NDC 47335-985 Ezallor Sprinkle

Rosuvastatin

NDC Product Code 47335-985

NDC Code: 47335-985

Proprietary Name: Ezallor Sprinkle What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Rosuvastatin What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.


Product Characteristics
Color(s):
PINK (C48328 - PINK CAP)
WHITE (C48325 - OFF WHITE BODY)
PURPLE (C48327 - PURPLE CAP)
Shape: CAPSULE (C48336)
Size(s):
16 MM
Imprint(s):
984;984
985;985
Score: 1

Code Structure
  • 47335 - Sun Pharmaceutical Industries, Inc.
    • 47335-985 - Ezallor Sprinkle

NDC 47335-985-64

Package Description: 3 BLISTER PACK in 1 CARTON > 10 CAPSULE in 1 BLISTER PACK (47335-985-60)

NDC 47335-985-81

Package Description: 90 CAPSULE in 1 BOTTLE

NDC 47335-985-83

Package Description: 30 CAPSULE in 1 BOTTLE

NDC Product Information

Ezallor Sprinkle with NDC 47335-985 is a a human prescription drug product labeled by Sun Pharmaceutical Industries, Inc.. The generic name of Ezallor Sprinkle is rosuvastatin. The product's dosage form is capsule and is administered via oral form.

Labeler Name: Sun Pharmaceutical Industries, Inc.

Dosage Form: Capsule - A solid oral dosage form consisting of a shell and a filling. The shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band. Capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.


Ezallor Sprinkle Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • ROSUVASTATIN CALCIUM 10 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • CROSPOVIDONE, UNSPECIFIED (UNII: 2S7830E561)
  • MANNITOL (UNII: 3OWL53L36A)
  • MAGNESIUM OXIDE (UNII: 3A3U0GI71G)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • SODIUM CITRATE, UNSPECIFIED FORM (UNII: 1Q73Q2JULR)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • D&C RED NO. 28 (UNII: 767IP0Y5NH)
  • SHELLAC (UNII: 46N107B71O)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • POTASSIUM HYDROXIDE (UNII: WZH3C48M4T)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • CROSPOVIDONE, UNSPECIFIED (UNII: 2S7830E561)
  • MANNITOL (UNII: 3OWL53L36A)
  • MAGNESIUM OXIDE (UNII: 3A3U0GI71G)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • SODIUM CITRATE, UNSPECIFIED FORM (UNII: 1Q73Q2JULR)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • D&C RED NO. 28 (UNII: 767IP0Y5NH)
  • SHELLAC (UNII: 46N107B71O)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • POTASSIUM HYDROXIDE (UNII: WZH3C48M4T)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • HMG-CoA Reductase Inhibitor - [EPC] (Established Pharmacologic Class)
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sun Pharmaceutical Industries, Inc.
Labeler Code: 47335
FDA Application Number: NDA208647 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 05-04-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Ezallor Sprinkle Product Label Images

Ezallor Sprinkle Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

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.

1.1 Hypertriglyceridemia

EZALLOR Sprinkle is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.

1.2 Primary Dysbetalipoproteinemia (Type Iii Hyperlipoproteinemia)

EZALLOR Sprinkle is indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).

1.3 Adult Patients With Homozygous Familial Hypercholesterolemia

EZALLOR Sprinkle is 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.

1.4 Limitations Of Use

EZALLOR Sprinkle has not been studied in Fredrickson Type I and V dyslipidemias.

2.1 General Dosing Information

The dose range for EZALLOR Sprinkle in adults is 5 mg to 40 mg orally once daily. The usual starting dose is 10 mg to 20 mg once daily. The usual starting dose in adult patients with homozygous familial hypercholesterolemia is 20 mg once daily. The maximum EZALLOR Sprinkle 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)]. EZALLOR Sprinkle can be administered as a single dose at any time of day, with or without food. Swallow capsules whole. Do not crush or chew. For patients who cannot swallow capsules, the capsules can be opened for administration [see Dosage and Administration (2.5)].When initiating EZALLOR Sprinkle therapy or switching from another HMG-CoA reductase inhibitor therapy, the appropriate EZALLOR Sprinkle 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 EZALLOR Sprinkle, 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.

