Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily. |
Tafamidis | Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 20 mg once daily. |
Antiviral Medications | |
| Concomitant use not recommended. |
| Initiate at 5 mg once daily. Do not exceed 10 mg once daily. |
Darolutamide | Do not exceed 5 mg once daily. |
Regorafenib | Do not exceed 10 mg once daily. |
CRESTOR Administration Modifications Due to Drug Interactions
When taking CRESTOR with an aluminum and magnesium hydroxide combination antacid, administer CRESTOR at least 2 hours before the antacid [see Drug Interactions (7.2)].
CRESTOR tablets:
- •
- 5 mg of rosuvastatin: yellow, round, biconvex, coated tablets. Debossed “CRESTOR” and “5” on one side of the tablet.
- •
- 10 mg of rosuvastatin: pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “10” on one side of the tablet.
- •
- 20 mg of rosuvastatin: pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “20” on one side of the tablet.
- •
- 40 mg of rosuvastatin: pink, oval, biconvex, coated tablets. Debossed “CRESTOR” on one side and “40” on the other side of the tablet.
Pregnancy
Risk Summary
Discontinue CRESTOR when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient.
CRESTOR decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, CRESTOR may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients.
Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with CRESTOR use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data).
In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (MRHD) of 40 mg/day, based on AUC and body surface area (mg/m2), respectively (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Human Data
A Medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score‑based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.
Animal Data
In female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the MRHD dose of 40 mg/day based on AUC).
In pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the MRHD of 40 mg/day based body surface area).
In pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area).
Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. In rabbits, fetal tissue distribution was 25% of maternal plasma concentration after a single oral gavage dose of 1 mg/kg on gestation day 18.
Lactation
Risk Summary
Limited data from case reports in published literature indicate that CRESTOR is present in human milk. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Statins, including CRESTOR, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant.
Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with CRESTOR [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.1)].
Pediatric Use
The safety and effectiveness of CRESTOR as an adjunct to diet to reduce LDL-C have been established in pediatric patients 8 years of age and older with HeFH. Use of CRESTOR for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with HeFH and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with HeFH [see Clinical Studies (14)]. In the 1-year trial with a 12-week controlled phase, there was no detectable effect of CRESTOR on growth, weight, BMI (body mass index), or sexual maturation in patients aged 10 to 17 years.
The safety and effectiveness of CRESTOR as an adjunct to other LDL-C-lowering therapies to reduce LDL-C have been established pediatric patients 7 years of age and older with HoFH. Use of CRESTOR for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with HoFH [see Clinical Studies (14)].
The safety and effectiveness of CRESTOR have not been established in pediatric patients younger than 8 years of age with HeFH, younger than 7 years of age with HoFH, or in pediatric patients with other types of hyperlipidemia (other than HeFH or HoFH).
Geriatric Use
Of the total number of CRESTOR-treated patients in clinical studies, 3159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
Advanced age (≥65 years) is a risk factor for CRESTOR-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving CRESTOR for the increased risk of myopathy [see Warnings and Precautions (5.1)].
Renal Impairment
Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥30 mL/min/1.73 m2). Exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) who are not receiving hemodialysis [see Clinical Pharmacology (12.3)].
Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. In patients with severe renal impairment not on hemodialysis, the recommended starting dosage is 5 mg daily and should not exceed 10 mg daily [see Dosage and Administration (2.5) and Warnings and Precautions (5.1)].
Hepatic Impairment
CRESTOR is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Contraindications (4), Warning and Precautions (5.3) and Clinical Pharmacology (12.3)].
Asian Patients
Pharmacokinetic studies have demonstrated an approximate 2‑fold increase in median exposure to rosuvastatin in Asian subjects when compared with White controls. Adjust the CRESTOR dosage in Asian patients [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].
CRESTOR is contraindicated in the following conditions:
- •
- Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3)].
- •
- Hypersensitivity to rosuvastatin or any excipients in CRESTOR. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with CRESTOR [see Adverse Reactions (6.1)].
Myopathy and Rhabdomyolysis
CRESTOR may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including CRESTOR.
Risk Factors for Myopathy
Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher CRESTOR dosage. Asian patients on CRESTOR may be at higher risk for myopathy [see Drug Interactions (7.1) and Use in Specific Populations (8.8)]. The myopathy risk is greater in patients taking CRESTOR 40 mg daily compared with lower CRESTOR dosages.
Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis
The concomitant use of CRESTOR with cyclosporine or gemfibrozil is not recommended. CRESTOR dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [see Dosage and Administration (2.6)]. Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions (7.1)].
Discontinue CRESTOR if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if CRESTOR is discontinued. Temporarily discontinue CRESTOR in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).
Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the CRESTOR dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Immune-Mediated Necrotizing Myopathy
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue CRESTOR if IMNM is suspected.
Hepatic Dysfunction
Increases in serum transaminases have been reported with use of CRESTOR [see Adverse Reactions (6.1)]. In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to more than three times the ULN occurred in 1.1% of patients taking CRESTOR versus 0.5% of patients treated with placebo. Marked persistent increases of hepatic transaminases have also occurred with CRESTOR. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including CRESTOR.
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)].
Consider liver enzyme testing before CRESTOR initiation and when clinically indicated thereafter. CRESTOR is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)]. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue CRESTOR.
5.4 Proteinuria and Hematuria
In the CRESTOR clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among CRESTOR treated patients. These findings were more frequent in patients taking CRESTOR 40 mg, when compared to lower doses of CRESTOR or comparator statins, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, consider a dose reduction for patients on CRESTOR therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.
Increases in HbA1c and Fasting Serum Glucose Levels
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 [see Adverse Reactions (6.1)]. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.