EZALLOR SPRINKLE is indicated: • To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor.

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE is indicated: • To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor." }

• As an adjunct to diet to:   o Reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia.   o Reduce LDL-C and slow the progression of atherosclerosis in adults.   o Reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).

{ "type": "p", "children": [], "text": "• As an adjunct to diet to:   o Reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia.   o Reduce LDL-C and slow the progression of atherosclerosis in adults.   o Reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH)." }

• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH).

{ "type": "p", "children": [], "text": "• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH)." }

• As an adjunct to diet for the treatment of adults with:    o Primary dysbetalipoproteinemia.    o Hypertriglyceridemia.

{ "type": "p", "children": [], "text": "• As an adjunct to diet for the treatment of adults with:    o Primary dysbetalipoproteinemia.    o Hypertriglyceridemia." }

Dosage in Pediatric Patients 8 Years of Age and Older with HeFH

The recommended dosage range is 5 mg to 10 mg orally once daily in patients aged 8 years to less than 10 years and 5 mg to 20 mg orally once daily in patients aged 10 years and older.

Dosage in Pediatric Patients 7 Years of Age and Older with HoFH

The recommended dosage is 20 mg orally once daily.

Initiate EZALLOR SPRINKLE at 5 mg once daily due to increased rosuvastatin plasma concentrations. Consider the risks and benefits of EZALLOR SPRINKLE when treating Asian patients not adequately controlled at doses up to 20 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.3)].

In patients with severe renal impairment (CLcr less than 30 mL/min/1.73 m2) not on hemodialysis, the recommended starting dosage is 5 mg once daily and should not exceed 10 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.

Table 1 displays dosage modifications for EZALLOR SPRINKLE due to drug interactions [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

Table 1: EZALLOR SPRINKLE Dosage Modifications Due to Drug Interactions

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="669.655"> <colgroup> <col width="50%"/> <col width="50%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="center" class="Lrule Rrule" valign="top"><span class="Bold">Concomitantly Used Drug</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">EZALLOR</span><span class="Bold"> SPRINKLE Dosage Modifications</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Cyclosporine</td><td align="justify" class="Rrule" valign="top">Do not exceed 5 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Teriflunomide</td><td align="justify" class="Rrule" valign="top">Do not exceed 10 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Enasidenib</td><td align="justify" class="Rrule" valign="top">Do not exceed 10 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Capmatinib</td><td align="justify" class="Rrule" valign="top">Do not exceed 10 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Fostamatinib</td><td align="justify" class="Rrule" valign="top">Do not exceed 20 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Febuxostat</td><td align="justify" class="Rrule" valign="top">Do not exceed 20 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Gemfibrozil</td><td align="justify" class="Rrule" valign="top">Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Tafamidis</td><td align="justify" class="Rrule" valign="top">Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 20 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" colspan="2" valign="top">Antiviral Medications</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"> <ul class="Disc"> <li>Sofosbuvir/velpatasvir/voxilaprevir</li> <li>Ledipasvir/sofosbuvir</li> </ul> </td><td align="justify" class="Rrule" valign="top">Concomitant use not recommended.</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"> <ul class="Disc"> <li>Simeprevir</li> <li>Dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>Elbasvir/Grazoprevir</li> <li>Sofosbuvir/Velpatasvir</li> <li>Glecaprevir/Pibrentasvir</li> <li>Atazanavir/Ritonavir</li> <li>Lopinavir/Ritonavir</li> </ul> </td><td align="justify" class="Rrule" valign="top">Initiate at 5 mg once daily. Do not exceed 10 mg once daily.</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Darolutamide</td><td align="justify" class="Rrule" valign="top">Do not exceed 5 mg once daily.</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">Regorafenib</td><td align="justify" class="Rrule" valign="top">Do not exceed 10 mg once daily.</td> </tr> </tbody> </table></div>

EZALLOR SPRINKLE capsule should be swallowed whole. For patients unable to swallow an intact capsule, consider the following instructions based on the route of administration and refer to the accompanying Instructions for Use for complete administration instructions: 

Oral Administration

Nasogastric Tube (≥16 French) Administration

Hard gelatin capsules:

{ "type": "p", "children": [], "text": "Hard gelatin capsules: " }

{ "type": "ul", "children": [ "5 mg: 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: 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: 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: Size “0el” green cap/white body, imprinted axially with “987” on cap and body in black ink filled with yellow colored granules." ], "text": "" }

EZALLOR SPRINKLE is contraindicated in patients with:

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE is contraindicated in patients with:" }

{ "type": "ul", "children": [ "Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3)].\n", "Hypersensitivity to rosuvastatin or any excipients in EZALLOR SPRINKLE. Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, have been reported with EZALLOR SPRINKLE [see Adverse Reactions (6.1)]." ], "text": "" }

EZALLOR SPRINKLE may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including EZALLOR SPRINKLE.

Risk Factors for Myopathy

Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher EZALLOR SPRINKLE dosage. Asian patients on EZALLOR SPRINKLE may be at higher risk for myopathy [see Drug Interactions (7.1) and Use in Specific Populations (8.8)]. The myopathy risk is greater in patients taking EZALLOR SPRINKLE 40 mg daily compared with lower EZALLOR SPRINKLE dosages.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis

The concomitant use of EZALLOR SPRINKLE with cyclosporine or gemfibrozil is not recommended. EZALLOR SPRINKLE dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [see Dosage and Administration (2.6)]. Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions (7.1)].

Discontinue EZALLOR SPRINKLE if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if EZALLOR SPRINKLE is discontinued. Temporarily discontinue EZALLOR SPRINKLE in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the EZALLOR SPRINKLE dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue EZALLOR SPRINKLE if IMNM is suspected.

Increases in serum transaminases have been reported with use of EZALLOR SPRINKLE [see Adverse Reactions (6.1)]. In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to more than three times the ULN occurred in 1.1% of patients taking EZALLOR SPRINKLE versus 0.5% of patients treated with placebo. Marked persistent increases of hepatic transaminases have also occurred with EZALLOR Sprinkle. There have been rare postmarketing reports  of fatal and non-fatal hepatic failure in patients taking statins, including EZALLOR SPRINKLE.

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)].

Consider liver enzyme testing before EZALLOR SPRINKLE initiation and when clinically indicated thereafter. EZALLOR SPRINKLE is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)]. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue EZALLOR SPRINKLE.

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 statins, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, consider a dose reduction for patients on EZALLOR SPRINKLE therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.

Increases in HbA1c and fasting serum glucose levels have been reported with statins, including EZALLOR SPRINKLE. Based on clinical trial data with EZALLOR SPRINKLE, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus [see Adverse Reactions (6.1)]. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. 

Adverse reactions reported in ≥ 2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 2. These studies had a treatment duration of up to 12 weeks.

Table 2: Adverse Reactions Reported in ≥ 2% of Patients Treated with Rosuvastatin and > Placebo in Placebo-Controlled Trials

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="704.102"> <colgroup> <col width="13.6475255005667%"/> <col width="14.4408764639214%"/> <col width="14.4408764639214%"/> <col width="14.0158670192671%"/> <col width="14.0158670192671%"/> <col width="14.0158670192671%"/> <col width="15.4231205137892%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td class="Lrule Rrule" valign="top"><span class="Bold">Adverse Reactions</span></td><td align="center" class="Rrule" valign="top"> <br/> <span class="Bold">Placebo<br/> N=382<br/> %</span></td><td align="center" class="Rrule" valign="top"> <p class="First"> <span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">5 mg</span> <br/> <span class="Bold">N=291</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First"> <span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">10 mg</span> <br/> <span class="Bold">N=283</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First"> <span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">20 mg</span> <br/> <span class="Bold">N=64</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First"> <span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">40 mg</span> <br/> <span class="Bold">N=106</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First"> <span class="Bold">Total Rosuvastatin</span> <br/> <span class="Bold">5 mg to 40 mg</span> <br/> <span class="Bold">N=744</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Headache</td><td align="center" class="Rrule" valign="top">5</td><td align="center" class="Rrule" valign="top">5.5</td><td align="center" class="Rrule" valign="top">4.9</td><td align="center" class="Rrule" valign="top">3.1</td><td align="center" class="Rrule" valign="top">8.5</td><td align="center" class="Rrule" valign="top">5.5</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Nausea</td><td align="center" class="Rrule" valign="top">3.1</td><td align="center" class="Rrule" valign="top">3.8</td><td align="center" class="Rrule" valign="top">3.5</td><td align="center" class="Rrule" valign="top">6.3</td><td align="center" class="Rrule" valign="top">0</td><td align="center" class="Rrule" valign="top">3.4</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Myalgia</td><td align="center" class="Rrule" valign="top">1.3</td><td align="center" class="Rrule" valign="top">3.1</td><td align="center" class="Rrule" valign="top">2.1</td><td align="center" class="Rrule" valign="top">6.3</td><td align="center" class="Rrule" valign="top">1.9</td><td align="center" class="Rrule" valign="top">2.8</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Asthenia</td><td align="center" class="Rrule" valign="top"> 2.6</td><td align="center" class="Rrule" valign="top">2.4</td><td align="center" class="Rrule" valign="top">3.2</td><td align="center" class="Rrule" valign="top">4.7</td><td align="center" class="Rrule" valign="top">0.9</td><td align="center" class="Rrule" valign="top">2.7</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Constipation</td><td align="center" class="Rrule" valign="top">2.4</td><td align="center" class="Rrule" valign="top">2.1</td><td align="center" class="Rrule" valign="top">2.1</td><td align="center" class="Rrule" valign="top">4.7</td><td align="center" class="Rrule" valign="top">2.8</td><td align="center" class="Rrule" valign="top">2.4</td> </tr> </tbody> </table></div>

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; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.

In the METEOR study, patients were treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years. Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 3.

Table 3: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in the METEOR Trial

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="663.3375"> <colgroup> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="middle"><span class="Bold">Adverse Reactions</span></td><td align="center" class="Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo<br/> N=281</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="middle"> <p class="First"> <span class="Bold">Rosuvastatin 40 mg</span> <br/> <span class="Bold">N=700</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Myalgia</td><td align="center" class="Rrule" valign="middle"> <br/> 12.1</td><td align="center" class="Rrule" valign="middle">12.7</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Arthralgia</td><td align="center" class="Rrule" valign="middle"> <br/> 7.1</td><td align="center" class="Rrule" valign="middle">10.1</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Headache</td><td align="center" class="Rrule" valign="middle"> <br/> 5.3</td><td align="center" class="Rrule" valign="middle">6.4</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Dizziness</td><td align="center" class="Rrule" valign="middle"> <br/> 2.8</td><td align="center" class="Rrule" valign="middle">4</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Increased CPK</td><td align="center" class="Rrule" valign="middle"> <br/> 0.7</td><td align="center" class="Rrule" valign="middle">2.6</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Abdominal pain</td><td align="center" class="Rrule" valign="middle"> <br/> 1.8</td><td align="center" class="Rrule" valign="middle">2.4</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="middle">ALT greater than 3x ULN<span class="Italics"><span class="Sup">1</span></span></td><td align="center" class="Rrule" valign="middle"> <br/> 0.7</td><td align="center" class="Rrule" valign="middle">2.2</td> </tr> </tbody> </table></div>

1Frequency recorded as abnormal laboratory value.

In the JUPITER study, patients were treated with rosuvastatin 20 mg (n=8,901) or placebo (n=8,901) for a mean duration of 2 years. In JUPITER, 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 Clinical Studies (14)].

Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 4.

Table 4: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in the JUPITER Trial

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="669.123"> <colgroup> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="middle"><span class="Bold">Adverse Reactions</span></td><td align="center" class="Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo<br/> N=8,901</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule" valign="middle"> <p class="First"> <span class="Bold">Rosuvastatin 20 mg</span> <br/> <span class="Bold">N=8,901</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Myalgia</td><td align="center" class="Rrule" valign="middle"> <br/> 6.6</td><td align="center" class="Rrule" valign="middle">7.6</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Arthralgia</td><td align="center" class="Rrule" valign="middle"> <br/> 3.2</td><td align="center" class="Rrule" valign="middle">3.8</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Constipation</td><td align="center" class="Rrule" valign="middle"> <br/> 3</td><td align="center" class="Rrule" valign="middle">3.3</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Diabetes mellitus</td><td align="center" class="Rrule" valign="middle"> <br/> 2.3</td><td align="center" class="Rrule" valign="middle">2.8</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="middle">Nausea</td><td align="center" class="Rrule" valign="middle"> <br/> 2.3</td><td align="center" class="Rrule" valign="middle">2.4</td> </tr> </tbody> </table></div>

Pediatric Patients with HeFH

In a 12-week controlled study in pediatric patients 10 to 17 years of age with HeFH with rosuvastatin 5 mg to 20 mg daily [see Use in Specific Populations (8.4) and Clinical Studies (14)], elevations in serum CK greater than 10 x ULN were observed more frequently in rosuvastatin-treated patients compared with patients receiving placebo. Four of 130 (3%) patients treated with rosuvastatin (2 treated with 10 mg and 2 treated with 20 mg) had increased CK greater than 10 x ULN, compared to 0 of 46 patients on placebo.

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

Blood Disorders: thrombocytopenia

Hepatobiliary Disorders: hepatitis, jaundice, fatal and non-fatal hepatic failure

Musculoskeletal Disorders: arthralgia, rare reports of immune-mediated necrotizing myopathy associated with statin use

Nervous System Disorders: peripheral neuropathy, rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, and confusion) associated with the use of 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). There have been rare reports of new-onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered.