2.2 Dosing In Asian Patients

In Asian patients, consider initiation of EZALLOR Sprinkle 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 once daily [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3)].

2.3 Use With Concomitant Therapy

Patients taking cyclosporineThe dose of EZALLOR Sprinkle should not exceed 5 mg once daily [see Warnings and Precautions (5.1), Drug Interactions (7.1) and Clinical Pharmacology (12.3)].Patients taking gemfibrozilAvoid concomitant use of EZALLOR Sprinkle with gemfibrozil. If concomitant use cannot be avoided, initiate EZALLOR Sprinkle at 5 mg once daily. The dose of EZALLOR Sprinkle 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 simeprevirInitiate EZALLOR Sprinkle therapy with 5 mg once daily. The dose of EZALLOR Sprinkleshould not exceed 10 mg once daily [see Warnings and Precautions (5.1), Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

2.4 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 EZALLOR Sprinkle 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)].

2.5 Administration Options

See the EZALLOR Sprinkle full Instructions for Use for proper preparation and administration instructions. Oral Administration For patients who have difficulty swallowing capsules, the rosuvastatin capsule can be opened, the granules inside the capsule carefully emptied onto one teaspoon of applesauce. The granules with the applesauce should be swallowed immediately, without chewing. The granules with applesauce must be used immediately after preparation and not be stored for future use. If it is not used in its entirety, the remaining contents should be discarded immediately.Nasogastric Tube (≥16 French) Administration For patients who have a nasogastric tube in place, the rosuvastatin capsule can be opened and the intact granules emptied into a 60 mL catheter tipped syringe and add 40 mL of water. Replace the plunger and shake the syringe vigorously for 15 seconds. The granules in rosuvastatin may start dissolving which is acceptable. Attach the syringe to a nasogastric tube (≥16-French) and deliver the contents of the syringe through the nasogastric tube into the stomach. After administering the granules, the nasogastric tube should be flushed with 20 mL of additional water. The mixture must be used immediately after preparation and not be stored for future use. If it is not used in its entirety, the remaining mixture should be discarded immediately. Use with any other liquids is not recommended.

3 Dosage Forms And Strengths

5 mg: Hard gelatin capsule, Size “3” pink cap/off white body, imprinted axially with “984” on cap and body in black ink filled with yellow colored granules.10 mg: Hard gelatin capsule, Size “3” purple cap/off white body, imprinted axially with “985” on cap and body in black ink filled with yellow colored granules.20 mg: Hard gelatin capsule, Size “1” blue cap/off white body, imprinted axially with “986” on cap and body in black ink filled with yellow colored granules.40 mg: Hard gelatin capsule, Size “0el” green cap/white body, imprinted axially with “987” on cap and body in black ink filled with yellow colored granules.

4 Contraindications

  • EZALLOR Sprinkle is 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 [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 is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require EZALLOR Sprinkle 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. These risks can occur at any dose level, but are increased at the highest dose (40 mg).EZALLOR Sprinkle 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 EZALLOR Sprinklemay 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 EZALLOR Sprinklewith colchicine [see Drug Interactions (7.7)].EZALLOR Sprinkle therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. EZALLOR Sprinkle 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 EZALLOR Sprinkle.

5.2 Liver Enzyme Abnormalities

It is recommended that liver enzyme tests be performed before the initiation of EZALLOR Sprinkle, 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. 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 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 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 EZALLOR Sprinkle, promptly interrupt therapy. If an alternate etiology is not found, do not restart EZALLOR Sprinkle. EZALLOR Sprinkle 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 EZALLOR Sprinkle [see Contraindications (4)].

5.3 Concomitant Coumarin Anticoagulants

Caution should be exercised when anticoagulants are given in conjunction with EZALLOR Sprinkle because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR. In patients taking coumarin anticoagulants and EZALLOR Sprinkle concomitantly, INR should be determined before starting EZALLOR Sprinkle 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 clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among rosuvastatin treated patients. These findings were more frequent in patients taking rosuvastatin 40 mg, when compared to lower doses of rosuvastatin 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 EZALLOR Sprinkle 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. Based on clinical trial data with rosuvastatin, 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 alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if EZALLOR Sprinkle is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.

