ROSUVASTATIN CALCIUM- rosuvastatin calcium tablet, film coated

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
ROSUVASTATIN CALCIUM (UNII: 83MVU38M7Q) (ROSUVASTATIN - UNII:413KH5ZJ73)
Available from:
Direct_Rx
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. 1.3 Hypertriglyceridemia Rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) Rosuvastatin calcium tablets are indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.5 Adult Patients with Homozygous Familial Hypercholesterolemia 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. 1.8 Limitations of Use Rosuvastatin cal
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. They are supplied as follows. Bottle of 90 Tablets Blister pack of 100 (10×10) Unit dose tablets 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. Bottle of 90 Tablets Blister pack of 100 (10×10) Unit dose tablets 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. Bottle of 90 Tablets Blister pack of 100 (10×10) Unit dose tablets 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. Bottle of 30 Tablets Blister pack of 100 (10×10) Unit dose tablets Storage Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from moisture.
Authorization status:
Abbreviated New Drug Application
Authorization number:
61919-701-90

ROSUVASTATIN CALCIUM- rosuvastatin calcium tablet, film coated

Direct_Rx

----------

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.

1.3 Hypertriglyceridemia

Rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients

with hypertriglyceridemia.

1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)

Rosuvastatin calcium tablets are indicated as an adjunct to diet for the treatment of adult patients with

primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).

1.5 Adult Patients with Homozygous Familial Hypercholesterolemia

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.

1.8 Limitations of Use

Rosuvastatin calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias.

2.1 General Dosing Information

The dose range for rosuvastatin calcium tablets in adults are 5 to 40 mg orally once daily. The usual

starting dose is 10 to 20 mg once daily. The usual starting dose in adult patients with homozygous

familial hypercholesterolemia is 20 mg once daily.

The maximum rosuvastatin calcium tablet dose of 40 mg should be used only for those patients who

have not achieved their LDL-C goal utilizing the 20 mg dose [see Warnings and Precautions (5.1)].

Rosuvastatin calcium tablets can be administered as a single dose at any time of day, with or without

food. The tablet should be swallowed whole.

When initiating rosuvastatin calcium tablets therapy or switching from another HMG-CoA reductase

inhibitor therapy, the appropriate rosuvastatin calcium tablets starting dose should first be utilized, and

only then titrated according to the patient’s response and individualized goal of therapy.

After initiation or upon titration of rosuvastatin calcium tablets, lipid levels should be analyzed within 2

to 4 weeks and the dosage adjusted accordingly.

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.

2.3 Dosing in Asian Patients

In Asian patients, consider initiation of rosuvastatin calcium tablets therapy with 5 mg once daily due to

increased rosuvastatin plasma concentrations. The increased systemic exposure should be taken into

consideration when treating Asian patients not adequately controlled at doses up to 20 mg/day [see Use

in Specific Populations (8.8)and Clinical Pharmacology (12.3)].

2.4 Use with Concomitant Therapy

Patients taking cyclosporine

The dose of rosuvastatin calcium tablets should not exceed 5 mg once daily [see Warnings and

Precautions (5.1), Drug Interactions (7.1)and Clinical Pharmacology (12.3)].

Patients taking gemfibrozil

Avoid concomitant use of rosuvastatin calcium tablets with gemfibrozil. If concomitant use cannot be

avoided, initiate rosuvastatin calcium tablets at 5 mg once daily. The dose of rosuvastatin calcium

tablets should not exceed 10 mg once daily [see Warnings and Precautions (5.1), Drug Interactions

(7.2)and Clinical Pharmacology (12.3)].

Patients taking atazanavir and ritonavir, lopinavir and ritonavir, or simeprevir

Initiate rosuvastatin calcium tablets therapy with 5 mg once daily. The dose of rosuvastatin calcium

tablets should not exceed 10 mg once daily [see Warnings and Precautions (5.1), Drug Interactions (7.3)

and Clinical Pharmacology (12.3)].

2.5 Dosing in Patients with Severe Renal Impairment

For patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) not on hemodialysis, dosing of

rosuvastatin calcium tablets should be started at 5 mg once daily and not exceed 10 mg once daily [see

Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)].

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.

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.

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.

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)].

5.1 Skeletal Muscle Effects

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been

reported with HMG-CoA reductase inhibitors, including rosuvastatin calcium tablets. These risks can

occur at any dose level, but are increased at the highest dose (40 mg).

Rosuvastatin calcium tablets should be prescribed with caution in patients with predisposing factors for

myopathy (e.g., age ≥65 years, inadequately treated hypothyroidism, renal impairment).

The risk of myopathy during treatment with rosuvastatin calcium tablets may be increased with

concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil,

cyclosporine, atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir [see Dosage and Administration

(2)and Drug Interactions (7)]. Cases of myopathy, including rhabdomyolysis, have been reported with

HMG-CoA reductase inhibitors, including rosuvastatin, coadministered with colchicine, and caution

should be exercised when prescribing rosuvastatin calcium tablets with colchicine [see Drug

Interactions (7.7)].

Rosuvastatin calcium tablets therapy should be discontinued if markedly elevated creatine kinase levels

occur or myopathy is diagnosed or suspected. Rosuvastatin calcium tablets 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 (e.g., 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 rosuvastatin calcium tablets.