Psychiatric Disorders: depression, sleep disorders (including insomnia and nightmares)

Reproductive System and Breast Disorders: gynecomastia

Respiratory Disorders: interstitial lung disease

Skin and Subcutaneous Tissue Disorders: drug reaction with eosinophilia and systemic symptoms (DRESS), lichenoid drug eruption

Rosuvastatin is a substrate of CYP2C9 and transporters (such as OATP1B1, BCRP). Rosuvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP2C9 and transporters. Table 5 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with EZALLOR SPRINKLE and instructions for preventing or managing them [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Table 5: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with EZALLOR SPRINKLE

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="633px"> <tbody class="Headless"> <tr class="First"> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">C</span><span class="Bold">yclosporine</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">If used concomitantly, do not exceed a dose of EZALLOR SPRINKLE 5 mg once daily<span class="Italics">. </span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Teriflunomide</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Teriflunomide increased rosuvastatin exposure more than 2.5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking teriflunomide, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Enasidenib</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Enasidenib increased rosuvastatin exposure more than 2.4-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking enasidenib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">C</span><span class="Bold">apmatinib</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Capmatinib increased rosuvastatin exposure more than 2.1-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking capmatinib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">F</span><span class="Bold">ostamatinib</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Fostamatinib increased rosuvastatin exposure more than 2-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking fostamatinib, do not exceed a dose of EZALLOR SPRINKLE 20 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Fe</span><span class="Bold">buxostat</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Febuxostat increased rosuvastatin exposure more than 1.9-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking febuxostat, do not exceed a dose of EZALLOR SPRINKLE 20 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Gemfibrozil</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Avoid concomitant use of gemfibrozil with EZALLOR SPRINKLE. If used concomitantly, initiate EZALLOR SPRINKLE at 5 mg once daily and do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Tafamidis</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Tafamidis significantly increased rosuvastatin exposure and tafamidis may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of tafamidis with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Avoid concomitant use of tafamidis with EZALLOR SPRINKLE. If used concomitantly, initiate EZALLOR SPRINKLE at 5 mg once daily and do not exceed a dose of EZALLOR SPRINKLE 20 mg once daily. Monitor for signs of myopathy and rhabdomyolysis if used concomitantly with EZALLOR SPRINKLE<span class="Italics">. </span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">A</span><span class="Bold">n</span><span class="Bold">t</span><span class="Bold">i-Vi</span><span class="Bold">r</span><span class="Bold">a</span><span class="Bold">l Medications</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td valign="top"> <ul> <li>Sofosbuvir/velpatasvir/voxilaprevir</li> <li>Ledipasvir/sofosbuvir</li> </ul> </td><td valign="top"> <p class="First First TableParagraph">Avoid concomitant use with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"></td><td valign="top"> <ul> <li>Simeprevir</li> <li>Dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>Elbasvir/grazoprevir</li> <li>Sofosbuvir/velpatasvir</li> <li>Glecaprevir/pibrentasvir</li> <li>Atazanavir/ritonavir</li> <li>Lopinavir/ritonavir</li> </ul> </td><td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph">Initiate with EZALLOR SPRINKLE 5 mg</p> <p class="TableParagraph">once daily, and do not exceed a dose of EZALLOR SPRINKLE 10</p> <p class="TableParagraph">mg once daily.</p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">D</span><span class="Bold">arolutamide</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use<span class="Italics">.</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking darolutamide, do not exceed a dose of EZALLOR SPRINKLE 5 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Re</span><span class="Bold">gorafenib</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking regorafenib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily<span class="Italics">.</span> </p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Fe</span><span class="Bold">nofibrates (e.g., fenofibrate and fenofibric acid)</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with EZALLOR SPRINKLE</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Consider if the benefit of using fibrates concomitantly with EZALLOR SPRINKLE outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">N</span><span class="Bold">iacin</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Cases of myopathy and rhabdomyolysis have occurred with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Consider if the benefit of using lipid-modifying doses (≥1 g/day) of niacin concomitantly with EZALLOR SPRINKLE outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">C</span><span class="Bold">olchicine</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with EZALLOR SPRINKLE.</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"></p> <p class="TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Consider if the benefit of using colchicine concomitantly with EZALLOR SPRINKLE outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</p> </td> </tr> <tr> <td colspan="3" valign="top"> <p class="First First TableParagraph"> <span class="Bold">Ticagrelor</span> </p> </td> </tr> <tr> <td> <p class="First First TableParagraph"> <span class="Italics">Clinical Impact:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">Concomitant use of EZALLOR SPRINKLE and ticagrelor has been shown to increase rosuvastatin concentrations, which may result in increased risk of myopathy. Cases of myopathy and rhabdomyolysis have been reported in patients using both products concomitantly. Cases have occurred more frequently in patients taking 40 mg of rosuvastatin.</p> </td> </tr> <tr class="Last"> <td> <p class="First First TableParagraph"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td colspan="2" valign="top"> <p class="First First TableParagraph">In patients taking concomitant ticagrelor, especially those with additional risk factors for myopathy and rhabdomyolysis, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of EZALLOR SPRINKLE.</p> </td> </tr> </tbody> </table></div>

Table 6 presents drug interactions that may decrease the efficacy of EZALLOR SPRINKLE and instructions for preventing or managing them.

Table 6: Drug Interactions that Decrease the Efficacy of EZALLOR SPRINKLE

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="661"> <colgroup> <col width="21.7939663000706%"/> <col width="78.2060336999294%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold"> A</span><span class="Bold">ntacids</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"> <br/> <span class="Italics">Clinical Impact:</span></td><td align="justify" class="Rrule" valign="top">Concomitant aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% <span class="Italics">[see Clinical Pharmacology (12.3)]</span>.</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top"> <br/> <span class="Italics"> I</span><span class="Italics">ntervention:</span></td><td align="justify" class="Rrule" valign="top">In patients taking antacid, administer EZALLOR SPRINKLE at least 2 hours before the antacid.</td> </tr> </tbody> </table></div>

Table 7 presents EZALLOR SPRINKLE effect on other drugs and instructions for preventing or managing them.

Table 7: Rosuvastatin Effects on Other Drugs

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="661"> <colgroup> <col width="21.7939663000706%"/> <col width="78.2060336999294%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Warfarin</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"> <br/> <span class="Italics">Clinical Impact:</span></td><td class="Rrule" valign="top">Rosuvastatin significantly increased the INR in patients receiving warfarin<span class="Italics"> [see Clinical Pharmacology (12.3)]</span>.</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top"> <br/> <br/> <span class="Italics"> I</span><span class="Italics">ntervention:</span></td><td align="justify" class="Rrule" valign="top">In patients taking warfarin, obtain an INR before starting EZALLOR SPRINKLE and frequently enough after initiation, dose titration or discontinuation to ensure that no significant alteration in INR occurs. Once the INR is stable, monitor INR at regularly recommended intervals.</td> </tr> </tbody> </table></div>

Risk Summary

Discontinue EZALLOR SPRINKLE when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient.

EZALLOR SPRINKLE decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, EZALLOR SPRINKLE may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients.

Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with rosuvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data).

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (MRHD) of 40 mg/day, based on AUC and body surface area (mg/m2), respectively (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls

did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy,

after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly preexisting diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.

Animal Data

In female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the MRHD dose of 40 mg/day based on AUC).

In pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the MRHD of 40 mg/day based body surface area).

In pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area).

Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. In rabbits, fetal tissue distribution was 25% of maternal plasma concentration  after a single oral gavage dose of 1 mg/kg on gestation day 18.

Risk Summary

Limited data from case reports in published literature indicate that 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. Statins, including EZALLOR SPRINKLE, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant.

Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with EZALLOR SPRINKLE [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.1)].

The safety and effectiveness of rosuvastatin as an adjunct to diet to reduce LDL-C have been established in pediatric patients 8 years of age and older with HeFH. Use of rosuvastatin for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with HeFH and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with HeFH [see Clinical Studies (14)]. In the 1-year trial with a 12-week controlled phase, there was no detectable effect of rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in patients aged 10 to 17 years.

The safety and effectiveness of rosuvastatin as an adjunct to other LDL-C-lowering therapies to reduce LDL-C have been established in pediatric patients 7 years of age and older with HoFH. Use of rosuvastatin for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with HoFH [see Clinical Studies (14)].

The safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with HeFH, younger than 7 years of age with HoFH, or in pediatric patients with other types of hyperlipidemia (other than HeFH or HoFH).

Of the 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.

Advanced age (≥65 years) is a risk factor for rosuvastatin-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving EZALLOR SPRINKLE for the increased risk of myopathy [see Warnings and Precautions (5.1)].

Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥ 30 mL/min/1.73 m2). Exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) who are not receiving hemodialysis [see Clinical Pharmacology (12.3)].

Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. In patients with severe renal impairment not on hemodialysis, the recommended starting dosage is 5 mg daily and should not exceed 10 mg daily [see Dosage and Administration (2.5) and Warnings and Precautions (5.1)].

EZALLOR SPRINKLE is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Contraindications (4), Warning and Precautions (5.3) and Clinical Pharmacology (12.3)].

Pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects when compared with White controls. Adjust the EZALLOR SPRINKLE dosage in Asian patients [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

No specific antidotes for rosuvastatin are known. Hemodialysis does not significantly enhance clearance of rosuvastatin. In the event of overdose, consider contacting the Poison Help line (1- 800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

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Rosuvastatin calcium is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)-reductase inhibitor.

{ "type": "p", "children": [], "text": "Rosuvastatin calcium is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)-reductase inhibitor." }

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.

{ "type": "p", "children": [], "text": "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:\n\n\n 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 use 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: crospovidone, ferric oxide, hypromellose, magnesium oxide, mannitol, microcrystalline cellulose, polyethylene glycol 4000, silicon dioxide, and sodium citrate. The capsule shells have the following inactive ingredients: gelatin, sodium lauryl sulfate, titanium dioxide, and water. 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 black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.

{ "type": "p", "children": [], "text": "Each rosuvastatin capsule for oral use 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: crospovidone, ferric oxide, hypromellose, magnesium oxide, mannitol, microcrystalline cellulose, polyethylene glycol 4000, silicon dioxide, and sodium citrate. The capsule shells have the following inactive ingredients: gelatin, sodium lauryl sulfate, titanium dioxide, and water. 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 black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution." }

Rosuvastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol.

Inhibition of HMG-CoA reductase by rosuvastatin accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins. The maximum LDL-C reduction of rosuvastatin is usually achieved by 4 weeks and is maintained after that.

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 dose. The absolute bioavailability of rosuvastatin is approximately 20%. The AUC of rosuvastatin does not differ following evening or morning drug administration.

Effect of food

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

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.

Elimination

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%).

After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route. The elimination half-life of rosuvastatin is approximately 19 hours.

Specific Populations

Geriatric Patients

There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥ 65 years).

Pediatric Patients

In a population pharmacokinetic analysis of two pediatric trials involving patients with HeFH 10 to 17 years of age and 8 to 17 years of age, respectively, rosuvastatin exposure appeared comparable to or lower than rosuvastatin exposure in adult patients.

Male and Female Patients

There were no differences in plasma concentrations of rosuvastatin between males and females.

Racial or Ethnic Groups     

A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among White, Hispanic or Latino ethnicity, 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 White control group.

Patients with 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).

Steady-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 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 Interaction Studies

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 with medications that are inhibitors of these transporter proteins (e.g., cyclosporine, certain HIV protease inhibitors [see Dosage and Administration (2.6) and Drug Interactions (7.1)] and ticagrelor [see Drug Interactions (7.1)]) may result in increased rosuvastatin plasma concentrations. 

Table 8: Effect of Coadministered Drugs on Rosuvastatin Systemic Exposure

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="665"> <colgroup> <col width="36.6151995187487%"/> <col width="20.8341688389814%"/> <col width="21.3956286344496%"/> <col width="21.1550030078203%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"><span class="Bold">Coadministered drug and dosing regimen</span> <br/> </td><td align="center" class="Rrule" colspan="3" valign="middle"><span class="Bold">Rosuvastatin</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Mean Ratio (ratio with/without coadministered drug) No Effect = 1</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose (mg)<span class="Sup">1</span></span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Change in AUC</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Change in C<span class="Sub">max</span></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Sofosbuvir/velpatasvir/voxilaprevir (400 mg/100 mg/100 mg) + Voxilaprevir (100 mg) once daily for 15 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="middle">7.39<span class="Sup">2</span> <br/>(6.68 to 8.18) <span class="Sup">3</span> <br/> <br/> </td><td align="center" class="Rrule" valign="middle">18.88<span class="Sup">2</span> <br/>(16.23 to 21.96) <span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Cyclosporine - stable dose required<br/>(75 mg to 200 mg BID)<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, QD for 10 days<br/> <br/> </td><td align="center" class="Rrule" valign="middle">7.1<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="middle">11<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Darolutamide 600 mg BID, 5 days <br/> </td><td align="center" class="Rrule" valign="middle">5 mg, single dose<br/> </td><td align="center" class="Rrule" valign="middle">5.2<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="middle">~5<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Regorafenib 160 mg QD, 14 days <br/> </td><td align="center" class="Rrule" valign="middle">5 mg, single dose<br/> </td><td align="center" class="Rrule" valign="middle">3.8<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="middle">4.6<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Atazanavir/ritonavir combination <br/>300 mg/100 mg QD for 8 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">3.1<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="middle">7<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Simeprevir 150 mg QD, 7 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="middle">2.8<span class="Sup">2</span> <br/>(2.3 to 3.4)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">3.2<span class="Sup">2</span> <br/>(2.6 to 3.9)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Velpatasvir 100 mg once daily<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="top">2.69<span class="Sup">2</span> <br/>(2.46 to 2.94) <span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="top">2.61<span class="Sup">2</span> <br/>(2.32 to 2.92)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Ombitasvir 25 mg/paritaprevir 150 mg/ ritonavir 100 mg + dasabuvir 400 mg BID <br/> </td><td align="center" class="Rrule" valign="middle">5 mg, single dose <br/> </td><td align="center" class="Rrule" valign="middle">2.59<span class="Sup">2</span> <br/> (2.09 to 3.21) <span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">7.13<span class="Sup">2</span> <br/> (5.11 to 9.96)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Teriflunomide <br/> </td><td class="Rrule" valign="middle">    Not available <br/> </td><td align="center" class="Rrule" valign="middle">2.51<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="middle">2.65<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Enasidenib 100 mg QD, 28 days <br/> </td><td class="Rrule" valign="middle">10 mg, single dose <br/> </td><td align="center" class="Rrule" valign="middle">2.44<br/> </td><td align="center" class="Rrule" valign="middle">3.66<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Elbasvir 50 mg/grazoprevir 200mg once daily <br/> </td><td align="center" class="Rrule" valign="middle">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="top">2.26<span class="Sup">2 </span> <br/>(1.89 to 2.69) <span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="top">5.49<span class="Sup">2</span> <br/>(4.29 to 7.04)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Glecaprevir 400 mg/pibrentasvir 120 mg once daily <br/> </td><td align="center" class="Rrule" valign="middle">5 mg, once daily <br/> </td><td align="center" class="Rrule" valign="top">2.15<span class="Sup">2 </span> <br/>(1.88 to 2.46) <span class="Sup">3 </span> <br/> </td><td align="center" class="Rrule" valign="top">5.62<span class="Sup">2 </span> <br/>(4.80 to 6.59)<span class="Sup">3 </span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Lopinavir/ritonavir combination <br/>400 mg/100 mg BID for 17 days<br/> </td><td align="center" class="Rrule" valign="middle">20 mg, QD for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">2.1<span class="Sup">2</span> <br/>(1.7 to 2.6)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">5<span class="Sup">2</span> <br/>(3.4 to 6.4)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Capmatinib 400 mg BID<br/> </td><td align="center" class="Rrule" valign="top">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="top">2.08<span class="Italics"><span class="Sup">2</span></span> <br/>(1.56 to 2.76) <span class="Italics"><span class="Sup">3</span></span> <br/> </td><td align="center" class="Rrule" valign="top">3.04<span class="Italics"><span class="Sup">2</span></span> <br/>(2.36 to 3.92)<span class="Italics"><span class="Sup">3</span></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Fostamatinib 100 mg BID<br/> </td><td align="center" class="Rrule" valign="top">20 mg, single dose<br/> </td><td align="center" class="Rrule" valign="top">1.96<span class="Italics"><span class="Sup">2</span></span> <br/>(1.77 to 2.15) <span class="Italics"><span class="Sup">3</span></span> <br/> </td><td align="center" class="Rrule" valign="top">1.88<span class="Italics"><span class="Sup">2</span></span> <br/>(1.69 to 2.09)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Febuxostat 120 mg QD for 4 days<br/> </td><td align="center" class="Rrule" valign="top">10 mg, single dose<br/> </td><td align="center" class="Rrule" valign="top">1.9<span class="Sup">2</span> <br/>(1.5 to 2.5) <span class="Italics"><span class="Sup">3</span></span> <br/> </td><td align="center" class="Rrule" valign="top">2.1<span class="Sup">2</span> <br/>(1.8 to 2.6)<span class="Italics"><span class="Sup">3</span></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Gemfibrozil 600 mg BID for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">80 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.9<span class="Sup">2</span> <br/>(1.6 to 2.2)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">2.2<span class="Sup">2</span> <br/>(1.8 to 2.7)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Tafamidis 61 mg BID on Days 1 &amp; 2, followed by QD on Days 3 to 9<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="top">1.97<span class="Sup">2</span> <br/>(1.68 to 2.31)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="top">1.86<span class="Sup">2</span> <br/>(1.59 to 2.16)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Eltrombopag 75 mg QD, 5 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.6 <br/>(1.4 to 1.7)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">2 <br/>(1.8 to 2.3)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Darunavir 600 mg/ritonavir 100 mg BID, 7 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, QD for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">1.5 <br/>(1 to 2.1)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">2.4 <br/>(1.6 to 3.6)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Tipranavir/ritonavir combination 500 mg/200 mg BID for 11 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.4 <br/>(1.2 to 1.6)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">2.2 <br/>(1.8 to 2.7)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Dronedarone 400 mg BID<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.4<br/> </td><td align="center" class="Rrule" valign="middle"> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Itraconazole 200 mg QD, 5 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg or 80 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.4 <br/>(1.2 to 1.6)<span class="Sup">3</span> <br/>1.3 <br/>(1.1 to 1.4)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">1.4 <br/>(1.2 to 1.5)<span class="Sup">3</span> <br/>1.2 <br/>(0.9 to 1.4)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Ezetimibe 10 mg QD, 14 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg, QD for 14 days<br/> </td><td align="center" class="Rrule" valign="middle">1.2 <br/>(0.9 to 1.6)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">1.2<br/>(0.8 to 1.6)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Fosamprenavir/ritonavir 700 mg/100 mg BID for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.1<br/> </td><td align="center" class="Rrule" valign="middle">1.5<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Fenofibrate 67 mg TID for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">10 mg<br/> </td><td align="center" class="Rrule" valign="middle">↔<br/> </td><td align="center" class="Rrule" valign="middle">1.2 <br/>(1.1 to 1.3)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Rifampicin 450 mg QD, 7 days<br/> </td><td align="center" class="Rrule" valign="middle">20 mg<br/> </td><td align="center" class="Rrule" valign="middle">↔<br/> </td><td align="center" class="Rrule" valign="middle"> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Aluminum &amp; magnesium hydroxide combination antacid<br/>Administered simultaneously<br/> <br/>Administered 2 hours apart<br/> </td><td align="center" class="Rrule" valign="middle"> <br/> <br/>40 mg<br/> <br/>40 mg<br/> </td><td align="center" class="Rrule" valign="middle"> <br/> <br/>0.5<span class="Sup">2</span> <br/>(0.4 to 0.5)<span class="Sup">3</span> <br/>0.8<br/>(0.7 to 0.9)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle"> <br/> <br/>0.5<span class="Sup">2</span> <br/>(0.4 to 0.6)<span class="Sup">3</span> <br/>0.8 <br/>(0.7 to 1)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Ketoconazole 200 mg BID for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">80 mg<br/> </td><td align="center" class="Rrule" valign="middle">1<br/>(0.8 to 1.2)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">1<br/>(0.7 to 1.3)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Fluconazole 200 mg QD for 11 days<br/> </td><td align="center" class="Rrule" valign="middle">80 mg<br/> </td><td align="center" class="Rrule" valign="middle">1.1 <br/>(1 to 1.3)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">1.1<br/>(0.9 to 1.4)<span class="Sup">3</span> <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">Erythromycin 500 mg QID for 7 days<br/> </td><td align="center" class="Rrule" valign="middle">80 mg<br/> </td><td align="center" class="Rrule" valign="middle">0.8 <br/>(0.7 to 0.9)<span class="Sup">3</span> <br/> </td><td align="center" class="Rrule" valign="middle">0.7 <br/>(0.5 to 0.9)<span class="Sup">3</span> <br/> </td> </tr> </tbody> </table></div>