6 Adverse Reactions

  • 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 controlled clinical trials database (placebo or active-controlled) of 5,394 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:myalgiaabdominal painnauseaThe most commonly reported adverse reactions (incidence ≥ 2%) in the rosuvastatin controlled clinical trial database of 5,394 patients were:headachemyalgiaabdominal painasthenianauseaAdverse 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 and > Placebo in Placebo-Controlled Trials (% of Patients)
  • Adverse ReactionsRosuvastatin5 mgN=291Rosuvastatin10 mgN=283 Rosuvastatin20 mgN=64 Rosuvastatin40 mgN=106 Total Rosuvastatin5 mg to 40 mgN=744 PlaceboN=382   Headache 5.5 4.9 3.1 8.5 5.5 5 Nausea 3.8 3.5 6.3 0 3.4 3.1 Myalgia 3.1 2.1 6.3 1.9 2.8 1.3 Asthenia 2.4 3.2 4.7 0.9 2.7 2.6 Constipation 2.1 2.1 4.7 2.8 2.4 2.41 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 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 and > Placebo in a Trial (% of Patients)
  • Adverse ReactionsRosuvastatin 40 mgN=700PlaceboN=281  Myalgia  12.712.1 Arthralgia  10.17.1 Headache 6.45.3 Dizziness  4.02.8 Increased CPK  2.60.7 Abdominal Pain 2.41.8 ALT >3x ULN2  2.20.7 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=8,901) or placebo (n=8,901) 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 and > Placebo in a Trial (% of Patients)
  • Adverse Reactions Rosuvastatin 20 mgN=8,901PlaceboN=8,901Myalgia 7.6 6.6Arthralgia 3.8 3.2Constipation3.3 3.0Diabetes mellitus 2.8 2.3Nausea 2.4 2.31 Treatment-emergent adverse reactions by MedDRA preferred term.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of rosuvastatin: 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, and 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 and may result in increased risk of myopathy. Therefore, in patients taking cyclosporine, the dose of EZALLOR Sprinkle 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 EZALLOR Sprinkle and gemfibrozil should be avoided. If used together, the dose of EZALLOR Sprinkle 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 and may increase risk of myopathy. 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 [see Table 4 – Clinical Pharmacology (12.3)]. For these protease inhibitors, the dose of EZALLOR Sprinkle 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 EZALLOR Sprinkle 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 significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with EZALLOR Sprinkle. In patients taking coumarin anticoagulants and EZALLOR Sprinkle concomitantly, INR should be determined before starting EZALLOR Sprinkle 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 EZALLOR Sprinkle is used in combination with lipid-modifying doses (≥1 g/day) of niacin; caution should be used when prescribing with EZALLOR Sprinkle[see Warnings and Precautions (5.1)].

7.6 Fenofibrate

When rosuvastatin was 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 EZALLOR Sprinkle [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 EZALLOR Sprinkle with colchicine [see Warnings and Precautions (5.1)].

8.1 Pregnancy

Risk SummaryEZALLOR Sprinkle is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit to therapy with EZALLOR Sprinkle during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, EZALLOR Sprinkle may cause fetal harm when administered to pregnant women. EZALLOR Sprinkle 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.DataHuman 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 SummaryEZALLOR Sprinkle use is contraindicated during breastfeeding [see Contraindications (4)]. Limited data indicate that rosuvastatin 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 EZALLOR Sprinkle.

8.3 Females And Males Of Reproductive Potential

Contraception EZALLOR Sprinkle 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 EZALLOR Sprinkle.

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, 3,159 (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 EZALLOR Sprinkle should be prescribed with caution in the elderly [see Warnings and Precautions (5.1) and Clinical 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

EZALLOR Sprinkle is 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; EZALLOR Sprinkle 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. EZALLOR Sprinkle dosage should be adjusted in Asian patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

10 Overdosage

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.

