CRESTOR- rosuvastatin tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ROSUVASTATIN CALCIUM (UNII: 83MVU38M7Q) (ROSUVASTATIN - UNII:413KH5ZJ73)

Available from:

AstraZeneca Pharmaceuticals LP

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

CRESTOR is indicated: CRESTOR is contraindicated in the following conditions: 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. 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)] . 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). 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)] . 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)] . 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)] . 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)] .

Product summary:

CRESTOR tablets are supplied as: Strength How Supplied NDC Tablet Description 5 mg bottles of 90 tablets 0310-7560-90 Yellow, round, biconvex, coated tablets. Debossed “ZD4522” and “5” on one side 10 mg bottles of 90 tablets 0310-7570-90 Pink, round, biconvex, coated tablets. Debossed “ZD4522” and “10” on one side 20 mg bottles of 90 tablets 0310-7580-90 Pink, round, biconvex, coated tablets. Debossed “ZD4522” and “20” on one side 40 mg bottles of 30 tablets 0310-7590-30 Pink, oval, biconvex, coated tablets. Debossed “ZD4522” on one side and “40” on the other side Storage Store at controlled room temperature, 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Authorization status:

New Drug Application

Summary of Product characteristics

CRESTOR- ROSUVASTATIN CALCIUM TABLET, FILM COATED
ASTRAZENECA PHARMACEUTICALS LP
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CRESTOR SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CRESTOR.
CRESTOR (ROSUVASTATIN) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2003
RECENT MAJOR CHANGES
Dosage and Administration Modifications Due to Drug Interactions (2.6)
07/2023
Contraindications, Pregnancy and Lactation (4) Removed 01/2023
Warnings and Precautions (5.2) 01/2023
Warnings and Precautions, Concomitant Coumarin Anticoagulants (5.4)
Removed 01/2023
INDICATIONS AND USAGE
CRESTOR is an HMG Co‑A reductase inhibitor (statin) indicated: (1)
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DOSAGE AND ADMINISTRATION
Take orally with or without food, at any time of day. (2.1)
Assess LDL-C when clinically appropriate, as early as 4 weeks after
initiating CRESTOR, and adjust dosage
if necessary. (2.1)
_Adults:_ Recommended dosage range is 5 to 40 mg once daily. (2.1)
_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. (2.2)
_Pediatric Patients with HoFH_: Recommended dosage is 20 mg once daily
for patients aged 7 years and
older. (2.2)
_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. (2.4)
_Patients with Severe Renal Impairment (not on hemodialysis)_:
Initiate at 5 mg once daily; do not exceed
10 mg once daily. (2.5, 5.1, 8.6)
See full prescribing information for CRESTOR dosage and administration
modifications due to drug
interactions. (2.6)
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg, 10 mg, 20 mg, and 40 mg of rosuvastatin. (3)
CONTRAINDICATIONS
Acute liver failure or decompensated cirrhosis. (4)
Hypersensitivity to rosuvastatin or any excipients in CRESTOR. (4)
WARNINGS AND PRECAUTIONS
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To reduce the risk of stroke, myocardia