5.2 Liver Enzyme Abnormalities

It is recommended that liver enzyme tests be performed before the initiation of rosuvastatin calcium

tablets, 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 rosuvastatin calcium tablets. 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 rosuvastatin calcium tablets 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 rosuvastatin calcium tablets 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 rosuvastatin calcium tablets, promptly interrupt therapy. If an

alternate etiology is not found, do not restart rosuvastatin calcium tablets.

Rosuvastatin calcium tablets should be used with caution in patients who consume substantial quantities

of alcohol and/or have a history of chronic liver disease [see Clinical Pharmacology (12.3)]. Active

liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to

the use of rosuvastatin calcium tablets [see Contraindications (4)].

5.3 Concomitant Coumarin Anticoagulants

Caution should be exercised when anticoagulants are given in conjunction with rosuvastatin calcium

tablets because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the

prothrombin time/INR. In patients taking coumarin anticoagulants and rosuvastatin calcium tablets

concomitantly, INR should be determined before starting rosuvastatin calcium tablets and frequently

enough during early therapy to ensure that no significant alteration of INR occurs [see Drug

Interactions (7.4)].

5.4 Proteinuria and Hematuria

In the rosuvastatin calcium tablets clinical trial program, dipstick-positive proteinuria and microscopic

hematuria were observed among rosuvastatin calcium tablets treated patients. These findings were more

frequent in patients taking rosuvastatin calcium tablets 40 mg, when compared to lower doses of

rosuvastatin calcium tablets or comparator HMG-CoA reductase inhibitors, though it was generally

transient and was not associated with worsening renal function. Although the clinical significance of

this finding is unknown, a dose reduction should be considered for patients on rosuvastatin calcium

tablets therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.

5.5 Endocrine Effects

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase

inhibitors, including rosuvastatin calcium tablets. Based on clinical trial data with rosuvastatin calcium

tablets, in some instances these increases may exceed the threshold for the diagnosis of diabetes

mellitus [see Adverse Reactions (6.1)].

Although clinical studies have shown that rosuvastatin calcium tablets alone does not reduce basal

plasma cortisol concentration or impair adrenal reserve, caution should be exercised if rosuvastatin

calcium tablets are administered concomitantly with drugs that may decrease the levels or activity of

endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.

5.6 Risk of Allergic Reactions due to Tartrazine

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions

(including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C

Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients

who also have aspirin hypersensitivity.

The following serious adverse reactions are discussed in greater detail in other sections of the label:

Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see

Warnings and Precautions (5.1)]

Liver enzyme abnormalities [see Warnings and Precautions (5.2)]

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates

observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of

another drug and may not reflect the rates observed in clinical practice.

In the rosuvastatin calcium tablets controlled clinical trials database (placebo or active-controlled) of

5394 patients with a mean treatment duration of 15 weeks, 1.4% of patients discontinued due to adverse

reactions. The most common adverse reactions that led to treatment discontinuation were:

myalgia

abdominal pain

nausea

The most commonly reported adverse reactions (incidence ≥2%) in the rosuvastatin calcium tablets

controlled clinical trial database of 5394 patients were:

headache

myalgia

abdominal pain

asthenia

nausea

Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate

greater than placebo are shown in Table 1. These studies had a treatment duration of up to 12 weeks.

Table 1. Adverse Reactions1 Reported in ≥2% of Patients Treated with Rosuvastatin Calcium Tablets

and > Placebo in Placebo-Controlled Trials (% of Patients)

Adverse Reactions

Rosuvastatin Calcium Tablets

5 mg

N=291

Rosuvastatin Calcium Tablets

10 mg

N=283

Rosuvastatin Calcium Tablets

20 mg

N=64

Rosuvastatin Calcium Tablets

40 mg

N=106

Total Rosuvastatin Calcium Tablets

5 mg-

40 mg

N=744

Placebo

N=382

Headache

Nausea

Myalgia

Asthenia

Constipation

1 Adverse reactions by COSTART preferred term.

Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity

(including rash, pruritus, urticaria, and angioedema) and pancreatitis. The following laboratory

abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [see

Warnings and Precautions (5.4)]; elevated creatine phosphokinase, transaminases, glucose, glutamyl

transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.

In a clinical trial, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281)

with a mean treatment duration of 1.7 years, 5.6% of subjects treated with rosuvastatin calcium tablets

versus 2.8% of placebo-treated subjects discontinued due to adverse reactions. The most common

adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased,

headache, and nausea.

Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.

Table 2. Adverse Reactions1 Reported in ≥2% of Patients Treated with Rosuvastatin Calcium Tablets

and > Placebo in a Trial (% of Patients)

Adverse Reactions

Rosuvastatin Calcium Tablets

40 mg

N=700

Placebo

N=281

Myalgia

12.7

12.1

Arthralgia

10.1

Headache

Dizziness

Increased CPK

Abdominal pain

ALT >3x ULN2

1 Adverse reactions by MedDRA preferred term.

2 Frequency recorded as abnormal laboratory value.

In a clinical trial, 17,802 participants were treated with rosuvastatin 20 mg (n=8901) or placebo

(n=8901) for a mean duration of 2 years. A higher percentage of rosuvastatin-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. There was a significantly higher frequency of diabetes mellitus reported in

patients taking rosuvastatin (2.8%) versus 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 a HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated

versus placebo-treated patients [see Warnings and Precautions (5.5)].

Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 3.

Table 3. Adverse Reactions1 Reported in ≥2% of Patients Treated with Rosuvastatin Calcium Tablets

and > Placebo in a Trial (% of Patients)

Adverse Reactions

Rosuvastatin Calcium Tablets

20 mg

N=8901

Placebo

N=8901

Myalgia

Arthralgia

Constipation

Diabetes mellitus

Nausea

1 Treatment-emergent adverse reactions by MedDRA preferred term.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of rosuvastatin calcium

tablets: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression,

sleep disorders (including insomnia and nightmares), peripheral neuropathy, interstitial lung disease and

gynecomastia. Because these reactions are reported voluntarily from a population of uncertain size, it is

not always possible to reliably estimate their frequency or establish a causal relationship to drug

exposure.

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see

Warnings and Precautions (5.1)].

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness,

amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been

reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation,

with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

7.1 Cyclosporine

Cyclosporine increased rosuvastatin exposure (AUC) 7fold. Therefore, in patients taking cyclosporine,

the dose of rosuvastatin calcium tablets should not exceed 5 mg once daily [see Dosage and

Administration (2.4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

7.2 Gemfibrozil

Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of

myopathy/rhabdomyolysis, combination therapy with rosuvastatin calcium tablets and gemfibrozil should

be avoided. If used together, the dose of rosuvastatin calcium tablets should not exceed 10 mg once

daily [see Clinical Pharmacology (12.3)].

7.3 Protease Inhibitors

Coadministration of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin

exposure. Simeprevir, which is a hepatitis C virus (HCV) protease inhibitor, or combinations of

atazanavir/ritonavir or lopinavir/ritonavir, which are HIV-1 protease inhibitors, increase rosuvastatin

exposure (AUC) up to threefold [see Table 4 – Clinical Pharmacology (12.3)]. For these protease

inhibitors, the dose of rosuvastatin calcium tablets should not exceed 10 mg once daily. The

combinations of fosamprenavir/ritonavir or tipranavir/ritonavir, which are HIV-1 protease inhibitors,

produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is

coadministered with protease inhibitors [see Dosage and Administration (2.4), Warnings and

Precautions (5.1) and Clinical Pharmacology (12.3)].

7.4 Coumarin Anticoagulants

Rosuvastatin calcium tablets significantly increased INR in patients receiving coumarin anticoagulants.

Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with

rosuvastatin calcium tablets. In patients taking coumarin anticoagulants and rosuvastatin calcium tablets

concomitantly, INR should be determined before starting rosuvastatin calcium tablets and frequently

enough during early therapy to ensure that no significant alteration of INR occurs [see Warnings and

Precautions (5.3)and Clinical Pharmacology (12.3)].

7.5 Niacin

The risk of skeletal muscle effects may be enhanced when rosuvastatin calcium tablets are used in

combination with lipid-modifying doses (≥1 g/day) of niacin; caution should be used when prescribing

with rosuvastatin calcium tablets [see Warnings and Precautions (5.1) ].

7.6 Fenofibrate

When rosuvastatin calcium tablets were coadministered with fenofibrate, no clinically significant

increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of

myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of

fenofibrates, caution should be used when prescribing fenofibrates with rosuvastatin calcium tablets

[see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

7.7 Colchicine

Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase

inhibitors, including rosuvastatin, coadministered with colchicine, and caution should be exercised

when prescribing rosuvastatin calcium tablets with colchicine [see Warnings and Precautions (5.1)].

8.1 Pregnancy

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).

8.2 Lactation

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.

8.3 Females and Males of Reproductive Potential

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.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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) andClinical Pharmacology (12.3)].

8.6 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 and dose adjustment is

required [see Dosage and Administration(2.5),Warnings and Precautions(5.1) and Clinical Pharmacology

(12.3)].

8.7 Hepatic Impairment

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)].

8.8 Asian Patients

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)].

There is no specific treatment in the event of overdose. In the event of overdose, the patient should be

treated symptomatically and supportive measures instituted as required. Hemodialysis does not

significantly enhance clearance of rosuvastatin.

Rosuvastatin calcium is a synthetic lipid-lowering agent for oral administration.

The chemical name for rosuvastatin calcium is (3R, 5S, 6E) -7-[4-(4-Fluorophenyl)-6-(1-methylethyl)-

2-[methyl (methylsulfonyl) amino]-5-pyrimidinyl]-3,5-dihydroxy-6-heptenoic acid calcium salt with the

following structural formula:

[structure]

The molecular formula for rosuvastatin calcium is (C22H27FN3O6S)2Ca and the molecular weight is

1001.14. Rosuvastatin calcium is a white to almost white powder that is sparingly soluble in methanol.

Rosuvastatin calcium is a hydrophilic compound with a partition coefficient of 1.14 by HPLC.

Rosuvastatin calcium tablets for oral administration contain 5, 10, 20, or 40 mg of rosuvastatin and the

following inactive ingredients: Each tablet contains: crospovidone, FD&C blue #2/indigo carmine

aluminum lake, FD&C red #40/allura red AC aluminum lake, hydroxypropyl cellulose, hypromellose,

lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium bicarbonate, talc, titanium

dioxide and triacetin. Additionally 5 mg tablets contain FD&C yellow #5/tartrazine aluminum lake and 10

mg, 20 mg and 40 mg tablets contain FD&C yellow #6/sunset yellow FCF aluminum lake.