11 Description

Rosuvastatin calcium is a synthetic lipid-lowering agent for oral administration.The chemical name for rosuvastatin calcium is bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt with the following structural formula:The molecular formula for rosuvastatin calcium is (C22H27FN3O6S)2·Ca and the molecular weight is 1,001.14. Rosuvastatin calcium is off-white to light yellow amorphous powder that is slightly soluble in water and methanol, and insoluble in ethanol. Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 0.13 at pH of 7.Each rosuvastatin capsule for oral administration contains 5 mg, 10 mg, 20 mg, or 40 mg of rosuvastatin (present as 5.198 mg, 10.395 mg, 20.790 mg, or 41.580 mg of rosuvastatin calcium) in the form of granules with the following inactive ingredients: microcrystalline cellulose, crospovidone, mannitol, magnesium oxide, ferric oxide, sodium citrate, hypromellose, polyethylene glycol 4000, and silicon dioxide. The capsule shells have the following inactive ingredients: gelatin, titanium dioxide, water, and sodium lauryl sulfate. Additionally following colorants are used in capsules: FD&C Red 40 (5 mg), FD&C Blue 1 (5 mg, 10 mg, 20 mg), D&C Red 28 (5 mg, 10 mg), FD&C Red 3 (20 mg), and FD&C Green 3 (40 mg). The imprinting black ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, purified water, and potassium hydroxide.

12.1 Mechanism Of Action

Rosuvastatin is 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.

12.2 Pharmacodynamics

Rosuvastatin dose dependently reduces elevated LDL-cholesterol and reduces total cholesterol and triglycerides and increases HDL-cholesterol [see Clinical Studies (14)]. A therapeutic response to rosuvastatin is evident within 1 week of commencing therapy and 90% of maximum response is usually achieved in 2 weeks. The maximum response is usually achieved by 4 weeks and is maintained after that. Individualization of drug dosage should be based on the therapeutic response [see Dosage and Administration (2)].