QD= Once daily, BID= Twice daily, TID= Three times daily, QID= Four times daily

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 9: Effect of Rosuvastatin Coadministration on Systemic Exposure to Other Drugs

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="668"> <colgroup> <col width="35.1192257807044%"/> <col width="29.7615484385912%"/> <col width="18.1183278459543%"/> <col width="17.0008979347501%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"><span class="Bold">Rosuvastatin Dosage Regimen</span> <br/> </td><td align="center" class="Rrule" colspan="3" valign="middle"><span class="Bold">Coadministered Drug</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Mean Ratio (ratio with/without coadministered drug) No Effect = 1</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Name and Dose</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Change in AUC</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Change in C<span class="Sub">max</span></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">40 mg QD for 10 days<br/> </td><td align="center" class="Rrule" valign="top">Warfarin<span class="Sup">1</span> <br/>25 mg single dose<br/> </td><td align="center" class="Rrule" valign="top">R-Warfarin <br/>1<br/>(1 to 1.1)<span class="Sup">2</span> <br/>S-Warfarin <br/>1.1 <br/>(1 to 1.1)<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="top">R-Warfarin <br/>1<br/>(0.9 to 1)<span class="Sup">2</span> <br/>S-Warfarin <br/>1 <br/>(0.9 to 1.1)<span class="Sup">2</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">40 mg QD for 12 days <br/> </td><td align="center" class="Rrule" valign="top">Digoxin <br/>0.5 mg single dose<br/> </td><td align="center" class="Rrule" valign="top">1 <br/>(0.9 to 1.2)<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="top">1<br/>(0.9 to 1.2)<span class="Sup">2</span> <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">40 mg QD for 28 days <br/> </td><td align="center" class="Rrule" valign="top">Oral Contraceptive<br/>(ethinyl estradiol 0.035 mg &amp; norgestrel 0.18, 0.215 and 0.25 mg) QD for 21 Days<br/> </td><td align="center" class="Rrule" valign="bottom">EE 1.3<br/>(1.2 to 1.3)<span class="Sup">2</span> <br/>NG 1.3<br/>(1.3 to 1.4)<span class="Sup">2</span> <br/> </td><td align="center" class="Rrule" valign="bottom">EE 1.3 <br/>(1.2 to 1.3)<span class="Sup">2</span> <br/>NG 1.2 <br/>(1.1 to 1.3)<span class="Sup">2</span> <br/> </td> </tr> </tbody> </table></div>

EE = ethinyl estradiol, NG = norgestrel, QD = Once daily

1   Clinically significant pharmacodynamic effects [see Drug Interactions (7.3)]

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)

Disposition of 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.

Carcinogenesis

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.

Mutagenesis

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.

Impairment of Fertility

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.

Primary Prevention of CV Disease

{ "type": "p", "children": [], "text": "\nPrimary Prevention of CV Disease \n" }

In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of rosuvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL-C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Patients had a median baseline LDL-C of 108 mg/dL and hsCRP of 4.3 mg/L. Patients were randomly assigned to placebo (n=8,901) or rosuvastatin 20 mg once daily (n=8,901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects.

{ "type": "p", "children": [], "text": "In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of rosuvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL-C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Patients had a median baseline LDL-C of 108 mg/dL and hsCRP of 4.3 mg/L. Patients were randomly assigned to placebo (n=8,901) or rosuvastatin 20 mg once daily (n=8,901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects." }

The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure.

{ "type": "p", "children": [], "text": "The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure." }

Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see Figure 1). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL-C, HDL-C, and hsCRP levels.

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see Figure 1). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL-C, HDL-C, and hsCRP levels." }

Figure 1. Time to First Occurrence of Major CV Events in JUPITER

{ "type": "p", "children": [], "text": "\nFigure 1. Time to First Occurrence of Major CV Events in JUPITER\n" }

The individual components of the primary end point are presented in Figure 3. Rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to CV causes or hospitalizations for unstable angina.

{ "type": "p", "children": [], "text": "The individual components of the primary end point are presented in Figure 3. Rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to CV causes or hospitalizations for unstable angina." }

Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects).

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects)." }

In a post-hoc subgroup analysis of JUPITER subjects (rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL-C) other than age, after adjustment for high HDL-C, there was no significant treatment benefit with rosuvastatin treatment.

{ "type": "p", "children": [], "text": "In a post-hoc subgroup analysis of JUPITER subjects (rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL-C) other than age, after adjustment for high HDL-C, there was no significant treatment benefit with rosuvastatin treatment." }

Figure 2. Major CV Events by Treatment Group in JUPITER

{ "type": "p", "children": [], "text": "\nFigure 2. Major CV Events by Treatment Group in JUPITER\n" }

At one year, rosuvastatin increased HDL-C and reduced LDL-C, hsCRP, total cholesterol and serum triglyceride levels (p<0.001 for all versus placebo).

{ "type": "p", "children": [], "text": "At one year, rosuvastatin increased HDL-C and reduced LDL-C, hsCRP, total cholesterol and serum triglyceride levels (p<0.001 for all versus placebo)." }

Primary Hyperlipidemia in Adults

{ "type": "p", "children": [], "text": "\nPrimary Hyperlipidemia in Adults\n" }

Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia.

{ "type": "p", "children": [], "text": "Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia." }

In a multicenter, double-blind, placebo-controlled study in patients with hyperlipidemia, rosuvastatin given as a single daily dose (5 to 40 mg) for 6 weeks significantly reduced Total-C, LDL-C, non-HDL-C, and ApoB, across the dose range (Table 10).

{ "type": "p", "children": [], "text": "In a multicenter, double-blind, placebo-controlled study in patients with hyperlipidemia, rosuvastatin given as a single daily dose (5 to 40 mg) for 6 weeks significantly reduced Total-C, LDL-C, non-HDL-C, and ApoB, across the dose range (Table 10)." }

Table 10: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Hyperlipidemia (Adjusted Mean % Change from Baseline at Week 6)

{ "type": "p", "children": [], "text": "\nTable 10: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Hyperlipidemia (Adjusted Mean % Change from Baseline at Week 6)\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="674"> <colgroup> <col width="21.796774512714%"/> <col width="6.20362125259721%"/> <col width="11.2001583061245%"/> <col width="12.1499950529336%"/> <col width="12.1796774512714%"/> <col width="12.1994657168299%"/> <col width="12.0807361234788%"/> <col width="12.1895715840507%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">Dose</span></td><td align="justify" class="Rrule" valign="top"><span class="Bold">N </span></td><td align="justify" class="Rrule" valign="top"><span class="Bold">Total-C </span></td><td align="center" class="Rrule" valign="top"><span class="Bold">LDL-C</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Non-HDL-C</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">ApoB</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">TG</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">HDL-C</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Placebo</td><td align="justify" class="Rrule" valign="top">13</td><td align="center" class="Rrule" valign="top">-5</td><td align="center" class="Rrule" valign="top">-7</td><td align="center" class="Rrule" valign="top">-7</td><td align="center" class="Rrule" valign="top">-3</td><td align="center" class="Rrule" valign="top">-3</td><td align="center" class="Rrule" valign="top">3</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Rosuvastatin 5 mg</td><td align="justify" class="Rrule" valign="top">17</td><td align="center" class="Rrule" valign="top">-33</td><td align="center" class="Rrule" valign="top">-45</td><td align="center" class="Rrule" valign="top">-44</td><td align="center" class="Rrule" valign="top">-38</td><td align="center" class="Rrule" valign="top">-35</td><td align="center" class="Rrule" valign="top">13</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Rosuvastatin 10 mg</td><td class="Rrule" valign="top">17</td><td align="center" class="Rrule" valign="top">-36</td><td align="center" class="Rrule" valign="top">-52</td><td align="center" class="Rrule" valign="top">-48</td><td align="center" class="Rrule" valign="top">-42</td><td align="center" class="Rrule" valign="top">-10</td><td align="center" class="Rrule" valign="top">14</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Rosuvastatin 20 mg</td><td class="Rrule" valign="top">17</td><td align="center" class="Rrule" valign="top">-40</td><td align="center" class="Rrule" valign="top">-55</td><td align="center" class="Rrule" valign="top">-51</td><td align="center" class="Rrule" valign="top">-46</td><td align="center" class="Rrule" valign="top">-23</td><td align="center" class="Rrule" valign="top">8</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">Rosuvastatin 40 mg</td><td class="Rrule" valign="top">18</td><td align="center" class="Rrule" valign="top">-46</td><td align="center" class="Rrule" valign="top">-63</td><td align="center" class="Rrule" valign="top">-60</td><td align="center" class="Rrule" valign="top">-54</td><td align="center" class="Rrule" valign="top">-28</td><td align="center" class="Rrule" valign="top">10</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"674\">\n<colgroup>\n<col width=\"21.796774512714%\"/>\n<col width=\"6.20362125259721%\"/>\n<col width=\"11.2001583061245%\"/>\n<col width=\"12.1499950529336%\"/>\n<col width=\"12.1796774512714%\"/>\n<col width=\"12.1994657168299%\"/>\n<col width=\"12.0807361234788%\"/>\n<col width=\"12.1895715840507%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Dose</span></td><td align=\"justify\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">N </span></td><td align=\"justify\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Total-C </span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">LDL-C</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Non-HDL-C</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">ApoB</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">TG</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">HDL-C</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Placebo</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">13</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-7</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-7</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-3</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-3</td><td align=\"center\" class=\"Rrule\" valign=\"top\">3</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Rosuvastatin 5 mg</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">17</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-33</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-45</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-44</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-38</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-35</td><td align=\"center\" class=\"Rrule\" valign=\"top\">13</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Rosuvastatin 10 mg</td><td class=\"Rrule\" valign=\"top\">17</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-36</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-52</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-48</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-42</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-10</td><td align=\"center\" class=\"Rrule\" valign=\"top\">14</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Rosuvastatin 20 mg</td><td class=\"Rrule\" valign=\"top\">17</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-40</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-55</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-51</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-46</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-23</td><td align=\"center\" class=\"Rrule\" valign=\"top\">8</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Rosuvastatin 40 mg</td><td class=\"Rrule\" valign=\"top\">18</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-46</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-63</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-60</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-54</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-28</td><td align=\"center\" class=\"Rrule\" valign=\"top\">10</td>\n</tr>\n</tbody>\n</table></div>" }

Rosuvastatin was compared with the statins (atorvastatin, simvastatin, and pravastatin) in a multicenter, open-label, dose-ranging study of 2,240 patients with hyperlipidemia or mixed dyslipidemia. After randomization, patients were treated for 6 weeks with a single daily dose of either rosuvastatin, atorvastatin, simvastatin, or pravastatin (see Figure 3 and Table 11).