12.1 Mechanism of Action

Rosuvastatin calcium tablets are a selective and competitive inhibitor of HMG-CoA reductase, the rate-

limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of

cholesterol. In vivo studies in animals, and in vitro studies in cultured animal and human cells have

shown rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for

cholesterol lowering. In in vivo and in vitro studies, rosuvastatin produces its lipid-modifying effects in

two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake

and catabolism of LDL. Second, rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the

total number of VLDL and LDL particles.

12.3 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 AUC increased in approximate proportion to rosuvastatin

calcium tablets dose. The absolute bioavailability of rosuvastatin is approximately 20%.

Administration of rosuvastatin calcium tablets with food did not affect the AUC of rosuvastatin.

The AUC of rosuvastatin does not differ following evening or morning drug administration.

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.

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.

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.

Specific Populations

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 US, have demonstrated an approximate 2-fold elevation in median

exposure (AUC and Cmax) in Asian subjects when compared with a Caucasian control group.

Gender

There were no differences in plasma concentrations of rosuvastatin between men and women.

Pediatric use information for patients ages 8 to less than 10 years 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.

Geriatric

There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly

populations (age ≥65 years).

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).

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.

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 AUC were increased by 60% and 5%, respectively, as

compared with patients with normal liver function. In patients with Child-Pugh B disease, Cmax and

AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.

Drug-Drug Interactions

Rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically

significant extent.

Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter

organic anion-transporting polyprotein 1B1 (OATP1B1) and efflux transporter breast cancer resistance

protein (BCRP). Concomitant administration of rosuvastatin calcium tablets with medications that are

inhibitors of these transporter proteins (e.g. cyclosporine, certain HIV protease inhibitors) may result in

increased rosuvastatin plasma concentrations and an increased risk of myopathy [see Dosage and

Administration (2.4)]. It is recommended that prescribers consult the relevant product information when

considering administration of such products together with rosuvastatin calcium tablets.

Table 4. Effect of Coadministered Drugs on Rosuvastatin Systemic Exposure

Coadm i n i st e r ed drug and dos i ng reg imen

R os uvas t a t in

Mean Ratio (ratio with/without) coadministered drug)

No Effect=1

Dose (m g)1

Change in AUC

Change inCmax

C y closporine – stab le d o se required

(75 mg – 200 mg B ID)

10 mg QD for

10 d a ys

7.1 2

11 2

At a z an avi r/ riton avir co mbin ation

300 m g /100 mg QD for 8 d a ys

10 mg

3.12

Simeprevir 150 mg QD, 7 days

10 mg , single dose

2.82

(2.3-3.4)3

3.22

(2.6-3.9)3

L opinavir/ritonav ir com b ination

400 m g/100 mg B ID for 17 d a ys

20 mg QD for

7 d a ys

2.12

(1.7-2.6)3

(3.4-6.4)3

Gemfibro z il 600 mg B ID for 7 d a ys

80 mg

1.9 2

(1.6-2.2) 3

2.22

(1.8-2.7) 3

Eltrombopag 75 mg QD, 5 d a ys

10 mg

(1.4-1.7)3

(1.8-2.3) 3

Darunavir 600 m g /riton a vir 100 mg B ID, 7 d a ys

10 mg QD for

7 d a ys

(1-2.1) 3

(1.6-3.6) 3

Tip ran avi r/ riton avir combin ation

500 m g/200 mg B ID for 11 d a ys

10 mg

(1.2-1.6) 3

(1.8-2.7) 3

Droned a rone 400 mg BID

10 mg

It r aco n a z ole 200 mg QD, 5 d a ys

10 mg or 80 mg

(1.2-1.6) 3

(1.1-1.4) 3

(1.2-1.5) 3

(0.9-1.4)3

Ez etimibe 10 mg QD, 14 da ys

10 mg QD for

14 d a ys

(0.9-1.6)3

(0.8-1.6)3

Fo sampre n avir/ritonavir

700 m g/100 mg B ID for 7 d a ys

10 mg

F enofib r ate 67 mg T ID f or 7 d a ys

10 mg

(1.1-1.3)3

Coadm i n i st e r ed drug and dos i ng reg imen

R os uvas t a t in

Rifampicin 450 mg QD, 7 d a ys

20 mg

Aluminum & m a g n esium h yd ro xide combin ati on ant acid

Administ ered simult an eous ly

Administered 2 hours a p art

40 mg

40 mg

0.52

(0.4-0.5)3

(0.7-0.9)3

0.52

(0.4-0.6)3

(0.7-1)3

Ketocona z ole 200 mg B ID for 7 d a ys

80 mg

(0.8-1.2)3

(0.7-1.3)3

Fl ucona zo le 200 mg QD for 11 days

80 mg

(1-1.3)3

(0.9-1.4)3

E r yt hro m y cin 500 mg Q ID for

7 d a ys

80 mg

(0.7-0.9)3

(0.5-0.9)3

1 Single dose unless otherwise noted.

2 Clinically significant [see Dosage and Administration (2) and Warnings and Precautions (5)]

3 Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7 = 30% decrease,

11=11 fold increase in exposure)