12.3 Pharmacokinetics

AbsorptionIn 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 dose. The absolute bioavailability of rosuvastatin is approximately 20%.Administration of rosuvastatin with food did not affect the AUC of rosuvastatin.The AUC of rosuvastatin does not differ following evening or morning drug administration.DistributionMean 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.EliminationRosuvastatin is primarily eliminated by excretion in the feces. The elimination half-life of rosuvastatin is approximately 19 hours.MetabolismRosuvastatin 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. ExcretionFollowing oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%).After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.Specific PopulationsRacial or Ethnic Groups 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. Male and Female PatientsThere were no differences in plasma concentrations of rosuvastatin between men and women.Geriatric PatientsThere were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥ 65 years).Patients with Renal ImpairmentMild 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).HemodialysisSteady-state plasma concentrations of rosuvastatin in patients on chronic hemodialysis were approximately 50% greater compared with healthy volunteer subjects with normal renal function. Patients with Hepatic ImpairmentIn 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 Interaction StudiesRosuvastatin 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 organic anion-transporting polyproteins (OATP1B1, OATP1B3) and efflux transporter breast cancer resistance protein (BCRP). Concomitant administration of rosuvastatin with medications that are inhibitors of these transporter proteins (e.g., cyclosporine, certain HIV protease inhibitors) may result in increased rosuvastatin plasma concentrations [see Dosage and Administration (2.3) and Drug Interactions (7.1, 7.3)]. Table 4. Effect of Coadministered Drugs on Rosuvastatin Systemic ExposureCoadministered drug and dosing regimenRosuvastatin  Mean Ratio (ratio with/without coadministered drug) No Effect = 1 Dose (mg)1Change in AUCChange in CmaxCyclosporine - stable dose required(75 mg to 200 mg BID)10 mg QD for 10 days 7.12112Atazanavir/ritonavir combination 300 mg/100 mg QD for 8 days10 mg3.1272Simeprevir 150 mg QD, 7 days10 mg, single dose2.82(2.3 to 3.4)33.22(2.6 to 3.9)3Lopinavir/ritonavir combination 400 mg/100 mg BID for 17 days20 mg QD for 7 days2.12(1.7 to 2.6)352(3.4 to 6.4)3Gemfibrozil 600 mg BID for 7 days80 mg1.92(1.6 to 2.2)32.22(1.8 to 2.7)3Eltrombopag 75 mg QD, 5 days10 mg1.6 (1.4 to 1.7)32 (1.8 to 2.3)3Darunavir 600 mg/ritonavir 100 mg BID, 7 days10 mg QD for 7 days1.5 (1 to 2.1)32.4 (1.6 to 3.6)3Tipranavir/ritonavir combination 500 mg/200mg BID for 11 days10 mg1.4 (1.2 to 1.6)32.2 (1.8 to 2.7)3Dronedarone 400 mg BID10 mg1.4 Itraconazole 200 mg QD, 5 days10 mg or 80 mg1.4 (1.2 to 1.6)31.3 (1.1 to 1.4)31.4 (1.2 to 1.5)31.2 (0.9 to 1.4)3Ezetimibe 10 mg QD, 14 days10 mg QD for 14 days1.2 (0.9 to 1.6)31.2(0.8 to 1.6)3Fosamprenavir/ritonavir 700 mg/100 mg BID for 7 days10 mg1.11.5Fenofibrate 67 mg TID for 7 days10 mg↔1.2 (1.1 to 1.3)3Rifampicin 450 mg QD, 7 days20 mg↔ Aluminum & magnesium hydroxide combination antacidAdministered simultaneously Administered 2 hours apart  40 mg 40 mg  0.52(0.4 to 0.5)30.8(0.7 to 0.9)3  0.52(0.4 to 0.6)30.8 (0.7 to 1)3Ketoconazole 200 BID for 7 days80 mg1(0.8 to 1.2)31(0.7 to 1.3)3Fluconazole 200 mg QD for 11 days80 mg1.1 (1 to 1.3)31.1(0.9 to 1.4)3Erythromycin 500 mg QID for 7 days80 mg0.8 (0.7 to 0.9)30.7 (0.5 to 0.9)31   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)QD: Once dailyBID: 2 times a dayTID: 3 times a dayQID: 4 times a day Table 5. Effect of Rosuvastatin Coadministration on Systemic Exposure to Other DrugsRosuvastatin Dosage RegimenCoadministered DrugMean Ratio (ratio with/without coadministered drug) No Effect = 1 Name and DoseChange in AUCChange in Cmax40 mg QD for 10 daysWarfarin125 mg single doseR-Warfarin 1(1 to 1.1)2S-Warfarin 1.1 (1 to 1.1)2R-Warfarin 1(0.9 to 1)2S-Warfarin 1 (0.9 to 1.1)240 mg QD for 12 days Digoxin 0.5 mg single dose1 (0.9 to 1.2)21(0.9 to 1.2)240 mg QD for 28 days Oral Contraceptive(ethinyl estradiol 0.035 mg & norgestrel 0.180, 0.215 and 0.250 mg) QD for 21 DaysEE 1.3(1.2 to 1.3)2NG 1.3(1.3 to 1.4)2EE 1.3 (1.2 to 1.3)2NG 1.2 (1.1 to 1.3)2EE = ethinyl estradiol, NG = norgestrel1   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) QD: Once daily

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 Toxicology And/Or Pharmacology

Central Nervous System ToxicityCNS 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.

14.1 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 given as a single daily dose (5 mg 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)  Rosuvastatin5 mg(n=25)  Rosuvastatin10 mg(n=23)  Rosuvastatin20 mg(n=27)  Rosuvastatin40 mg(n=25)  Triglycerides   1 (-40, 72)  -21 (-58, 38)  -37 (-65, 5)  -37 (-72, 11)  -43 (-80, -7)  nonHDL-C   2 (-13, 19)  -29 (-43, -8)  -49 (-59, -20)  -43 (-74, 12)  -51 (-62, -6)  VLDL-C   2 (-36, 53)  -25 (-62, 49)  -48 (-72, 14)  -49 (-83, 20)  -56 (-83, 10)  Total-C   1 (-13, 17)  -24 (-40, -4)  -40 (-51, -14)  -34 (-61, -11)  -40 (-51, -4)  LDL-C   5 (-30, 52)  -28 (-71, 2)  -45 (-59, 7)  -31 (-66, 34)  -43 (-61, -3)  HDL-C   -3 (-25, 18)  3 (-38, 33)  8 (-8, 24)  22 (-5, 50)  17 (-14, 63)