{ "type": "p", "children": [], "text": "Rosuvastatin was compared with the statins (atorvastatin, simvastatin, and pravastatin) in a multicenter, open-label, dose-ranging study of 2,240 patients with hyperlipidemia or mixed dyslipidemia. After randomization, patients were treated for 6 weeks with a single daily dose of either rosuvastatin, atorvastatin, simvastatin, or pravastatin (see Figure 3 and Table 11)." }

Figure 3. Percent LDL-C Change by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin at Week 6 in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia

{ "type": "p", "children": [], "text": "\nFigure 3. Percent LDL-C Change by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin at Week 6 in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia\n" }

Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDL-C: 189 mg/dL

{ "type": "p", "children": [], "text": "Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDL-C: 189 mg/dL" }

Table 11: Percent Change in LDL-C by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin From Baseline to Week 6 (LS Mean1) in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia (Sample Sizes Ranging from 156 to 167 Patients Per Group)

{ "type": "p", "children": [], "text": "\nTable 11: Percent Change in LDL-C by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin From Baseline to Week 6 (LS Mean1) in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia (Sample Sizes Ranging from 156 to 167 Patients Per Group)\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="647.5105"> <colgroup> <col width="19.9958919585088%"/> <col width="19.9958919585088%"/> <col width="19.9958919585088%"/> <col width="20.0061620622368%"/> <col width="20.0061620622368%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="top"></td><td align="justify" class="Rrule" colspan="4" valign="top"><span class="Bold">Treatment Daily Dose </span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">Treatment </span></td><td align="center" class="Rrule" valign="top"><span class="Bold">10 mg</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">20 mg</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">40 mg</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">80 mg</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Rosuvastatin</td><td align="center" class="Rrule" valign="top">-46<span class="Sup">2</span></td><td align="center" class="Rrule" valign="top">-52<span class="Sup">3</span></td><td align="center" class="Rrule" valign="top">-55<span class="Sup">4</span></td><td align="center" class="Rrule" valign="middle">---</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Atorvastatin</td><td align="center" class="Rrule" valign="top">-37</td><td align="center" class="Rrule" valign="top">-43</td><td align="center" class="Rrule" valign="top">-48</td><td align="center" class="Rrule" valign="top">-51</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Simvastatin</td><td align="center" class="Rrule" valign="middle">-28</td><td align="center" class="Rrule" valign="middle">-35</td><td align="center" class="Rrule" valign="middle">-39</td><td align="center" class="Rrule" valign="middle">-46</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">Pravastatin</td><td align="center" class="Rrule" valign="top">-20</td><td align="center" class="Rrule" valign="top">-24</td><td align="center" class="Rrule" valign="top">-30</td><td align="center" class="Rrule" valign="middle">---</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"647.5105\">\n<colgroup>\n<col width=\"19.9958919585088%\"/>\n<col width=\"19.9958919585088%\"/>\n<col width=\"19.9958919585088%\"/>\n<col width=\"20.0061620622368%\"/>\n<col width=\"20.0061620622368%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"></td><td align=\"justify\" class=\"Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">Treatment Daily Dose </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Treatment </span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">10 mg</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">20 mg</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">40 mg</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">80 mg</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Rosuvastatin</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-46<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\">-52<span class=\"Sup\">3</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\">-55<span class=\"Sup\">4</span></td><td align=\"center\" class=\"Rrule\" valign=\"middle\">---</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Atorvastatin</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-37</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-48</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-51</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Simvastatin</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">-28</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">-35</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">-39</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">-46</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Pravastatin</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-20</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-24</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-30</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">---</td>\n</tr>\n</tbody>\n</table></div>" }

1 Corresponding standard errors are approximately 1.

{ "type": "p", "children": [], "text": "\n1 Corresponding standard errors are approximately 1." }

2Rosuvastatin 10 mg reduced LDL-C significantly more than atorvastatin 10 mg; pravastatin 10 mg, 20 mg, and 40 mg; simvastatin 10 mg, 20 mg, and 40 mg. (p<0.002)

{ "type": "p", "children": [], "text": "\n2Rosuvastatin 10 mg reduced LDL-C significantly more than atorvastatin 10 mg; pravastatin 10 mg, 20 mg, and 40 mg; simvastatin 10 mg, 20 mg, and 40 mg. (p<0.002)" }

3Rosuvastatin 20 mg reduced LDL-C significantly more than atorvastatin 20 mg and 40 mg; pravastatin 20 mg and 40 mg; simvastatin 20 mg, 40 mg, and 80 mg. (p<0.002)

{ "type": "p", "children": [], "text": "\n3Rosuvastatin 20 mg reduced LDL-C significantly more than atorvastatin 20 mg and 40 mg; pravastatin 20 mg and 40 mg; simvastatin 20 mg, 40 mg, and 80 mg. (p<0.002)" }

4Rosuvastatin 40 mg reduced LDL-C significantly more than atorvastatin 40 mg; pravastatin 40 mg; simvastatin 40 mg, and 80 mg. (p<0.002)

{ "type": "p", "children": [], "text": "\n4Rosuvastatin 40 mg reduced LDL-C significantly more than atorvastatin 40 mg; pravastatin 40 mg; simvastatin 40 mg, and 80 mg. (p<0.002)" }

Slowing of the Progression of Atherosclerosis

{ "type": "p", "children": [], "text": "\nSlowing of the Progression of Atherosclerosis\n" }

In the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR) study, the effect of therapy with rosuvastatin on carotid atherosclerosis was assessed by B-mode ultrasonography in patients with elevated LDL-C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical atherosclerosis as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 adult patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to rosuvastatin 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with rosuvastatin and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, –0.0093; p<0.0001).

{ "type": "p", "children": [], "text": "In the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR) study, the effect of therapy with rosuvastatin on carotid atherosclerosis was assessed by B-mode ultrasonography in patients with elevated LDL-C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical atherosclerosis as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 adult patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to rosuvastatin 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with rosuvastatin and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, –0.0093; p<0.0001)." }

The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p<0.0001). The annualized rate of change from baseline for the group treated with rosuvastatin was -0.0014 mm/year (p=0.32).

{ "type": "p", "children": [], "text": "The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p<0.0001). The annualized rate of change from baseline for the group treated with rosuvastatin was -0.0014 mm/year (p=0.32)." }

At an individual patient level in the group treated with rosuvastatin, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group.

{ "type": "p", "children": [], "text": "At an individual patient level in the group treated with rosuvastatin, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group." }

HeFH in Adults

{ "type": "p", "children": [], "text": "\nHeFH in Adults\n" }

In a study of adult patients with HeFH (baseline mean LDL of 291 mg/dL), patients were randomized to rosuvastatin 20 mg or atorvastatin 20 mg. The dose was increased at 6-week intervals. Significant LDL-C reductions from baseline were seen at each dose in both treatment groups (see Table 12).

{ "type": "p", "children": [], "text": "In a study of adult patients with HeFH (baseline mean LDL of 291 mg/dL), patients were randomized to rosuvastatin 20 mg or atorvastatin 20 mg. The dose was increased at 6-week intervals. Significant LDL-C reductions from baseline were seen at each dose in both treatment groups (see Table 12)." }

Table 12: LDL-C Percent Change from Baseline

{ "type": "p", "children": [], "text": "\nTable 12: LDL-C Percent Change from Baseline\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="647.5105"> <colgroup> <col width="24.997432474068%"/> <col width="24.997432474068%"/> <col width="24.997432474068%"/> <col width="25.007702577796%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="top"></td><td align="justify" class="Rrule" valign="top"></td><td align="justify" class="Rrule" valign="top"><span class="Bold">Rosuvastatin </span><span class="Bold">(n=435) LS Mean</span><span class="Italics"><span class="Sup">1</span></span><span class="Bold">(95% CI) </span></td><td align="justify" class="Rrule" valign="top"><span class="Bold">Atorvastatin (n=187) LS Mean</span><span class="Italics"><span class="Sup">1</span></span><span class="Bold">(95% CI) </span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Week 6</td><td align="justify" class="Rrule" valign="top">20 mg</td><td align="justify" class="Rrule" valign="top">-47% (-49%, -46%)</td><td align="justify" class="Rrule" valign="top">-38% (-40%, -36%)</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Week 12</td><td align="justify" class="Rrule" valign="middle">40 mg</td><td align="justify" class="Rrule" valign="middle">-55% (-57%, -54%)</td><td align="justify" class="Rrule" valign="middle">-47% (-49%, -45%)</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">Week 18</td><td align="justify" class="Rrule" valign="top">80 mg</td><td align="justify" class="Rrule" valign="top">NA</td><td align="justify" class="Rrule" valign="top">-52% (-54%, -50%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"647.5105\">\n<colgroup>\n<col width=\"24.997432474068%\"/>\n<col width=\"24.997432474068%\"/>\n<col width=\"24.997432474068%\"/>\n<col width=\"25.007702577796%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"></td><td align=\"justify\" class=\"Rrule\" valign=\"top\"></td><td align=\"justify\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin </span><span class=\"Bold\">(n=435) LS Mean</span><span class=\"Italics\"><span class=\"Sup\">1</span></span><span class=\"Bold\">(95% CI) </span></td><td align=\"justify\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Atorvastatin (n=187) LS Mean</span><span class=\"Italics\"><span class=\"Sup\">1</span></span><span class=\"Bold\">(95% CI) </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Week 6</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">20 mg</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-47% (-49%, -46%)</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-38% (-40%, -36%)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\">Week 12</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">40 mg</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-55% (-57%, -54%)</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-47% (-49%, -45%)</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Week 18</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">80 mg</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">NA</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-52% (-54%, -50%)</td>\n</tr>\n</tbody>\n</table></div>" }

1 LS Means are least square means adjusted for baseline LDL-C

{ "type": "p", "children": [], "text": "\n1 LS Means are least square means adjusted for baseline LDL-C" }

HeFH in Pediatric Patients

{ "type": "p", "children": [], "text": "\n HeFH in Pediatric Patients\n" }

In a double-blind, randomized, multicenter, placebo-controlled, 12-week study, 176 (97 male and 79 female) pediatric patients with HeFH were randomized to rosuvastatin 5 mg, 10 mg or 20 mg or placebo daily. Patients ranged in age from 10 to 17 years (median age of 14 years) with approximately 30% of the patients 10 to 13 years and approximately 17%, 18%, 40%, and 25% at Tanner stages II, III, IV, and V, respectively. Females were at least 1-year postmenarche. Mean LDL-C at baseline was 233 mg/dL (range of 129 to 399). The 12-week double-blind phase was followed by a 40 week open label dose-titration phase, where all patients (n=173) received 5 mg, 10 mg or 20 mg rosuvastatin daily.

{ "type": "p", "children": [], "text": "In a double-blind, randomized, multicenter, placebo-controlled, 12-week study, 176 (97 male and 79 female) pediatric patients with HeFH were randomized to rosuvastatin 5 mg, 10 mg or 20 mg or placebo daily. Patients ranged in age from 10 to 17 years (median age of 14 years) with approximately 30% of the patients 10 to 13 years and approximately 17%, 18%, 40%, and 25% at Tanner stages II, III, IV, and V, respectively. Females were at least 1-year postmenarche. Mean LDL-C at baseline was 233 mg/dL (range of 129 to 399). The 12-week double-blind phase was followed by a 40 week open label dose-titration phase, where all patients (n=173) received 5 mg, 10 mg or 20 mg rosuvastatin daily." }

Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Results are shown in Table 13 below.

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Results are shown in Table 13 below." }

Table 13: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 10 to 17 years of Age with HeFH (Least-Squares Mean Percent Change from Baseline To Week 12)

{ "type": "p", "children": [], "text": "\nTable 13: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 10 to 17 years of Age with HeFH (Least-Squares Mean Percent Change from Baseline To Week 12)\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="647.5105"> <colgroup> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> <col width="14.2857142857143%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="justify" class="Lrule Rrule" valign="middle"><span class="Bold">Dose (mg) </span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">N </span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">LDL-C </span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">HDL-C </span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">Total-C </span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">TG</span><span class="Italics"><span class="Sup">1</span></span></td><td align="justify" class="Rrule" valign="middle"><span class="Bold">ApoB </span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Placebo</td><td align="justify" class="Rrule" valign="middle">46</td><td align="justify" class="Rrule" valign="middle">-1%</td><td align="justify" class="Rrule" valign="middle">+7%</td><td align="justify" class="Rrule" valign="middle">0%</td><td align="justify" class="Rrule" valign="middle">-7%</td><td align="justify" class="Rrule" valign="middle">-2%</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">5</td><td align="justify" class="Rrule" valign="middle">42</td><td align="justify" class="Rrule" valign="middle">-38%</td><td align="justify" class="Rrule" valign="middle">+4%<span class="Italics"><span class="Sup">2 </span></span></td><td align="justify" class="Rrule" valign="middle">-30%</td><td align="justify" class="Rrule" valign="middle">-13%<span class="Italics"><span class="Sup">2</span></span></td><td align="justify" class="Rrule" valign="middle">-32%</td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">10</td><td align="justify" class="Rrule" valign="middle">44</td><td align="justify" class="Rrule" valign="middle">-45%</td><td align="justify" class="Rrule" valign="middle">+11%<span class="Italics"><span class="Sup">2</span></span></td><td align="justify" class="Rrule" valign="middle">-34%</td><td align="justify" class="Rrule" valign="middle">-15%<span class="Italics"><span class="Sup">2 </span></span></td><td align="justify" class="Rrule" valign="middle">-38%</td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="middle">20</td><td align="justify" class="Rrule" valign="middle">44</td><td align="justify" class="Rrule" valign="middle">-50%</td><td align="justify" class="Rrule" valign="middle">+9%<span class="Italics"><span class="Sup">2</span></span></td><td align="justify" class="Rrule" valign="middle">-39%</td><td align="justify" class="Rrule" valign="middle">16%<span class="Italics"><span class="Sup">2</span></span></td><td align="justify" class="Rrule" valign="middle">-41%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"647.5105\">\n<colgroup>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n<col width=\"14.2857142857143%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\"><span class=\"Bold\">Dose (mg) </span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">N </span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">LDL-C </span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">HDL-C </span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">Total-C </span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">TG</span><span class=\"Italics\"><span class=\"Sup\">1</span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">ApoB </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\">Placebo</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">46</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-1%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">+7%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">0%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-7%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-2%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\">5</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">42</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-38%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">+4%<span class=\"Italics\"><span class=\"Sup\">2 </span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-30%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-13%<span class=\"Italics\"><span class=\"Sup\">2</span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-32%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\">10</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">44</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-45%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">+11%<span class=\"Italics\"><span class=\"Sup\">2</span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-34%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-15%<span class=\"Italics\"><span class=\"Sup\">2 </span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-38%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"middle\">20</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">44</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-50%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">+9%<span class=\"Italics\"><span class=\"Sup\">2</span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-39%</td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">16%<span class=\"Italics\"><span class=\"Sup\">2</span></span></td><td align=\"justify\" class=\"Rrule\" valign=\"middle\">-41%</td>\n</tr>\n</tbody>\n</table></div>" }

1 Median percent change

{ "type": "p", "children": [], "text": "\n1 Median percent change" }

2 Difference from placebo not statistically significant

{ "type": "p", "children": [], "text": "\n2 Difference from placebo not statistically significant" }

Rosuvastatin was also studied in a two year open-label, uncontrolled, titration-to-goal trial that included 175 pediatric patients with HeFH who were 8 to 17 years old (79 males and 96 females). All patients had a documented genetic defect in the LDL receptor or in ApoB. Approximately 89% were White, 7% were Asian, 1% were Black or African American, and fewer than 1% were Hispanic or Latino ethnicity. Mean LDL-C at baseline was 236 mg/dL. Fifty-eight (33%) patients were prepubertal at baseline. The starting rosuvastatin dosage for all pediatric patients was 5 mg once daily.  Pediatric patients aged 8 to less than 10 years (n=41 at baseline) could titrate to a maximum dosage of 10 mg once daily, and pediatric patients aged 10 to 17 years could titrate to a maximum dosage of 20 mg once daily.