Table 5. Effect of Rosuvastatin Coadministration on Systemic Exposure to Other Drugs

Rosuvas t a t in Dos a ge Re g i men

Coadmi n i ste red Drug

Mean Ratio

(ratio with/without

coadministered drug)

No Effect = 1

Name and D ose

Change in AUC

Change in C max

40 mg QD for 10 d a ys

W arfarin1

25 mg si n gle dose

R - W arfarin

(1-1.1)2

S - W arfarin

(1-1.1)2

R - W arfarin

(0.9-1)2

S - W arfarin

(0.9-1.1)2

40 mg QD for 12 d a ys

Di go xin

0.5 mg sin gle dose

(0.9-1.2)2

(0.9-1.2)2

40 mg QD for 28 d a ys

Oral Contra c eptive

(ethi n yl est radiol

0.035 mg & n o r g estrel 0.180, 0.215 and 0.250 mg) QD for 21 Days

EE 1.3

(1.2-1.3)2

NG 1.3

(1.3-1.4)2

EE 1.3

(1.2-1.3)2

NG 1.2

(1.1-1.3)2

EE = ethinyl estradiol, NG = norgestrel

1 Clinically significant pharmacodynamic effects [see Warnings and Precautions (5.3)]

2 Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7=30% decrease,

11=11-fold increase in exposure)

12.5 Pharmacogenomics

Disposition of HMG-CoA reductase inhibitors, including rosuvastatin, involves OATP1B1 and other

transporter proteins. Higher plasma concentrations of rosuvastatin have been reported in very small

groups of patients (n=3 to 5) who have two reduced function alleles of the gene that encodes OATP1B1

(SLCO1B1 521T > C). The frequency of this genotype (i.e., SLCO1B1 521 C/C) is generally lower than

5% in most racial/ethnic groups. The impact of this polymorphism on efficacy and/or safety of

rosuvastatin has not been clearly established.

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

In a 104-week carcinogenicity study in rats at dose levels of 2, 20, 60, or 80 mg/kg/day by oral gavage,

the incidence of uterine stromal polyps was significantly increased in females at 80 mg/kg/day at

systemic exposure 20 times the human exposure at 40 mg/day based on AUC. Increased incidence of

polyps was not seen at lower doses.

In a 107-week carcinogenicity study in mice given 10, 60, or 200 mg/kg/day by oral gavage, an

increased incidence of hepatocellular adenoma/carcinoma was observed at 200 mg/kg/day at systemic

exposures 20 times the human exposure at 40 mg/day based on AUC. An increased incidence of

hepatocellular tumors was not seen at lower doses.

Rosuvastatin was not mutagenic or clastogenic with or without metabolic activation in the Ames test

with Salmonella typhimurium and Escherichia coli, the mouse lymphoma assay, and the chromosomal

aberration assay in Chinese hamster lung cells. Rosuvastatin was negative in the in vivo mouse

micronucleus test.

In rat fertility studies with oral gavage doses of 5, 15, 50 mg/kg/day, males were treated for 9 weeks

prior to and throughout mating and females were treated 2 weeks prior to mating and throughout mating

until gestation day 7. No adverse effect on fertility was observed at 50 mg/kg/day (systemic exposures

up to 10 times the human exposure at 40 mg/day based on AUC). In testicles of dogs treated with

rosuvastatin at 30 mg/kg/day for one month, spermatidic giant cells were seen. Spermatidic giant cells

were observed in monkeys after 6-month treatment at 30 mg/kg/day in addition to vacuolation of

seminiferous tubular epithelium. Exposures in the dog were 20 times and in the monkey 10 times the

human exposure at 40 mg/day based on body surface area. Similar findings have been seen with other

drugs in this class.

13.2 Animal Pharmacology & OR Toxicology

Central Nervous System Toxicity

CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell

infiltration of perivascular spaces, have been observed in dogs treated with several other members of

this drug class. A chemically similar drug in this class produced dose-dependent optic nerve

degeneration (Wallerian degeneration of retinogeniculate fibers) in dogs, at a dose that produced

plasma drug levels about 30 times higher than the mean drug level in humans taking the highest

recommended dose. Edema, hemorrhage, and partial necrosis in the interstitium of the choroid plexus

was observed in a female dog sacrificed moribund at day 24 at 90 mg/kg/day by oral gavage (systemic

exposures 100 times the human exposure at 40 mg/day based on AUC). Corneal opacity was seen in

dogs treated for 52 weeks at 6 mg/kg/day by oral gavage (systemic exposures 20 times the human

exposure at 40 mg/day based on AUC). Cataracts were seen in dogs treated for 12 weeks by oral

gavage at 30 mg/kg/day (systemic exposures 60 times the human exposure at 40 mg/day based on AUC).

Retinal dysplasia and retinal loss were seen in dogs treated for 4 weeks by oral gavage at 90 mg/kg/day

(systemic exposures 100 times the human exposure at 40 mg/day based on AUC). Doses ≤30 mg/kg/day

(systemic exposures ≤60 times the human exposure at 40 mg/day based on AUC) did not reveal retinal

findings during treatment for up to one year.