14.2 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 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 10 mgMedian percent change from baseline(95% CI)Rosuvastatin 20 mgTotal-C 342.5-43.3 (-46.9, -37.5)-47.6 (-51.6,-42.8)Triglycerides 503.5-40.1 (-44.9, -33.6)-43 (-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 35.510.2 (1.9, 12.3)11.2 (8.3, 20.5)RLP-C 82-56.4 (-67.1, -49)-64.9 (-74, -56.6)Apo-E 16-42.9 (-46.3, -33.3)-42.5 (-47.1, -35.6)

14.3 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 20 mg 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.

16 How Supplied/Storage And Handling

Rosuvastatin capsules 5 mg are hard gelatin capsule, Size “3” pink cap/off white body, imprinted axially with “984” on cap and body in black ink filled with yellow colored granules. They are available as follows:Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-984-83Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-984-81Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-984-64Rosuvastatin capsules 10 mg are hard gelatin capsule, Size “3” purple cap/off white body, imprinted axially with “985” on cap and body in black ink filled with yellow colored granules. They are available as follows: Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-985-83Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-985-81Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-985-64Rosuvastatin capsules 20 mg are hard gelatin capsule, Size “1” blue cap/off white body, imprinted axially with “986” on cap and body in black ink filled with yellow colored granules. They are available as follows: Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-986-83Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-986-81Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-986-64Rosuvastatin capsules 40 mg are hard gelatin capsule, Size “0el” green cap/white body, imprinted axially with “987” on cap and body in black ink filled with yellow colored granules. They are available as follows: Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-987-83Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-987-81Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-987-64StorageStore rosuvastatin capsules at 20º to 25ºC (68º to 77ºF); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].Protect from moisture.

17 Patient Counseling Information

  • Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).Skeletal Muscle EffectsPatients 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 EZALLOR Sprinkle.Concomitant Use of AntacidsWhen taking EZALLOR Sprinkle with an aluminum and magnesium hydroxide combination antacid, the antacid should be taken at least 2 hours after EZALLOR Sprinkle 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 EZALLOR Sprinkle [see Contraindications (4) and Use in Specific Populations (8.2)].Liver EnzymesIt is recommended that liver enzyme tests be performed before the initiation of EZALLOR Sprinkle and if signs or symptoms of liver injury occur. All patients treated with EZALLOR Sprinkle should be advised to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.Administration Information Inform patients:EZALLOR Sprinkle can be administered as a single dose at any time of day, with or without food. Patients should be instructed not to take 2 doses of EZALLOR Sprinkle within 12 hours of each other.EZALLOR Sprinkle should not be crushed or chewed. For Oral Administration Patients with Difficulty Swallowing CapsulesInstruct patients that the EZALLOR Sprinkle can be opened, the granules filled in the capsule carefully emptied onto one teaspoon of applesauce. The granules with applesauce should be swallowed immediately, without chewing. The mixture should not be stored for future use. If it is not used in its entirety, the remaining mixture should be discarded immediately.For Nasogastric Tube (≥16 French) Administration Instruct patients that EZALLOR Sprinklecan be opened and the intact granules emptied into a 60 mL catheter tipped syringe and add 40 mL of water. Replace the plunger and shake the syringe vigorously for 15 seconds. The granules in rosuvastatin may start dissolving which is acceptable. Attach the syringe to a nasogastric tube (≥16-French) and deliver the contents of the syringe through the nasogastric tube into the stomach. After administering the granules, the nasogastric tube should be flushed with 20 mL of additional water. The mixture must be used immediately after preparation and not be stored for future use. If it is not used in its entirety, the remaining mixture should be discarded immediately. Use with any other liquids is not recommended.