{ "type": "p", "children": [], "text": "Rosuvastatin was also studied in a two year open-label, uncontrolled, titration-to-goal trial that included 175 pediatric patients with HeFH who were 8 to 17 years old (79 males and 96 females). All patients had a documented genetic defect in the LDL receptor or in ApoB. Approximately 89% were White, 7% were Asian, 1% were Black or African American, and fewer than 1% were Hispanic or Latino ethnicity. Mean LDL-C at baseline was 236 mg/dL. Fifty-eight (33%) patients were prepubertal at baseline. The starting rosuvastatin dosage for all pediatric patients was 5 mg once daily.  Pediatric patients aged 8 to less than 10 years (n=41 at baseline) could titrate to a maximum dosage of 10 mg once daily, and pediatric patients aged 10 to 17 years could titrate to a maximum dosage of 20 mg once daily." }

The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous experience in both adult and pediatric controlled trials.

{ "type": "p", "children": [], "text": "The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous experience in both adult and pediatric controlled trials." }

HoFH in Adult and Pediatric Patients

{ "type": "p", "children": [], "text": "\n HoFH in Adult and Pediatric Patients\n" }

In an open-label, forced-titration study, HoFH patients (n=40, 8 to 63 years) were evaluated for their response to rosuvastatin 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-C 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.

{ "type": "p", "children": [], "text": "In an open-label, forced-titration study, HoFH patients (n=40, 8 to 63 years) were evaluated for their response to rosuvastatin 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-C 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." }

HoFH in Pediatric Patients

{ "type": "p", "children": [], "text": "\n HoFH in Pediatric Patients\n" }

Rosuvastatin was studied in a randomized, double-blind, placebo-controlled, multicenter, cross-over study in 14 pediatric patients with HoFH. The study included a 4-week dietary lead-in phase during which patients received rosuvastatin 10 mg daily, a cross-over phase that included two 6-week treatment periods with either rosuvastatin 20 mg or placebo in random order, followed by a 12-week open-label phase during which all patients received rosuvastatin 20 mg. Patients ranged in age from 7 to 15 years of age (median 11 years), 50% were male, 71% were White, 21% were Asian, 7% were Black or African American, and no patients were of Hispanic or Latino ethnicity. Fifty percent were on apheresis therapy and 57% were taking ezetimibe. Patients who entered the study on apheresis therapy or ezetimibe continued the treatment throughout the entire study. Mean LDL-C at baseline was 416 mg/dL (range 152 to 716 mg/dL). A total of 13 patients completed both treatment periods of the randomized crossover phase; one patient withdrew consent due to inability to have blood drawn during the cross-over phase.

{ "type": "p", "children": [], "text": "Rosuvastatin was studied in a randomized, double-blind, placebo-controlled, multicenter, cross-over study in 14 pediatric patients with HoFH. The study included a 4-week dietary lead-in phase during which patients received rosuvastatin 10 mg daily, a cross-over phase that included two 6-week treatment periods with either rosuvastatin 20 mg or placebo in random order, followed by a 12-week open-label phase during which all patients received rosuvastatin 20 mg. Patients ranged in age from 7 to 15 years of age (median 11 years), 50% were male, 71% were White, 21% were Asian, 7% were Black or African American, and no patients were of Hispanic or Latino ethnicity. Fifty percent were on apheresis therapy and 57% were taking ezetimibe. Patients who entered the study on apheresis therapy or ezetimibe continued the treatment throughout the entire study. Mean LDL-C at baseline was 416 mg/dL (range 152 to 716 mg/dL). A total of 13 patients completed both treatment periods of the randomized crossover phase; one patient withdrew consent due to inability to have blood drawn during the cross-over phase." }

Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo (see Table 14).

{ "type": "p", "children": [], "text": "Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo (see Table 14)." }

Table 14: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 7 to 15 years of Age with HoFH After 6 Weeks

{ "type": "p", "children": [], "text": "\nTable 14: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 7 to 15 years of Age with HoFH After 6 Weeks\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="663.803"> <colgroup> <col width="24.9949909837708%"/> <col width="24.9949909837708%"/> <col width="25.0050090162292%"/> <col width="25.0050090162292%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td align="center" class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"><span class="Bold">Placebo </span> <br/> <span class="Bold">(N=13)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Rosuvastatin </span><span class="Bold">20 mg (N=13)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Percent difference (95% CI)</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">LDL-C (mg/dL)</td><td align="center" class="Rrule" valign="top">481</td><td align="center" class="Rrule" valign="top">396</td><td align="justify" class="Rrule" valign="top">-22.3% (-33.5, -9.1)<span class="Sup">1 </span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Total-C (mg/dL)</td><td align="center" class="Rrule" valign="top">539</td><td align="center" class="Rrule" valign="top">448</td><td align="justify" class="Rrule" valign="top">-20.1% (-29.7, -9.1)<span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top">Non-HDL-C (mg/dL)</td><td align="center" class="Rrule" valign="top">505</td><td align="center" class="Rrule" valign="top">412</td><td align="justify" class="Rrule" valign="top">-22.9% (-33.7, -10.3)<span class="Sup">2 </span></td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">ApoB (mg/dL)</td><td align="center" class="Rrule" valign="top">268</td><td align="center" class="Rrule" valign="top">235</td><td align="justify" class="Rrule" valign="top">-17.1% (-29.2, -2.9)<span class="Sup">3</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"663.803\">\n<colgroup>\n<col width=\"24.9949909837708%\"/>\n<col width=\"24.9949909837708%\"/>\n<col width=\"25.0050090162292%\"/>\n<col width=\"25.0050090162292%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Placebo </span>\n<br/>\n<span class=\"Bold\">(N=13)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin </span><span class=\"Bold\">20 mg (N=13)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Percent difference (95% CI)</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">LDL-C (mg/dL)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">481</td><td align=\"center\" class=\"Rrule\" valign=\"top\">396</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-22.3% (-33.5, -9.1)<span class=\"Sup\">1 </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Total-C (mg/dL)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">539</td><td align=\"center\" class=\"Rrule\" valign=\"top\">448</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-20.1% (-29.7, -9.1)<span class=\"Sup\">2</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">Non-HDL-C (mg/dL)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">505</td><td align=\"center\" class=\"Rrule\" valign=\"top\">412</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-22.9% (-33.7, -10.3)<span class=\"Sup\">2 </span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">ApoB (mg/dL)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">268</td><td align=\"center\" class=\"Rrule\" valign=\"top\">235</td><td align=\"justify\" class=\"Rrule\" valign=\"top\">-17.1% (-29.2, -2.9)<span class=\"Sup\">3</span></td>\n</tr>\n</tbody>\n</table></div>" }

% Difference estimates are based on transformations of the estimated mean difference in log LDL measurements between rosuvastatin and placebo using a mixed model adjusted for study period

{ "type": "p", "children": [], "text": "% Difference estimates are based on transformations of the estimated mean difference in log LDL measurements between rosuvastatin and placebo using a mixed model adjusted for study period" }

1 p=0.005, 2 p=0.003, 3 p=0.024

{ "type": "p", "children": [], "text": "\n1 p=0.005, 2 p=0.003, 3 p=0.024" }

Primary Dysbetalipoproteinemia in Adults

{ "type": "p", "children": [], "text": "\n Primary Dysbetalipoproteinemia in Adults\n" }

In a randomized, multicenter, double-blind cross-over study, 32 adult patients (27 with є2/є2 and 4 with apo E mutation [Arg145Cys] with primary dysbetalipoproteinemia entered a 6-week dietary lead-in period on the NCEP Therapeutic Lifestyle Change (TLC) diet.

{ "type": "p", "children": [], "text": "In a randomized, multicenter, double-blind cross-over study, 32 adult patients (27 with є2/є2 and 4 with apo E mutation [Arg145Cys] with primary dysbetalipoproteinemia 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 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.

{ "type": "p", "children": [], "text": "Following dietary lead-in, patients were randomized to a sequence of treatments 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 15: Lipid-Modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32)

{ "type": "p", "children": [], "text": "\nTable 15: Lipid-Modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32)\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="635.74"> <colgroup> <col width="21.8410041841004%"/> <col width="21.9874476987448%"/> <col width="28.0857740585774%"/> <col width="28.0857740585774%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"><span class="Bold">Median at Baseline (mg/dL)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Median percent change from baseline</span> <br/> <span class="Bold">(95% CI)</span> <br/> <span class="Bold">Rosuvastatin 10 mg</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Median percent change from baseline</span> <br/> <span class="Bold">(95% CI)</span> <br/> <span class="Bold">Rosuvastatin 20 mg</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Total-C</td><td align="center" class="Rrule" valign="top">342.5</td><td align="center" class="Rrule" valign="top">-43.3 (-46.9, -37.5)</td><td align="center" class="Rrule" valign="top">-47.6 (-51.6,-42.8)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Triglycerides</td><td align="center" class="Rrule" valign="top">503.5</td><td align="center" class="Rrule" valign="top">-40.1 (-44.9, -33.6)</td><td align="center" class="Rrule" valign="top">-43 (-52.5, -33.1)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Non-HDL-C</td><td align="center" class="Rrule" valign="top">294.5</td><td align="center" class="Rrule" valign="top">-48.2 (-56.7, -45.6)</td><td align="center" class="Rrule" valign="top">-56.4 (-61.4, -48.5)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">VLDL-C + IDL-C</td><td align="center" class="Rrule" valign="top">209.5</td><td align="center" class="Rrule" valign="top">-46.8 (-53.7, -39.4)</td><td align="center" class="Rrule" valign="top">-56.2 (-67.7, -43.7)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">LDL-C</td><td align="center" class="Rrule" valign="top">112.5</td><td align="center" class="Rrule" valign="top">-54.4 (-59.1, -47.3)</td><td align="center" class="Rrule" valign="top">-57.3 (-59.4, -52.1)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">HDL-C</td><td align="center" class="Rrule" valign="top">35.5</td><td align="center" class="Rrule" valign="top">10.2 (1.9, 12.3)</td><td align="center" class="Rrule" valign="top">11.2 (8.3, 20.5)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">RLP-C</td><td align="center" class="Rrule" valign="top">82</td><td align="center" class="Rrule" valign="top">-56.4 (-67.1, -49)</td><td align="center" class="Rrule" valign="top">-64.9 (-74, -56.6)</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Apo-E</td><td align="center" class="Rrule" valign="top">16</td><td align="center" class="Rrule" valign="top">-42.9 (-46.3, -33.3)</td><td align="center" class="Rrule" valign="top">-42.5 (-47.1, -35.6)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"635.74\">\n<colgroup>\n<col width=\"21.8410041841004%\"/>\n<col width=\"21.9874476987448%\"/>\n<col width=\"28.0857740585774%\"/>\n<col width=\"28.0857740585774%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td class=\"Lrule Rrule\" valign=\"top\"></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Median at Baseline (mg/dL)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Median percent change from baseline</span>\n<br/>\n<span class=\"Bold\">(95% CI)</span>\n<br/>\n<span class=\"Bold\">Rosuvastatin 10 mg</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Median percent change from baseline</span>\n<br/>\n<span class=\"Bold\">(95% CI)</span>\n<br/>\n<span class=\"Bold\">Rosuvastatin 20 mg</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Total-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">342.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43.3 (-46.9, -37.5)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-47.6 (-51.6,-42.8)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Triglycerides</td><td align=\"center\" class=\"Rrule\" valign=\"top\">503.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-40.1 (-44.9, -33.6)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43 (-52.5, -33.1)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Non-HDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">294.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-48.2 (-56.7, -45.6)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-56.4 (-61.4, -48.5)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">VLDL-C + IDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">209.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-46.8 (-53.7, -39.4)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-56.2 (-67.7, -43.7)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">LDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">112.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-54.4 (-59.1, -47.3)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-57.3 (-59.4, -52.1)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">HDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">35.5</td><td align=\"center\" class=\"Rrule\" valign=\"top\">10.2 (1.9, 12.3)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">11.2 (8.3, 20.5)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">RLP-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">82</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-56.4 (-67.1, -49)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-64.9 (-74, -56.6)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" valign=\"top\">Apo-E</td><td align=\"center\" class=\"Rrule\" valign=\"top\">16</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-42.9 (-46.3, -33.3)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-42.5 (-47.1, -35.6)</td>\n</tr>\n</tbody>\n</table></div>" }

Hypertriglyceridemia in Adults

{ "type": "p", "children": [], "text": "\n Hypertriglyceridemia in Adults\n" }

In a double-blind, placebo-controlled study in adult 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 (see Table 16).