Juvenile Toxicology Study

In a juvenile study, rats were dosed by oral gavage with 10 or 50 mg/kg/day from weaning for 9 weeks

prior to pairing, throughout pairing and up to the day before necropsy for males or up to gestation day 7

for females. No effects on sexual development, testicular and epididymal appearance or fertility were

observed at either dose level.

Pediatric information 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.

14.3 Hypertriglyceridemia

Dose-Response Study: In a double-blind, placebo-controlled dose-response study in patients with

baseline TG levels from 273 to 817 mg/dL, rosuvastatin calcium tablets given as a single daily dose (5

to 40 mg) over 6 weeks significantly reduced serum TG levels (Table 9).

Table 9. Dose-Response in Patients with Primary Hypertriglyceridemia over 6 Weeks Dosing Median

(Min, Max) Percent Change from Baseline

Dose

Placebo

(n=26)

Rosuvastatin Calcium Tablets

5 mg

(n=25)

Rosuvastatin Calcium Tablets

10 mg

(n=23)

Rosuvastatin Calcium Tablets

20 mg

(n=27)

Rosuvastatin Calcium Tablets

40 mg

(n=25)

T ri gl ycer ides

1 ( -40, 72)

-21 ( -58, 38)

-37 ( -65, 5)

-37 ( -72, 11)

-43 ( -80, - 7)

nonHD L -C

2 ( - 13, 19)

-29 ( -43, - 8)

-49 ( -59, -20)

-43 ( -74, 12)

-51 ( -62, - 6)

V LDL -C

2 ( -36, 53)

-25 ( -62, 49)

-48 ( -72, 14)

-49 ( -83, 20)

-56 ( -83, 10)

T ot al -C

1 ( -13, 17)

-24 ( -40, - 4)

-40 ( -51, -14)

-34 ( -61 , -11)

-40 ( -51, - 4)

LD L -C

5 ( - 30, 52)

-28 ( -71, 2)

-45 ( -59, 7)

-31 ( -66, 34)

-43 ( -61, - 3)

HD L -C

-3 ( - 25, 18)

3 ( -38, 33)

8 ( -8, 24)

22 ( -5, 50)

17 ( -14, 63)

14.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)

In a randomized, multicenter, double-blind crossover study, 32 patients (27 with є2/є2 and 4 with apo E

mutation [Arg145Cys] with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia) entered a

6-week dietary lead-in period on the NCEP Therapeutic Lifestyle Change (TLC) diet. Following

dietary lead-in, patients were randomized to a sequence of treatments in conjunction with the TLC diet

for 6 weeks each: rosuvastatin 10 mg followed by rosuvastatin 20 mg or rosuvastatin 20 mg followed

by rosuvastatin 10 mg. Rosuvastatin calcium tablets reduced non HDL-C (primary end point) and

circulating remnant lipoprotein levels. Results are shown in the table below.

Table 10. Lipid-modifying Effects of Rosuvastatin 10 mg and 20 mg in Primary Dysbetalipoproteinemia

(Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline

(N=32)

Median at Baseline (mg/dL)

Median percent change from baseline

(95 % CI) Rosuvastatin Calcium Tablets 10 mg

Median percent change from baseline (95% CI) Rosuvastatin Calcium Tablets 20 mg

Total-C

342.5

-43.3

(-46.9,-37.5)

-47.6

(-51.6,-42.8)

Triglycerides

503.5

-40.1

(-44.9, -33.6)

(-52.5, -33.1)

NonHDL-C

294.5

-48.2

(-56.7, -45.6)

-56.4

(-61.4, -48.5)

VLDL-C + IDL- C

209.5

-46.8

(-53.7, -39.4)

-56.2

(-67.7, -43.7)

LDL-C

112.5

-54.4

(-59.1, -47.3)

-57.3

(-59.4, -52.1)

HDL-C

35.5

10.2

(1.9, 12.3)

11.2

(8.3, 20.5)

RLP-C

-56.4

(-67.1, -49)

-64.9

(-74, -56.6)

Apo-E

-42.9

(-46.3, -33.3)

-42.5

(-47.1, -35.6)

14.5 Homozygous Familial Hypercholesterolemia

Dose-Titration Study: In an open-label, forced-titration study, homozygous FH patients (n=40, 8 to 63

years) were evaluated for their response to rosuvastatin calcium tablets 20 to 40 mg titrated at a 6-week

interval. In the overall population, the mean LDL-C reduction from baseline was 22%. About one-third

of the patients benefited from increasing their dose from 20 mg to 40 mg with further LDL lowering of

greater than 6%. In the 27 patients with at least a 15% reduction in LDL-C, the mean LDL-C reduction

was 30% (median 28% reduction). Among 13 patients with an LDL-C reduction of <15%, 3 had no

change or an increase in LDL-C. Reductions in LDL-C of 15% or greater were observed in 3 of 5

patients with known receptor negative status.

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 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. They are supplied as follows.

Bottle of 90 Tablets

Blister pack of 100 (10×10) Unit dose tablets

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.

Bottle of 90 Tablets

Blister pack of 100 (10×10) Unit dose tablets

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.

Bottle of 90 Tablets

Blister pack of 100 (10×10) Unit dose tablets

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.

