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:

AvPAK

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Pediatric use information for patients 7 to 17 years of age is approved for AstraZeneca’s CRESTOR (rosuvastatin calcium) tablets. However, due to AstraZeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. Rosuvastatin calcium tablets are indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). Rosuvastatin calcium tablets are indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. Rosuvastatin calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias. Rosuvastatin calcium tablets are contraindicated in the following conditions: •Patients with a known hypersensitivity to any component of this product. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin calcium tablets [see Adverse Reactions (6.1)]. •Patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels [see Warnings and Precautions (5.2)]. •Pregnancy [see Use in Specific Populations (8.1, 8.3)]. •Lactation. Limited data indicate that rosuvastatin calcium is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require rosuvastatin calcium tablets treatment should not breastfeed their infants [see Use in Specific Populations (8.2)]. Risk Summary Rosuvastatin calcium tablets are contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit to therapy with rosuvastatin calcium tablets during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, rosuvastatin calcium tablets may cause fetal harm when administered to pregnant women. Rosuvastatin calcium tablets should be discontinued as soon as pregnancy is recognized [ see Contraindications (4)]. Limited published data on the use of rosuvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, there were no adverse developmental effects with oral administration of rosuvastatin during organogenesis at systemic exposures equivalent to a maximum recommended human dose (MRHD) of 40 mg/day in rats or rabbits (based on AUC and body surface area, respectively). In rats and rabbits, decreased pup/fetal survival occurred at 12 times and equivalent, respectively, to the MRHD of 40 mg/day [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 Limited published data on rosuvastatin have not shown an increased risk of major congenital malformations or miscarriage. Rare reports of congenital anomalies have been received following intrauterine exposure to other statins. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a ≥3 to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Animal Data 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. A higher fetal tissue distribution (25% maternal plasma concentration) was observed in rabbits after a single oral gavage dose of 1 mg/kg on gestation day 18. Rosuvastatin administration did not indicate a teratogenic effect in rats at ≤25 mg/kg/day or in rabbits ≤3 mg/kg/day (doses equivalent to the MRHD of 40 mg/day based on AUC and body surface area, respectively). 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). Risk Summary   Rosuvastatin use is contraindicated during breastfeeding [see Contraindications (4)] . Limited data indicate that rosuvastatin calcium 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. Because of the potential for serious adverse reactions in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with rosuvastatin calcium. Contraception Rosuvastatin calcium may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with rosuvastatin calcium. Pediatric use information for patients 7 to 17 years of age is approved for AstraZeneca's CRESTOR (rosuvastatin calcium) tablets. However, due to AstraZeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Of the 10,275 patients in clinical studies with rosuvastatin calcium tablets, 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, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients are at higher risk of myopathy and rosuvastatin calcium tablets should be prescribed with caution in the elderly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)]. 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 and dose adjustment is required [see Dosage and Administration (2.5),Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)]. Rosuvastatin calcium tablets are contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Chronic alcohol liver disease is known to increase rosuvastatin exposure; rosuvastatin calcium tablets should be used with caution in these patients [see Contraindications (4), Warning and Precautions (5.2) 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 Caucasian controls. Rosuvastatin calcium tablets dosage should be adjusted in Asian patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

Product summary:

Rosuvastatin Calcium Tablets are supplied as: 5 mg: Light yellow to yellow, round, bevel edged biconvex film coated tablets debossed with 'H' on one side and 'R3' on the other side. 10 mg: Light pink to pink, round, bevel edged biconvex film coated tablets debossed with 'H' on one side and 'R4' on the other side. They are supplied as follows. NDC 50268-709-15 (10 tablets per card, 5 cards per carton). 20 mg: Light pink to pink, round, bevel edged biconvex film coated tablets debossed with 'H' on one side and 'R5' on the other side. They are supplied as follows. NDC 50268-710-15 (10 tablets per card, 5 cards per carton). 40 mg: Light pink to pink, oval, bevel edged biconvex film coated tablets debossed with 'H' on one side and 'R6' on the other side. They are supplied as follows. NDC 50268-711-15 (10 tablets per card, 5 cards per carton). Dispensed in Unit Dose Package. For Institutional Use Only. Storage Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from moisture.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

ROSUVASTATIN- ROSUVASTATIN TABLET, FILM COATED
AVPAK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
ROSUVASTATIN CALCIUM TABLETS
RX ONLY
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ROSUVASTATIN CALCIUM
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ROSUVASTATIN CALCIUM
TABLETS.
ROSUVASTATIN CALCIUM TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2003
INDICATIONS AND USAGE
Rosuvastatin calcium tablet is an HMG Co-A reductase inhibitor
indicated for:
• adult patients with hypertriglyceridemia as an adjunct to diet
(1.3)
• adult patients with primary dysbetalipoproteinemia (Type III
hyperlipoproteinemia) as an adjunct to diet
(1.4)
• adult patients with homozygous familial hypercholesterolemia
(HoFH) to reduce LDL-C, total-C, and
ApoB (1.5)
Limitations of use (1.8): Rosuvastatin calcium tablets have not been
studied in Fredrickson Type I and V
dyslipidemias.
DOSAGE AND ADMINISTRATION
•Rosuvastatin calcium tablets can be taken with or without food, at
any time of day. (2.1)
•Dose range: 5 to 40 mg once daily. Use 40 mg dose only for patients
not reaching LDL-C goal with 20
mg. (2.1)
•Adult HoFH: Starting dose 20 mg/day (2.1)
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg, 10 mg, 20 mg, and 40 mg (3)
CONTRAINDICATIONS
•Known hypersensitivity to product components (4)
•Active liver disease, which may include unexplained persistent
elevations in hepatic transaminase levels
(4)
•Pregnancy (4, 8.1, 8.3)
•Lactation (4, 8.2)
WARNINGS AND PRECAUTIONS
Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks
increase with use of 40 mg dose,
advanced age (≥65), hypothyroidism, renal impairment, and
combination use with cyclosporine,
atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir. Cases of
myopathy and rhabdomyolysis with acute
renal failure secondary to myoglobinuria have been reported. Advise
patients to promptly report to their
physician unexplained and/or persistent muscle pain, tenderness, or
weakness and dis