{ "type": "p", "children": [], "text": "In a double-blind, placebo-controlled study in adult 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 (see Table 16)." }

Table 16: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Primary Hypertriglyceridemia After Six Weeks by Median (Min, Max) Percent Change from Baseline to Week 6

{ "type": "p", "children": [], "text": "\nTable 16: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Primary Hypertriglyceridemia After Six Weeks by Median (Min, Max) Percent Change from Baseline to Week 6\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="668"> <colgroup> <col width="15.6624102154828%"/> <col width="16.2709497206704%"/> <col width="16.8096568236233%"/> <col width="16.7996807661612%"/> <col width="16.8096568236233%"/> <col width="17.6476456504389%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First"> <td class="Lrule Rrule" valign="top"><span class="Bold">Dose </span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Placebo (n=26)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Rosuvastatin </span> <br/> <span class="Bold">5 mg </span> <br/> <span class="Bold">(n=25)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">10 mg </span> <br/> <span class="Bold">(n=23)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">20 mg </span> <br/> <span class="Bold">(n=27)</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Rosuvastatin</span> <br/> <span class="Bold">40 mg </span> <br/> <span class="Bold">(n=25)</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Triglycerides</td><td align="center" class="Rrule" valign="top">1 (-40, 72)</td><td align="center" class="Rrule" valign="top">-21 (-58, 38)</td><td align="center" class="Rrule" valign="top">-37 (-65, 5)</td><td align="center" class="Rrule" valign="top">-37 (-72, 11)</td><td align="center" class="Rrule" valign="top">-43 (-80, -7)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Non-HDL-C</td><td align="center" class="Rrule" valign="top">2 (-13, 19)</td><td align="center" class="Rrule" valign="top">-29 (-43, -8)</td><td align="center" class="Rrule" valign="top">-49 (-59, -20)</td><td align="center" class="Rrule" valign="top">-43 (-74, 12)</td><td align="center" class="Rrule" valign="top">-51 (-62, -6)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Total-C</td><td align="center" class="Rrule" valign="top">1 (-13, 17)</td><td align="center" class="Rrule" valign="top">-24 (-40, -4)</td><td align="center" class="Rrule" valign="top">-40 (-51, -14)</td><td align="center" class="Rrule" valign="top">-34 (-61, -11)</td><td align="center" class="Rrule" valign="top">-40 (-51, -4)</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">LDL-C</td><td align="center" class="Rrule" valign="top">5 (-30, 52)</td><td align="center" class="Rrule" valign="top">-28 (-71, 2)</td><td align="center" class="Rrule" valign="top">-45 (-59, 7)</td><td align="center" class="Rrule" valign="top">-31 (-66, 34)</td><td align="center" class="Rrule" valign="top">-43 (-61, -3)</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">HDL-C</td><td align="center" class="Rrule" valign="top">-3 (-25, 18)</td><td align="center" class="Rrule" valign="top">3 (-38, 33)</td><td align="center" class="Rrule" valign="top">8 (-8, 24)</td><td align="center" class="Rrule" valign="top">22 (-5, 50)</td><td align="center" class="Rrule" valign="top">17 (-14, 63)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"668\">\n<colgroup>\n<col width=\"15.6624102154828%\"/>\n<col width=\"16.2709497206704%\"/>\n<col width=\"16.8096568236233%\"/>\n<col width=\"16.7996807661612%\"/>\n<col width=\"16.8096568236233%\"/>\n<col width=\"17.6476456504389%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Dose </span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Placebo (n=26)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin </span>\n<br/>\n<span class=\"Bold\">5 mg </span>\n<br/>\n<span class=\"Bold\">(n=25)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin</span>\n<br/>\n<span class=\"Bold\">10 mg </span>\n<br/>\n<span class=\"Bold\">(n=23)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin</span>\n<br/>\n<span class=\"Bold\">20 mg </span>\n<br/>\n<span class=\"Bold\">(n=27)</span></td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Rosuvastatin</span>\n<br/>\n<span class=\"Bold\">40 mg </span>\n<br/>\n<span class=\"Bold\">(n=25)</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Triglycerides</td><td align=\"center\" class=\"Rrule\" valign=\"top\">1 (-40, 72)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-21 (-58, 38)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-37 (-65, 5)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-37 (-72, 11)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43 (-80, -7)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Non-HDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">2 (-13, 19)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-29 (-43, -8)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-49 (-59, -20)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43 (-74, 12)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-51 (-62, -6)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Total-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">1 (-13, 17)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-24 (-40, -4)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-40 (-51, -14)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-34 (-61, -11)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-40 (-51, -4)</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">LDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">5 (-30, 52)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-28 (-71, 2)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-45 (-59, 7)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-31 (-66, 34)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-43 (-61, -3)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" valign=\"top\">HDL-C</td><td align=\"center\" class=\"Rrule\" valign=\"top\">-3 (-25, 18)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">3 (-38, 33)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">8 (-8, 24)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">22 (-5, 50)</td><td align=\"center\" class=\"Rrule\" valign=\"top\">17 (-14, 63)</td>\n</tr>\n</tbody>\n</table></div>" }

EZALLOR SPRINKLE (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:

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE (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 47335-984-83

{ "type": "p", "children": [], "text": "Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-984-83" }

Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-984-81

{ "type": "p", "children": [], "text": "Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-984-81" }

Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-984-64

{ "type": "p", "children": [], "text": "Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-984-64" }

EZALLOR SPRINKLE (rosuvastatin) 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:

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE (rosuvastatin) 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 47335-985-83

{ "type": "p", "children": [], "text": "Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-985-83" }

Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-985-81

{ "type": "p", "children": [], "text": "Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-985-81" }

Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-985-64

{ "type": "p", "children": [], "text": "Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-985-64" }

EZALLOR SPRINKLE (rosuvastatin) 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:

{ "type": "p", "children": [], "text": "\n EZALLOR SPRINKLE (rosuvastatin) 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 47335-986-83

{ "type": "p", "children": [], "text": "Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-986-83" }

Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-986-81

{ "type": "p", "children": [], "text": "Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-986-81" }

Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-986-64

{ "type": "p", "children": [], "text": "Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-986-64" }

EZALLOR SPRINKLE (rosuvastatin) 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:

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE (rosuvastatin) 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 47335-987-83

{ "type": "p", "children": [], "text": "Bottles of 30’s with Child Resistant Closure …………………. NDC 47335-987-83" }

Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-987-81

{ "type": "p", "children": [], "text": "Bottles of 90’s with Child Resistant Closure …………………. NDC 47335-987-81" }

Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-987-64

{ "type": "p", "children": [], "text": "Unit-dose blister pack of 30 (3 × 10) capsules ……………….. NDC 47335-987-64" }

Storage

{ "type": "p", "children": [], "text": "\nStorage\n" }

Store EZALLOR SPRINKLE (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].

{ "type": "p", "children": [], "text": "Store EZALLOR SPRINKLE (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.

{ "type": "p", "children": [], "text": "Protect from moisture." }

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)." }

Myopathy and Rhabdomyolysis

{ "type": "p", "children": [], "text": "\nMyopathy and Rhabdomyolysis\n" }

Advise patients that EZALLOR SPRINKLE may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over-the-counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.1), and Drug Interactions (7.1)].

{ "type": "p", "children": [], "text": "Advise patients that EZALLOR SPRINKLE may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over-the-counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.1), and Drug Interactions (7.1)].\n" }

Hepatic Dysfunction

{ "type": "p", "children": [], "text": "\nHepatic Dysfunction\n" }

Inform patients that EZALLOR SPRINKLE may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that EZALLOR SPRINKLE may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.3)].\n" }

Increases in HbA1c and Fasting Serum Glucose Levels

{ "type": "p", "children": [], "text": "\nIncreases in HbA1c and Fasting Serum Glucose Levels\n" }

Inform patients that increases in HbA1c and fasting serum glucose levels may occur with EZALLOR SPRINKLE. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients that increases in HbA1c and fasting serum glucose levels may occur with EZALLOR SPRINKLE. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions (5.5)].\n" }

Pregnancy

{ "type": "p", "children": [], "text": "\nPregnancy \n" }

Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if EZALLOR SPRINKLE should be discontinued [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if EZALLOR SPRINKLE should be discontinued [see Use in Specific Populations (8.1)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation \n" }

Advise patients that breastfeeding during treatment with EZALLOR SPRINKLE is not recommended [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise patients that breastfeeding during treatment with EZALLOR SPRINKLE is not recommended [see Use in Specific Populations (8.2)]." }

Concomitant Use of Antacids

{ "type": "p", "children": [], "text": "\nConcomitant Use of Antacids\n" }

When taking EZALLOR SPRINKLE with an aluminum and magnesium hydroxide combination antacid, administer EZALLOR SPRINKLE at least 2 hours before the antacid [see Drug Interactions (7.2)].

{ "type": "p", "children": [], "text": "When taking EZALLOR SPRINKLE with an aluminum and magnesium hydroxide combination antacid, administer EZALLOR SPRINKLE at least 2 hours before the antacid [see Drug Interactions (7.2)]." }

Missed Doses

{ "type": "p", "children": [], "text": "\nMissed Doses\n" }

If a dose is missed, advise patients not to take an extra dose. Just resume the usual schedule [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "If a dose is missed, advise patients not to take an extra dose. Just resume the usual schedule [see Dosage and Administration (2.1)]." }

Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512

{ "type": "p", "children": [], "text": "Distributed by:\nSun Pharmaceutical Industries, Inc.\nCranbury, NJ 08512" }

Manufactured by: Sun Pharmaceutical Industries Limited Halol-Baroda Highway,Halol-389 350, Gujarat, India.

{ "type": "p", "children": [], "text": "Manufactured by:\nSun Pharmaceutical Industries Limited\nHalol-Baroda Highway,Halol-389 350, Gujarat, India." }

FDA-05EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited.