Bottle of 30 Tablets

Blister pack of 100 (10×10) Unit dose tablets

Storage

Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from moisture.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Patients should be instructed not to take 2 doses of rosuvastatin calcium tablets within 12 hours of each

other.

Skeletal Muscle Effects

Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness,

particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after

discontinuing rosuvastatin calcium tablets.

Concomitant Use of Antacids

When taking rosuvastatin calcium tablets with an aluminum and magnesium hydroxide combination

antacid, the antacid should be taken at least 2 hours after rosuvastatin calcium tablets administration.

Embryofetal Toxicity

Advise females of reproductive potential of the risk to a fetus, to use effective contraception during

treatment, and to inform their healthcare provider of a known or suspected pregnancy. [see

Contraindications (4)and Use in Specific Populations (8.1, 8.3)].

Lactation

Advise women not to breastfeed during treatment with rosuvastatin calcium tablets [see

Contraindications (4)and Use in Specific Populations (8.2)].

Liver Enzymes

It is recommended that liver enzyme tests be performed before the initiation of rosuvastatin calcium

tablets and if signs or symptoms of liver injury occur. All patients treated with rosuvastatin calcium

tablets should be advised to promptly report any symptoms that may indicate liver injury, including

fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

Manufactured for:

Camber Pharmaceuticals, Inc.

Piscataway, NJ 08854

Manufactured by:

[hetero]

HETEROTM

HETERO LABS LIMITED 2038142

Unit V, Polepally, Jadcherla,

Mahaboob Nagar-509 301, India.

Barcode

Revised: July 2016

Rosuvastatin Calcium

(roe-soo-va-STAT-in KAL-see-um)

Tablets

Read this Patient Information carefully before you start taking rosuvastatin calcium tablets and each time

you get a refill. If you have any questions about rosuvastatin calcium tablets, ask your doctor. Only your

doctor can determine if rosuvastatin calcium tablets are right for you.

What is rosuvastatin calcium tablet?

Rosuvastatin calcium tablet is a prescription medicine that contains a cholesterol-lowering medicine

called rosuvastatin calcium. Most of the cholesterol in your blood is made in the liver. Rosuvastatin

calcium tablets works by reducing cholesterol in two ways: rosuvastatin calcium tablets blocks an

enzyme in the liver causing the liver to make less cholesterol, and rosuvastatin calcium tablets increases

the uptake and breakdown by the liver of cholesterol already in the blood.

Rosuvastatin calcium tablets are used along with diet to:

o lower the level of your “bad” cholesterol (LDL)

o increase the level of your “good” cholesterol (HDL)

o lower the level of fat in your blood (triglycerides)

Rosuvastatin calcium tablets are used to treat:

o adults who cannot control their cholesterol levels by diet and exercise alone

It is not known if rosuvastatin calcium tablets are safe and effective in people who have Fredrickson

Type I and V dyslipidemias.

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.

Who should not take rosuvastatin calcium tablets?

Do not take rosuvastatin calcium tablets if you:

are allergic to rosuvastatin calcium or any of the ingredients in rosuvastatin calcium tablets. See the

end of this leaflet for a complete list of ingredients in rosuvastatin calcium tablets.

have liver problems.

are pregnant or think you may be pregnant, or are planning to become pregnant. Rosuvastatin calcium

tablets may harm your unborn baby. If you become pregnant, stop taking rosuvastatin calcium tablets and

call your doctor right away. If you are not planning to become pregnant you should use effective birth

control (contraception) while you are taking rosuvastatin calcium tablets.

are breastfeeding. Medicines like rosuvastatin calcium can pass into your breast milk and may harm

your baby.

What should I tell my doctor before and while taking rosuvastatin calcium tablets?

Tell your doctor if you:

have unexplained muscle aches or weakness

have or have had kidney problems

have or have had liver problems

drink more than 2 glasses of alcohol daily

have thyroid problems

are 65 years of age or older

are of Asian descent

are pregnant or think you may be pregnant, or are planning to become pregnant

are breastfeeding

Tell your doctor about all the medicines you take, including prescription and over-the-counter

medicines, vitamins, and herbal supplements.

Talk to your doctor before you start taking any new medicines.

Taking rosuvastatin calcium tablets with certain other medicines may affect each other causing side

effects. Rosuvastatin calcium tablets may affect the way other medicines work, and other medicines may

affect how rosuvastatin calcium tablets works.

Especially tell your doctor if you take:

cyclosporine (a medicine for your immune system)

gemfibrozil (a fibric acid medicine for lowering cholesterol)

anti-viral medicines including HIV or hepatitis C protease inhibitors (such as lopinavir, ritonavir,

fosamprenavir, tipranavir, atazanavir, or simeprevir)

certain anti-fungal medicines (such as itraconazole, ketoconazole and fluconazole)

coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)

niacin or nicotinic acid

fibric acid derivatives (such as fenofibrate)

colchicine (a medicine used to treat gout)

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know all of the medicines you take. Keep a list of them to show your doctor and pharmacist when you

get new medicine.

How should I take rosuvastatin calcium tablets?

Take rosuvastatin calcium tablets exactly as your doctor tells you to take it.

Take rosuvastatin calcium tablets, by mouth, 1 time each day. Swallow the tablet whole.

Rosuvastatin calcium tablets can be taken at any time of day, with or without food.