Patient Information

  • EZALLORTM Sprinkle (Ez-Aah-Lor Spr-En-Kle)(rosuvastatin)Capsules, for oral useWhat is EZALLOR Sprinkle?EZALLOR Sprinkle 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. EZALLOR Sprinkle works by reducing cholesterol in two ways: EZALLOR Sprinkle blocks an enzyme in the liver causing the liver to make less cholesterol, and EZALLOR Sprinkle increases the uptake and breakdown by the liver of cholesterol already in the blood. EZALLOR Sprinkle is used in adults along with diet to:lower the level of your “bad” cholesterol (LDL).increase the level of your “good” cholesterol (HDL).lower the level of fat in your blood (triglycerides).EZALLOR Sprinkle is used to treat: adults who cannot control their cholesterol levels by diet and exercise alone.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. It is not known if EZALLOR Sprinkle is safe and effective in people who have Fredrickson Type I and V dyslipidemias (abnormal amounts of fat in the blood).Do not take EZALLOR Sprinkle if you:are allergic to rosuvastatin calcium or any of the ingredients in EZALLOR Sprinkle. See the end of this leaflet for a complete list of ingredients in EZALLOR Sprinkle.have liver problems.are pregnant or think you may be pregnant or are planning to become pregnant. EZALLOR Sprinkle may harm your unborn baby. If you become pregnant, stop taking EZALLOR Sprinkle 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 EZALLOR Sprinkle.are breastfeeding. EZALLOR Sprinkle can pass into your breast milk and may harm your baby.Before taking EZALLOR Sprinkle, tell your doctor about all of your medical conditions, including if you:have unexplained muscle aches or weakness.have or have had kidney problems.have had liver problemsdrink more than 2 glasses of alcohol daily.have thyroid problems.are 65 years of age or older.are of Asian descent.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 EZALLOR Sprinkle with certain other medicines may affect each other causing side effects. EZALLOR Sprinkle may affect the way other medicines work, and other medicines may affect how EZALLOR Sprinkle 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 acidfibric 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 EZALLOR Sprinkle?Take EZALLOR Sprinkle exactly as your doctor tells you to take it.Take EZALLOR Sprinkle, by mouth, 1 time each day. Swallow the capsule whole.Do not crush or chew EZALLOR Sprinkle. EZALLOR Sprinkle can be taken at any time of day, with or without food.If you have trouble swallowing a whole capsule, you can open the capsule and take the contents with applesauce. See the “Instructions for Use” at the end of this Patient Package Information for instructions on how to take EZALLOR Sprinkle with applesauce. See the “Instructions for Use” at the end of this Patient Package Information for instructions on how to mix and give EZALLOR Sprinkle through a nasogastric tube. Do not change your dose or stop EZALLOR Sprinkle without talking to your doctor.Your doctor may do blood tests to check your cholesterol levels before and during your treatment with EZALLOR Sprinkle. Your doctor may change your dose of EZALLOR Sprinkle if needed.Your doctor may start you on a cholesterol lowering diet before giving you EZALLOR Sprinkle. Stay on this diet when you take EZALLOR Sprinkle.Wait at least 2 hours after taking EZALLOR Sprinkle to take an antacid that contains a combination of aluminum and magnesium hydroxide.If you miss a dose of EZALLOR Sprinkle, take it as soon as you remember. Do not take 2 doses of EZALLOR Sprinkle within 12 hours of each other.If you take too much EZALLOR Sprinkle or overdose, call your doctor or go to the nearest hospital emergency room right away.What are the possible side effects of EZALLOR Sprinkle?EZALLOR Sprinkle 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:you have unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel more tired than usual, while you take EZALLOR Sprinkle.you have muscle problems that do not go away even after your doctor has told you to stop taking EZALLOR Sprinkle. Your doctor may do further tests to diagnose the cause of your muscle problems.Your chances of getting muscle problems are higher if you:are taking certain other medicines while you take EZALLOR Sprinkleare 65 years of age or olderhave thyroid problems (hypothyroidism) that are not controlledhave kidney problemsare taking higher doses of EZALLOR SprinkleLiver problems. Your doctor should do blood tests to check your liver before you start taking EZALLOR Sprinkle and if you have symptoms of liver problems while you take EZALLOR Sprinkle. Call your doctor right away if you have any of the following symptoms of liver problems: feel unusually tired or weakloss of appetiteupper belly paindark urineyellowing of your skin or the whites of your eyesThe most common side effects may include: headache, muscle aches and pains, abdominal (stomach) pain, weakness, and nausea.Additional side effects that have been reported with EZALLOR Sprinkle 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 EZALLOR Sprinkle. 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 EZALLOR Sprinkle?Store EZALLOR Sprinkle at room temperature between 68ºF to 77ºF (20ºC to 25ºC).Store in a dry place. Safely throw away medicine that is out of date or no longer needed.Keep EZALLOR Sprinkle and all medicines out of the reach of children. General Information about the safe and effective use of EZALLOR Sprinkle. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use EZALLOR Sprinkle for a condition for which it was not prescribed. Do not give EZALLOR Sprinkle to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about EZALLOR Sprinkle that is written for health professionals.What are the Ingredients in EZALLOR Sprinkle?Active Ingredient: rosuvastatin as rosuvastatin calciumInactive Ingredients: microcrystalline cellulose, crospovidone, mannitol, magnesium oxide, ferric oxide, sodium citrate, hypromellose, polyethylene glycol 4000, and silicon dioxide.Capsule shell: gelatin, titanium dioxide, water, sodium lauryl sulfate and the following colorants: FD & C Red 40 (5 mg), FD & C Blue 1 (5 mg, 10 mg, 20 mg), D & C Red 28 (5 mg, 10 mg), FD & C Red 3 (20 mg), and FD & C Green 3 (40 mg).The imprinting black ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, purified water, and potassium hydroxide.Distributed by:Sun Pharmaceutical Industries, Inc.Cranbury, NJ 08512 Manufactured by:Sun Pharmaceutical Industries Ltd.Halol-Baroda Highway, Halol-389 350, Gujarat, India. For more information, call 1- 1-800-818-4555. This Patient Information has been approved by the U.S. Food and Drug Administration Version: 12/2018