{ "type": "p", "children": [], "text": "FDA-05EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited." }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="First"> <td align="center" valign="middle"> <br/> <span class="Bold">EZALLOR  SPRINKLE<span class="Sup">®</span>  [Ez-Aah-Lor Spr-En-Kle] </span> <br/> <span class="Bold">(rosuvastatin) c</span><span class="Bold">apsules, for oral use</span></td> </tr> <tr> <td valign="middle"> Read this Patient Information carefully before you start taking EZALLOR SPRINKLE and each time you get a refill. If you have any questions about EZALLOR SPRINKLE, ask your healthcare provider. Only your healthcare provider can determine if EZALLOR SPRINKLE is right for you.</td> </tr> <tr> <td valign="middle"> <p class="First"> <span class="Bold">What is EZALLOR SPRINKLE?</span> </p> <p>EZALLOR SPRINKLE is a prescription medicine that contains a cholesterol-lowering medicine called rosuvastatin.</p> <ul> <li>EZALLOR SPRINKLE is used:<ul> <li>to reduce the risk of  major adverse cardiovascular (CV) events, such as death from CV disease, heart attack, stroke, or the need for procedures to improve blood flow to the heart called arterial revascularization, in adults who do not have known heart disease but do have certain additional risk factors.</li> </ul> </li> <li>along with diet to:</li> <li>lower the level of low-density lipoprotein (LDL-C) cholesterol or “bad” cholesterol in adults with primary hyperlipidemia.</li> <li>slow the buildup of fatty deposits (plaque) in the walls of blood vessels.</li> <li>treat adults and children 8 years of age and older with high blood cholesterol due to heterozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).<ul> <li>along with other cholesterol lowering treatments or alone if such treatments are unavailable in adults and children 7 years of age and older with homozygous familial hypercholesterolemia (HoFH) (an inherited condition that causes high levels of LDL-C).<ul> <li>   along with diet for the treatment of adults with:</li> <li>primary dysbetalipoproteinemia (an inherited condition that causes high levels of cholesterol and fat).</li> <li>hypertriglyceridemia.</li> </ul> </li> </ul> </li> </ul> <p></p> <p>It is not known if EZALLOR SPRINKLE is safe and effective in children younger than 8 years of age with HeFH or children younger than 7 years of age with HoFH or in children with other types of hyperlipidemias (other than HeFH or HoFH).</p> </td> </tr> <tr> <td valign="middle"> <p class="First"> <span class="Bold">Do not take EZALLOR </span><span class="Bold">SPRINKLE if you:</span> </p> <ul> <li>have liver problems.</li> <li>are allergic to rosuvastatin or any of the ingredients in EZALLOR SPRINKLE. See the end of this leaflet for a complete list of ingredients in EZALLOR SPRINKLE.</li> </ul> </td> </tr> <tr> <td align="justify" valign="middle"> <p class="First"> <span class="Bold">Before you take EZALLOR SPRINKLE, tell your healthcare provider about all of your medical conditions, including if you</span><span class="Bold">:</span> </p> <p></p> <ul> <li>have unexplained muscle aches or weakness.</li> <li>have or have had kidney problems.</li> <li>have or have had liver problems.</li> <li>drink more than 2 glasses of alcohol daily.</li> <li>have thyroid problems.</li> <li>are of Asian descent.</li> </ul> <p></p> <ul> <li>are pregnant or think you may be pregnant, or are planning to become pregnant. If you become pregnant while taking EZALLOR SPRINKLE, call your healthcare provider right away to discuss your EZALLOR SPRINKLE treatment.</li> <li>are breastfeeding. EZALLOR SPRINKLE can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take EZALLOR SPRINKLE. Do not breastfeed while taking EZALLOR SPRINKLE.</li> </ul> <p></p> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider who prescribes EZALLOR SPRINKLE if another healthcare provider increases the dose of another medicine you are taking. EZALLOR SPRINKLE may affect the way other medicines work, and other medicines may affect how EZALLOR SPRINKLE works.</p> <p></p> <p></p> <p></p> <p>Especially tell your healthcare provider if you take:</p> <p></p> <ul> <li>coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)</li> <li>antacids (medicines you take for heartburn that contain aluminum and magnesium hydroxide</li> </ul> <p></p> <p>Taking EZALLOR SPRINKLE with certain medicines may increase the risk of muscle problems.</p> <p></p> <p>Especially tell your healthcare provider if you take:</p> <p></p> <ul> <li>cyclosporine (a medicine for your immune system)</li> <li>teriflunomide (a medicine used to treat relapsing remitting multiple sclerosis)</li> <li>enasidenib (a medicine used to treat acute myeloid leukemia)</li> <li>capmatinib (a medicine for the treatment of non-small cell lung cancer)</li> <li>fostamatinib (a medicine used to treat low platelet counts)</li> <li>febuxostat (a medicine used to treat and prevent high blood levels of uric acid)</li> <li>gemfibrozil (a fibric acid medicine for lowering cholesterol)</li> <li>tafamidis [used to treat cardiomyopathy (enlarged and thickened heart muscle)]</li> <li>anti-viral medicines including certain HIV or hepatitis C virus medicines such as:</li> <li> <ul> <li>lopinavir, ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir</li> <li>combination of</li> <li> <ul> <li>sofosbuvir/velpatasvir/voxilaprevir</li> <li>dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>elbasvir/grazoprevir</li> <li>sofosbuvir/velpatasvir</li> <li>glecaprevir/pibrentasvir <span class="Bold">and</span> </li> </ul> </li> <li>all other combinations with ledipasvir including ledipasvir/sofosbuvir</li> </ul> </li> <li>darolutamide (a medicine for the treatment of prostate cancer)</li> <li>regorafenib (a medicine used to treat cancer of the colon and rectum)</li> <li>fibric acid derivatives (such as fenofibrate)</li> <li>ticagrelor (helps reduce the chance of a blood clot formation that can block a blood vessel)</li> <li>niacin or nicotinic acid</li> <li>colchicine (a medicine used to treat gout)</li> </ul> <p>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get new medicine.</p> </td> </tr> <tr> <td valign="middle"> <p class="First"> <span class="Bold">How should I take EZALLOR SPRINKLE?</span> </p> <ul> <li>Take EZALLOR SPRINKLE exactly as your healthcare provider tells you to take it.</li> <li>Take EZALLOR SPRINKLE, by mouth, 1 time each day, with or without food. Swallow the capsule whole.</li> <li> <span class="Bold">Do not</span> crush or chew EZALLOR SPRINKLE</li> <li>EZALLOR SPRINKLE can be taken at any time of day, with or without food.</li> <li>If you have trouble swallowing a whole capsule, you can open the capsule and take the contents with soft food (applesauce, or chocolate- or vanilla-flavored pudding). <span class="Bold">See the “Instructions for Use”</span> at the end of this Patient Package Information for instructions on how to take EZALLOR SPRINKLE by mouth.</li> <li> <span class="Bold">See the “Instructions for Use”</span> at the end of this Patient Package Information for instructions on how to mix and give EZALLOR SPRINKLE through a nasogastric tube.</li> <li> <span class="Bold">Do not</span> change your dose or stop EZALLOR SPRINKLE without talking to your healthcare provider, even if you are feeling well.</li> <li>Your healthcare provider may do blood tests to check your cholesterol levels before and during your treatment with EZALLOR SPRINKLE. Your healthcare provider may change your dose of EZALLOR SPRINKLE if needed.</li> <li>While taking EZALLOR SPRINKLE, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.</li> <li>If you take a medicine called an antacid that contains a combination of aluminum and magnesium hydroxide, take EZALLOR SPRINKLE at least 2 hours before you take the antacid.</li> <li>If you miss a dose of EZALLOR SPRINKLE, take your next dose at your normal scheduled time. <span class="Bold">Do not take an extra </span>dose of EZALLOR SPRINKLE<span class="Bold">.</span> </li> <li>In case of an overdose, get medical help or contact a live Poison Center expert right away at 1-800-222-1222. Advice is also available online at poisonhelp.org.</li> </ul> </td> </tr> <tr> <td align="justify" valign="middle"> <p class="First"> <span class="Bold">What are the possible side effects of EZALLOR SPRINKLE?</span> </p> <p> <span class="Bold">EZALLOR SPRINKLE may cause serious side effects, including:</span> </p> <ul> <li> <span class="Bold">Muscle pain, tenderness and weakness (myopathy). </span>Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death. Tell your healthcare provider right away if:<ul> <li>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.</li> <li>you have muscle problems that do not go away even after your healthcare provider has told you to stop taking EZALLOR SPRINKLE. Your healthcare provider may do further tests to diagnose the cause of your muscle problems.</li> </ul> </li> </ul> <p>Your chances of getting muscle problems are higher if you:</p> <ul> <li>are taking certain other medicines while you take EZALLOR SPRINKLE (see “Especially tell your healthcare provider if you take”)</li> <li>are 65 years of age or older</li> <li>are of Asian descent</li> <li>have thyroid problems (hypothyroidism) that are not controlled</li> <li>have kidney problems</li> <li>are taking higher doses of EZALLOR SPRINKLE</li> <li> <span class="Bold">Liver problems. </span>Your healthcare provider may 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 healthcare provider right away if you have any of the following symptoms of liver problems:<ul> <li>feel unusually tired or weak</li> <li>loss of appetite</li> <li>upper belly pain</li> <li>dark urine</li> <li>yellowing of your skin or the whites of your eyes</li> </ul> </li> <li> <span class="Bold">Pr</span><span class="Bold">otein and blood in the urine. </span>EZALLOR SPRINKLE may cause you to have protein and blood in your urine. If you develop protein or blood in your urine, your healthcare provider may decrease your dose of EZALLOR SPRINKLE.</li> <li> <span class="Bold">I</span><span class="Bold">ncrease in blood sugar (glucose) levels</span>. EZALLOR SPRINKLE may cause an increase in your blood sugar levels.</li> </ul> <p>The most common side effects may include headache, nausea, muscle aches and pains,  weakness, and constipation.</p> <p class="TableParagraph">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p class="TableParagraph">For more information, ask your healthcare provider or pharmacist.</p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td align="justify" valign="middle"> <p class="First"> <span class="Bold">How should I store EZALLOR SPRINKLE?</span> </p> <ul> <li>Store EZALLOR SPRINKLE at room temperature between 68ºF to 77ºF (20ºC to 25ºC).</li> <li>Store in a dry place.</li> </ul> <p> <span class="Bold">Keep EZALLOR SPRINKLE and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td align="justify" valign="middle"><span class="Bold">General Information about the safe and effective use of EZALLOR SPRINKLE.</span> <br/>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 medical condition you have. It may harm them. <br/> <br/>You can ask your pharmacist or healthcare provider for information about EZALLOR SPRINKLE that is written for health professionals.</td> </tr> <tr class="Last"> <td align="justify" valign="middle"> <br/> <span class="Bold">What are the Ingredients in EZALLOR SPRINKLE?</span> <br/> <span class="Bold">Active Ingredient:</span> rosuvastatin as rosuvastatin calcium<br/> <span class="Bold">Inactive Ingredients:</span> crospovidone, ferric oxide, hypromellose, magnesium oxide, mannitol, microcrystalline cellulose, polyethylene glycol 4000, silicon dioxide, and sodium citrate.<br/> <span class="Bold">Capsule shell:</span> gelatin, sodium lauryl sulfate, titanium dioxide, water and the following colorants: FD &amp; C Red 40 (5 mg), FD &amp; C Blue 1 (5 mg, 10 mg, 20 mg), D &amp; C Red 28 (5 mg, 10 mg), FD &amp; C Red 3 (20 mg), and FD &amp; C Green 3 (40 mg).The imprinting black ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide propylene glycol, purified water, shellac and strong ammonia solution.<br/> <br/>Distributed by:<br/> <span class="Bold">Sun Pharmaceutical Industries, Inc.</span> <br/>Cranbury, NJ 08512<br/> <br/>Manufactured by:<br/> <span class="Bold">Sun Pharmaceutical Industries Limited,</span> <br/>Halol-Baroda Highway, Halol-389 350, Gujarat, India.<br/> <br/>EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited.<br/> <br/>For more information, call 1- 1-800-818-4555.     <br/> <br/>FDA-05<br/> <br/>This Patient Information has been approved by the U.S. Food and Drug Administration<br/> <br/>Issued: 02/2025</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" valign=\"middle\">\n<br/>\n<span class=\"Bold\">EZALLOR  SPRINKLE<span class=\"Sup\">®</span>  [Ez-Aah-Lor Spr-En-Kle] </span>\n<br/>\n<span class=\"Bold\">(rosuvastatin) c</span><span class=\"Bold\">apsules, for oral use</span></td>\n</tr>\n<tr>\n<td valign=\"middle\"> Read this Patient Information carefully before you start taking EZALLOR SPRINKLE and each time you get a refill. If you have any questions about EZALLOR SPRINKLE, ask your healthcare provider. Only your healthcare provider can determine if EZALLOR SPRINKLE is right for you.</td>\n</tr>\n<tr>\n<td valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">What is EZALLOR SPRINKLE?</span>\n</p>\n<p>EZALLOR SPRINKLE is a prescription medicine that contains a cholesterol-lowering medicine called rosuvastatin.</p>\n<ul>\n<li>EZALLOR SPRINKLE is used:<ul>\n<li>to reduce the risk of  major adverse cardiovascular (CV) events, such as death from CV disease, heart attack, stroke, or the need for procedures to improve blood flow to the heart called arterial revascularization, in adults who do not have known heart disease but do have certain additional risk factors.</li>\n</ul>\n</li>\n<li>along with diet to:</li>\n<li>lower the level of low-density lipoprotein (LDL-C) cholesterol or “bad” cholesterol in adults with primary hyperlipidemia.</li>\n<li>slow the buildup of fatty deposits (plaque) in the walls of blood vessels.</li>\n<li>treat adults and children 8 years of age and older with high blood cholesterol due to heterozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).<ul>\n<li>along with other cholesterol lowering treatments or alone if such treatments are unavailable in adults and children 7 years of age and older with homozygous familial hypercholesterolemia (HoFH) (an inherited condition that causes high levels of LDL-C).<ul>\n<li>   along with diet for the treatment of adults with:</li>\n<li>primary dysbetalipoproteinemia (an inherited condition that causes high levels of cholesterol and fat).</li>\n<li>hypertriglyceridemia.</li>\n</ul>\n</li>\n</ul>\n</li>\n</ul>\n<p></p>\n<p>It is not known if EZALLOR SPRINKLE is safe and effective in children younger than 8 years of age with HeFH or children younger than 7 years of age with HoFH or in children with other types of hyperlipidemias (other than HeFH or HoFH).</p>\n</td>\n</tr>\n<tr>\n<td valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take EZALLOR </span><span class=\"Bold\">SPRINKLE if you:</span>\n</p>\n<ul>\n<li>have liver problems.</li>\n<li>are allergic to rosuvastatin or any of the ingredients in EZALLOR SPRINKLE. See the end of this leaflet for a complete list of ingredients in EZALLOR SPRINKLE.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"justify\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Before you take EZALLOR SPRINKLE, tell your healthcare provider about all of your medical conditions, including if you</span><span class=\"Bold\">:</span>\n</p>\n<p></p>\n<ul>\n<li>have unexplained muscle aches or weakness.</li>\n<li>have or have had kidney problems.</li>\n<li>have or have had liver problems.</li>\n<li>drink more than 2 glasses of alcohol daily.</li>\n<li>have thyroid problems.</li>\n<li>are of Asian descent.</li>\n</ul>\n<p></p>\n<ul>\n<li>are pregnant or think you may be pregnant, or are planning to become pregnant. If you become pregnant while taking EZALLOR SPRINKLE, call your healthcare provider right away to discuss your EZALLOR SPRINKLE treatment.</li>\n<li>are breastfeeding. EZALLOR SPRINKLE can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take EZALLOR SPRINKLE. Do not breastfeed while taking EZALLOR SPRINKLE.</li>\n</ul>\n<p></p>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider who prescribes EZALLOR SPRINKLE if another healthcare provider increases the dose of another medicine you are taking. EZALLOR SPRINKLE may affect the way other medicines work, and other medicines may affect how EZALLOR SPRINKLE works.</p>\n<p></p>\n<p></p>\n<p></p>\n<p>Especially tell your healthcare provider if you take:</p>\n<p></p>\n<ul>\n<li>coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)</li>\n<li>antacids (medicines you take for heartburn that contain aluminum and magnesium hydroxide</li>\n</ul>\n<p></p>\n<p>Taking EZALLOR SPRINKLE with certain medicines may increase the risk of muscle problems.</p>\n<p></p>\n<p>Especially tell your healthcare provider if you take:</p>\n<p></p>\n<ul>\n<li>cyclosporine (a medicine for your immune system)</li>\n<li>teriflunomide (a medicine used to treat relapsing remitting multiple sclerosis)</li>\n<li>enasidenib (a medicine used to treat acute myeloid leukemia)</li>\n<li>capmatinib (a medicine for the treatment of non-small cell lung cancer)</li>\n<li>fostamatinib (a medicine used to treat low platelet counts)</li>\n<li>febuxostat (a medicine used to treat and prevent high blood levels of uric acid)</li>\n<li>gemfibrozil (a fibric acid medicine for lowering cholesterol)</li>\n<li>tafamidis [used to treat cardiomyopathy (enlarged and thickened heart muscle)]</li>\n<li>anti-viral medicines including certain HIV or hepatitis C virus medicines such as:</li>\n<li>\n<ul>\n<li>lopinavir, ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir</li>\n<li>combination of</li>\n<li>\n<ul>\n<li>sofosbuvir/velpatasvir/voxilaprevir</li>\n<li>dasabuvir/ombitasvir/paritaprevir/ritonavir</li>\n<li>elbasvir/grazoprevir</li>\n<li>sofosbuvir/velpatasvir</li>\n<li>glecaprevir/pibrentasvir <span class=\"Bold\">and</span>\n</li>\n</ul>\n</li>\n<li>all other combinations with ledipasvir including ledipasvir/sofosbuvir</li>\n</ul>\n</li>\n<li>darolutamide (a medicine for the treatment of prostate cancer)</li>\n<li>regorafenib (a medicine used to treat cancer of the colon and rectum)</li>\n<li>fibric acid derivatives (such as fenofibrate)</li>\n<li>ticagrelor (helps reduce the chance of a blood clot formation that can block a blood vessel)</li>\n<li>niacin or nicotinic acid</li>\n<li>colchicine (a medicine used to treat gout)</li>\n</ul>\n<p>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get new medicine.</p>\n</td>\n</tr>\n<tr>\n<td valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take EZALLOR SPRINKLE?</span>\n</p>\n<ul>\n<li>Take EZALLOR SPRINKLE exactly as your healthcare provider tells you to take it.</li>\n<li>Take EZALLOR SPRINKLE, by mouth, 1 time each day, with or without food. Swallow the capsule whole.</li>\n<li>\n<span class=\"Bold\">Do not</span> crush or chew EZALLOR SPRINKLE</li>\n<li>EZALLOR SPRINKLE can be taken at any time of day, with or without food.</li>\n<li>If you have trouble swallowing a whole capsule, you can open the capsule and take the contents with soft food (applesauce, or chocolate- or vanilla-flavored pudding). <span class=\"Bold\">See the “Instructions for Use”</span> at the end of this Patient Package Information for instructions on how to take EZALLOR SPRINKLE by mouth.</li>\n<li>\n<span class=\"Bold\">See the “Instructions for Use”</span> at the end of this Patient Package Information for instructions on how to mix and give EZALLOR SPRINKLE through a nasogastric tube.</li>\n<li>\n<span class=\"Bold\">Do not</span> change your dose or stop EZALLOR SPRINKLE without talking to your healthcare provider, even if you are feeling well.</li>\n<li>Your healthcare provider may do blood tests to check your cholesterol levels before and during your treatment with EZALLOR SPRINKLE. Your healthcare provider may change your dose of EZALLOR SPRINKLE if needed.</li>\n<li>While taking EZALLOR SPRINKLE, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.</li>\n<li>If you take a medicine called an antacid that contains a combination of aluminum and magnesium hydroxide, take EZALLOR SPRINKLE at least 2 hours before you take the antacid.</li>\n<li>If you miss a dose of EZALLOR SPRINKLE, take your next dose at your normal scheduled time. <span class=\"Bold\">Do not take an extra </span>dose of EZALLOR SPRINKLE<span class=\"Bold\">.</span>\n</li>\n<li>In case of an overdose, get medical help or contact a live Poison Center expert right away at 1-800-222-1222. Advice is also available online at poisonhelp.org.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"justify\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of EZALLOR SPRINKLE?</span>\n</p>\n<p>\n<span class=\"Bold\">EZALLOR SPRINKLE may cause serious side effects, including:</span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">Muscle pain, tenderness and weakness (myopathy). </span>Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death. Tell your healthcare provider right away if:<ul>\n<li>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.</li>\n<li>you have muscle problems that do not go away even after your healthcare provider has told you to stop taking EZALLOR SPRINKLE. Your healthcare provider may do further tests to diagnose the cause of your muscle problems.</li>\n</ul>\n</li>\n</ul>\n<p>Your chances of getting muscle problems are higher if you:</p>\n<ul>\n<li>are taking certain other medicines while you take EZALLOR SPRINKLE (see “Especially tell your healthcare provider if you take”)</li>\n<li>are 65 years of age or older</li>\n<li>are of Asian descent</li>\n<li>have thyroid problems (hypothyroidism) that are not controlled</li>\n<li>have kidney problems</li>\n<li>are taking higher doses of EZALLOR SPRINKLE</li>\n<li>\n<span class=\"Bold\">Liver problems. </span>Your healthcare provider may 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 healthcare provider right away if you have any of the following symptoms of liver problems:<ul>\n<li>feel unusually tired or weak</li>\n<li>loss of appetite</li>\n<li>upper belly pain</li>\n<li>dark urine</li>\n<li>yellowing of your skin or the whites of your eyes</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Pr</span><span class=\"Bold\">otein and blood in the urine. </span>EZALLOR SPRINKLE may cause you to have protein and blood in your urine. If you develop protein or blood in your urine, your healthcare provider may decrease your dose of EZALLOR SPRINKLE.</li>\n<li>\n<span class=\"Bold\">I</span><span class=\"Bold\">ncrease in blood sugar (glucose) levels</span>. EZALLOR SPRINKLE may cause an increase in your blood sugar levels.</li>\n</ul>\n<p>The most common side effects may include headache, nausea, muscle aches and pains,  weakness, and constipation.</p>\n<p class=\"TableParagraph\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p class=\"TableParagraph\">For more information, ask your healthcare provider or pharmacist.</p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td align=\"justify\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store EZALLOR SPRINKLE?</span>\n</p>\n<ul>\n<li>Store EZALLOR SPRINKLE at room temperature between 68ºF to 77ºF (20ºC to 25ºC).</li>\n<li>Store in a dry place.</li>\n</ul>\n<p>\n<span class=\"Bold\">Keep EZALLOR SPRINKLE and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"justify\" valign=\"middle\"><span class=\"Bold\">General Information about the safe and effective use of EZALLOR SPRINKLE.</span>\n<br/>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 medical condition you have. It may harm them. <br/>\n<br/>You can ask your pharmacist or healthcare provider for information about EZALLOR SPRINKLE that is written for health professionals.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" valign=\"middle\">\n<br/>\n<span class=\"Bold\">What are the Ingredients in EZALLOR SPRINKLE?</span>\n<br/>\n<span class=\"Bold\">Active Ingredient:</span> rosuvastatin as rosuvastatin calcium<br/>\n<span class=\"Bold\">Inactive Ingredients:</span> crospovidone, ferric oxide, hypromellose, magnesium oxide, mannitol, microcrystalline cellulose, polyethylene glycol 4000, silicon dioxide, and sodium citrate.<br/>\n<span class=\"Bold\">Capsule shell:</span> gelatin, sodium lauryl sulfate, titanium dioxide, water and the following colorants: FD &amp; C Red 40 (5 mg), FD &amp; C Blue 1 (5 mg, 10 mg, 20 mg), D &amp; C Red 28 (5 mg, 10 mg), FD &amp; C Red 3 (20 mg), and FD &amp; C Green 3 (40 mg).The imprinting black ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide propylene glycol, purified water, shellac and strong ammonia solution.<br/>\n<br/>Distributed by:<br/>\n<span class=\"Bold\">Sun Pharmaceutical Industries, Inc.</span>\n<br/>Cranbury, NJ 08512<br/>\n<br/>Manufactured by:<br/>\n<span class=\"Bold\">Sun Pharmaceutical Industries Limited,</span>\n<br/>Halol-Baroda Highway, Halol-389 350, Gujarat, India.<br/>\n<br/>EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited.<br/>\n<br/>For more information, call 1- 1-800-818-4555.     <br/>\n<br/>FDA-05<br/>\n<br/>This Patient Information has been approved by the U.S. Food and Drug Administration<br/>\n<br/>Issued: 02/2025</td>\n</tr>\n</tbody>\n</table></div>" }