Do not change your dose or stop rosuvastatin calcium tablets without talking to your doctor, even if

you are feeling well.

Your doctor may do blood tests to check your cholesterol levels before and during your treatment

with rosuvastatin calcium tablets. Your doctor may change your dose of rosuvastatin calcium tablets if

needed.

Your doctor may start you on a cholesterol lowering diet before giving you rosuvastatin calcium

tablets. Stay on this diet when you take rosuvastatin calcium tablets.

Wait at least 2 hours after taking rosuvastatin calcium tablets to take an antacid that contains a

combination of aluminum and magnesium hydroxide.

If you miss a dose of rosuvastatin calcium tablets, take it as soon as you remember. However, do not

take 2 doses of rosuvastatin calcium tablets within 12 hours of each other.

If you take too much rosuvastatin calcium tablets or overdose, call your doctor or go to the nearest

hospital emergency room right away.

What are the Possible Side Effects of rosuvastatin calcium tablets?

Rosuvastatin calcium tablets may cause serious side effects, including:

Muscle pain, tenderness and weakness (myopathy). Muscle problems, including muscle breakdown, can

be serious in some people and rarely cause kidney damage that can lead to death. Tell your doctor right

away if:

o you have unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel

more tired than usual, while you take rosuvastatin calcium tablets.

o you have muscle problems that do not go away even after your doctor has told you to stop taking

rosuvastatin calcium tablets. Your doctor may do further tests to diagnose the cause of your muscle

problems.

Your chances of getting muscle problems are higher if you:

o are taking certain other medicines while you take rosuvastatin calcium tablets

o are 65 years of age or older

o have thyroid problems (hypothyroidism) that are not controlled

o have kidney problems

o are taking higher doses of rosuvastatin calcium tablets.

Liver problems. Your doctor should do blood tests to check your liver before you start taking

rosuvastatin calcium tablets and if you have symptoms of liver problems while you take rosuvastatin

calcium tablets. Call your doctor right away if you have any of the following symptoms of liver

problems:

o feel unusually tired or weak

o loss of appetite

o upper belly pain

o dark urine

o yellowing of your skin or the whites of your eyes

The most common side effects may include: headache, muscle aches and pains, abdominal pain,

weakness, and nausea.

Additional side effects that have been reported with rosuvastatin calcium tablets include memory loss

and confusion.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of rosuvastatin calcium tablets. For more information, ask

your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

How should I store rosuvastatin calcium tablets?

Store rosuvastatin calcium tablet at room temperature, between 68° to 77°F (20° to 25°C) and in a dry

place.

Safely throw away medicine that is out of date or no longer needed.

Keep rosuvastatin calcium tablets and all medicines out of the reach of children.

What are the Ingredients in rosuvastatin calcium tablets?

Active Ingredient: rosuvastatin as rosuvastatin calcium

Inactive Ingredients: crospovidone, FD&C blue #2/indigo carmine aluminum lake, FD&C red #40/allura

red AC aluminum lake, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium

stearate, microcrystalline cellulose, sodium bicarbonate, talc, titanium dioxide and triacetin.

Additionally 5 mg tablets contain FD&C yellow #5/tartrazine aluminum lake and 10 mg, 20 mg and 40 mg

tablets contain FD&C yellow #6/sunset yellow FCF aluminum lake.

General Information about the safe and effective use of rosuvastatin calcium tablets

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

Do not use rosuvastatin calcium tablets for a condition for which it was not prescribed. Do not give

rosuvastatin calcium tablets to other people, even if they have the same medical condition you have. It

may harm them.

You can ask your pharmacist or doctor for information about rosuvastatin calcium tablets that is written

for health professionals.

Manufactured for:

Camber Pharmaceuticals, Inc.

Piscataway, NJ 08854

Manufactured by:

[hetero1]

HETEROTM

HETERO LABS LIMITED

Unit V, Polepally, Jadcherla,

Mahaboob Nagar-509 301, India.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Revised: July 2016

ROSUVASTATIN CALCIUM

rosuvastatin calcium tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 19 19 -70 1(NDC:31722-8 8 4)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

RO SUVASTATIN CALCIUM (UNII: 8 3MVU38 M7Q) (ROSUVASTATIN - UNII:413KH5ZJ73)

ROSUVASTATIN

20 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

TALC (UNII: 7SEV7J4R1U)

TRIACETIN (UNII: XHX3C3X6 73)

CRO SPO VIDO NE ( 15 MPA.S AT 5%) (UNII: 6 8 40 19 6 0 MK)

HYDRO XYPRO PYL CELLULO SE ( 16 0 0 0 0 0 WAMW) (UNII: RFW2ET6 71P)

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

SO DIUM BICARBO NATE (UNII: 8 MDF5V39 QO)

Dire ct_Rx

Product Characteristics

Color

pink ((Light pink to pink))

S core

no sco re

S hap e

ROUND

S iz e

8 mm

Flavor

Imprint Code

H;R5

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 19 19 -70 1-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /19 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 76 16

0 8 /19 /20 19

Labeler -

Direct_Rx (079254320)

Registrant -

Direct_Rx (079254320)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Dire c t_Rx

0 79 254320

re pa c k(6 19 19 -70 1)

Revised: 8/2019

Similar products

Search alerts related to this product

View documents history

Share this information