Instructions For Use

  • EZALLORTM Sprinkle (Ez-Aah-Lor Spr-En-Kle)(rosuvastatin)Capsules, for oral use Taking EZALLOR Sprinkle with applesauce: For people who have difficulty in swallowing capsules, EZALLOR Sprinkle may be given with applesauce as follows:Carefully open the EZALLOR Sprinkle capsule.Sprinkle the granules filled in the capsules on 1 teaspoonful of applesauce.Swallow the applesauce and granules mixture right away.  Do not chew the granules.Do not save the applesauce and granules mixture for later use. Throw away any remaining applesauce and granules mixture.Giving EZALLOR Sprinkle through a nasogastric tube (NG tube) 16 French or larger, as prescribed by your doctor: For people who have a nasogastric tube in place, EZALLOR Sprinkle may be given as follows:Remove the plunger from 60 mL catheter tipped syringe.Carefully open the EZALLOR Sprinkle capsule and empty the granules into catheter tipped syringe barrel.Add 40 mL of water to the granules that are inside of the catheter tipped syringe barrel. Do not use other liquids.Replace the plunger and shake the catheter tipped syringe well for 15 seconds.Attach the catheter tipped syringe to a nasogastric tube (≥16-French).Give the mixture right away through the nasogastric tube into the stomach. Do not save the mixture for later use. Throw away any remaining mixture.After giving the mixture, the nasogastric tube should be flushed with 20 mL of additional water.How should I store EZALLOR Sprinkle?Store EZALLOR Sprinkle at room temperature between 68ºF to 77ºF (20º C to 25ºF).Store in a dry place.Safely throw away medicine that is out of date or no longer needed.Keep EZALLOR Sprinkle and all medicines out of the reach of children.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Distributed by:Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Manufactured by:Sun Pharmaceutical Industries Ltd. Halol-Baroda Highway, Halol-389 350, Gujarat, India.Version: 12/2018

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