EZALLOR SPRINKLE® [Ez-Aah-Lor Spr-En-Kle]

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(rosuvastatin) capsules, for oral use

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Taking EZALLOR SPRINKLE with soft food (applesauce, or chocolate- or vanilla-flavored pudding):

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For people who have difficulty in swallowing capsules, EZALLOR SPRINKLE may be given with soft food (applesauce, or chocolate- or vanilla-flavored pudding) as follows:

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Giving EZALLOR SPRINKLE through a nasogastric tube (NG tube) 16 French or larger, as prescribed by your doctor:

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For people who have a nasogastric tube in place, EZALLOR SPRINKLE may be given as follows:

{ "type": "p", "children": [], "text": "For people who have a nasogastric tube in place, EZALLOR SPRINKLE may be given as follows:" }

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How should I store EZALLOR SPRINKLE?

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Keep EZALLOR SPRINKLE and all medicines out of the reach of children.

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This Instructions for Use has been approved by the U.S. Food and Drug Administration.

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Distributed by:

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Sun Pharmaceutical Industries, Inc.

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Cranbury, NJ 08512

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Manufactured by:

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Sun Pharmaceutical Industries Limited,.

{ "type": "p", "children": [], "text": "\nSun Pharmaceutical Industries Limited,. \n" }

Halol-Baroda Highway,

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Halol-389 350, Gujarat, India.

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Version: 02/2025

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FDA-04

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EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited.

{ "type": "p", "children": [], "text": "EZALLOR SPRINKLE is a registered trademark of Sun Pharmaceutical Industries Limited." }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

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NDC 47335-984-64

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Ezallor SprinkleTM (rosuvastatin) Capsules

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5 mg

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PHARMACIST: Please dispense with Patient Information provided separately to each patient.

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Rx only

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30 (3 × 10) Unit-Dose Capsules

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NDC 47335-985-83

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Ezallor SprinkleTM (rosuvastatin) Capsules

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10 mg

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PHARMACIST: Please dispense with Patient Information provided separately to each patient.

{ "type": "p", "children": [], "text": "\nPHARMACIST: Please dispense with Patient Information provided separately to each patient.\n" }

Rx only

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30 Capsules

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NDC 47335-985-64

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EzallorSprinkleTM (rosuvastatin) Capsules

{ "type": "p", "children": [], "text": "\nEzallorSprinkleTM\n\n(rosuvastatin) Capsules\n" }

10 mg

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PHARMACIST: Please dispense with Patient Information provided separately to each patient.

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Rx only

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30 (3 × 10) Unit-Dose Capsules

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Rosuvastatin tablets are indicated:

{ "type": "p", "children": [], "text": "Rosuvastatin tablets are indicated:" }

{ "type": "ul", "children": [ "\nTo reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor.\n", "As an adjunct to diet to:\n \n \nReduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia.\nReduce LDL-C and slow the progression of atherosclerosis in adults.\nReduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).\n\n" ], "text": "" }

{ "type": "ul", "children": [ "As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH).", "As an adjunct to diet for the treatment of adults with:\n \n \nPrimary dysbetalipoproteinemia.\nHypertriglyceridemia.\n\n" ], "text": "" }

Dosage in Pediatric Patients 8 Years of Age and Older with HeFH

The recommended dosage range is 5 mg to 10 mg orally once daily in patients aged 8 years to less than 10 years and 5 mg to 20 mg orally once daily in patients aged 10 years and older.

Dosage in Pediatric Patients 7 Years of Age and Older with HoFH

The recommended dosage is 20 mg orally once daily.

Initiate rosuvastatin tablets at 5 mg once daily due to increased rosuvastatin plasma concentrations. Consider the risks and benefits of rosuvastatin tablets when treating Asian patients not adequately controlled at doses up to 20 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.3)].

In patients with severe renal impairment (CL crless than 30 mL/min/1.73 m 2) not on hemodialysis, the recommended starting dosage is 5 mg once daily and should not exceed 10 mg once daily [see Warnings and Precautions (5.1)and Use in Specific Populations (8.6)] .

There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.

Table 1 displays dosage modifications for rosuvastatin tablets due to drug interactions [see Warnings and Precautions (5.1)and Drug Interactions (7.1)].

<div class="scrollingtable"><table width="70%"> <caption> <span>Table 1: Rosuvastatin tablets Dosage Modifications Due to Drug Interactions</span> </caption> <col width="50%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Lrule Rrule Toprule" valign="middle"><span class="Bold">Concomitantly Used Drug</span></td><td align="left" class="Rrule Toprule" valign="middle"><span class="Bold">Rosuvastatin tablets Dosage Modifications</span></td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Cyclosporine</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 5 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Teriflunomide</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 10 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Enasidenib</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 10 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Capmatinib</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 10 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Fostamatinib</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 20 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Febuxostat</td><td align="left" class="Rrule Toprule" valign="middle">Do not exceed 20 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Gemfibrozil</td><td align="left" class="Rrule Toprule" valign="middle">Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Tafamidis</td><td align="left" class="Rrule Toprule" valign="middle">Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 20 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" colspan="2" valign="middle">Antiviral Medications</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle"> <ul class="Circle"> <li>Sofbuvir/velpatasvir/voxilaprevir</li> <li>Ledipasvir/sofosbuvir</li> </ul> </td><td align="left" class="Rrule Toprule" valign="top">Concomitant use not recommended.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle"> <ul class="Circle"> <li>Simeprevir</li> <li>Dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>Elbasvir/Grazoprevir</li> <li>Sofosbuvir/Velpatasvir</li> <li>Glecaprevir/Pibrentasvir</li> <li>Atazanavir/Ritonavir</li> <li>Lopinavir/Ritonavir</li> </ul> </td><td align="left" class="Rrule Toprule" valign="top">Initiate at 5 mg once daily. Do not exceed 10 mg once daily.</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="middle">Darolutamide</td><td align="left" class="Rrule Toprule" valign="top">Do not exceed 5 mg once daily.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule Toprule" valign="middle">Regorafenib</td><td align="left" class="Rrule Toprule" valign="top">Do not exceed 10 mg once daily.</td> </tr> </tbody> </table></div>

Rosuvastatin tablets, USP:

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{ "type": "ul", "children": [ "20 mg of rosuvastatin: pink colored, round, biconvex, film coated tablets, debossed with SG on one side and 118 other side." ], "text": "" }

Rosuvastatin tablets are contraindicated in the following conditions:

{ "type": "p", "children": [], "text": "Rosuvastatin tablets are contraindicated in the following conditions:" }

{ "type": "ul", "children": [ "Acute liver failure or decompensated cirrhosis\n \n [see\n \n Warnings and Precautions (5.3)]\n \n .\n \n ", "Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin tablets\n \n [see\n \n Adverse Reactions (6.1)]\n \n .\n \n " ], "text": "" }

Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin.

Risk Factors for Myopathy

Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher rosuvastatin dosage. Asian patients on rosuvastatin may be at higher risk for myopathy [see Drug Interactions (7.1)and Use in Specific Populations (8.8)] . The myopathy risk is greater in patients taking rosuvastatin 40 mg daily compared with lower rosuvastatin dosages.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis

The concomitant use of rosuvastatin with cyclosporine or gemfibrozil is not recommended. Rosuvastatin dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [see Dosage and Administration (2.6)] . Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions (7.1)] .

Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin is discontinued. Temporarily discontinue rosuvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the rosuvastatin dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue rosuvastatin if IMNM is suspected.

Increases in serum transaminases have been reported with use of rosuvastatin [see Adverse Reactions (6.1)] . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to more than three times the ULN occurred in 1.1% of patients taking rosuvastatin versus 0.5% of patients treated with placebo. Marked persistent increases of hepatic transaminases have also occurred with rosuvastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin.

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)] .

Consider liver enzyme testing before rosuvastatin initiation and when clinically indicated thereafter. Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)] . If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue rosuvastatin.

In the rosuvastatin tablets 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 statins, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, consider a dose reduction for patients on rosuvastatin therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.

Increases in HbA1c and fasting serum glucose levels have been reported with statins, 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)] . Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 2. These studies had a treatment duration of up to 12 weeks.

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 2: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and &gt; Placebo in Placebo-Controlled Trials</span> </caption> <col width="20%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <col width="15%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule" valign="top"> Adverse Reactions</th><th align="center" class="Botrule Rrule" valign="top">Placebo <br/> N=382% </th><th align="center" class="Botrule Rrule" valign="top">Rosuvastatin <br/> 5 mg <br/> N=291% </th><th align="center" class="Botrule Rrule" valign="top">Rosuvastatin <br/> 10 mg <br/> N=283% </th><th align="center" class="Botrule Rrule" valign="top">Rosuvastatin <br/> 20 mg <br/> N=64% </th><th align="center" class="Botrule Rrule" valign="top">Rosuvastatin <br/> 40 mg <br/> N=106% </th><th align="center" class="Botrule Rrule" valign="top">Total Rosuvastatin <br/> 5 mg to 40 mg <br/> N=744% </th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" valign="middle"> Headache</td><td align="center" class="Botrule Rrule" valign="middle">5.0</td><td align="center" class="Botrule Rrule" valign="middle">5.5</td><td align="center" class="Botrule Rrule" valign="middle">4.9</td><td align="center" class="Botrule Rrule" valign="middle">3.1</td><td align="center" class="Botrule Rrule" valign="middle">8.5</td><td align="center" class="Botrule Rrule" valign="middle">5.5</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="middle"> Nausea</td><td align="center" class="Botrule Rrule" valign="middle">3.1</td><td align="center" class="Botrule Rrule" valign="middle">3.8</td><td align="center" class="Botrule Rrule" valign="middle">3.5</td><td align="center" class="Botrule Rrule" valign="middle">6.3</td><td align="center" class="Botrule Rrule" valign="middle">0</td><td align="center" class="Botrule Rrule" valign="middle">3.4</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="middle"> Myalgia</td><td align="center" class="Botrule Rrule" valign="middle">1.3</td><td align="center" class="Botrule Rrule" valign="middle">3.1</td><td align="center" class="Botrule Rrule" valign="middle">2.1</td><td align="center" class="Botrule Rrule" valign="middle">6.3</td><td align="center" class="Botrule Rrule" valign="middle">1.9</td><td align="center" class="Botrule Rrule" valign="middle">2.8</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="middle"> Asthenia</td><td align="center" class="Botrule Rrule" valign="middle">2.6</td><td align="center" class="Botrule Rrule" valign="middle">2.4</td><td align="center" class="Botrule Rrule" valign="middle">3.2</td><td align="center" class="Botrule Rrule" valign="middle">4.7</td><td align="center" class="Botrule Rrule" valign="middle">0.9</td><td align="center" class="Botrule Rrule" valign="middle">2.7</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="middle"> Constipation</td><td align="center" class="Botrule Rrule" valign="middle">2.4</td><td align="center" class="Botrule Rrule" valign="middle">2.1</td><td align="center" class="Botrule Rrule" valign="middle">2.1</td><td align="center" class="Botrule Rrule" valign="middle">4.7</td><td align="center" class="Botrule Rrule" valign="middle">2.8</td><td align="center" class="Botrule Rrule" valign="middle">2.4</td> </tr> </tbody> </table></div>

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; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.

In the METEOR study, patients were treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years. Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 3.

<div class="scrollingtable"><table width="50%"> <caption> <span>Table 3: Adverse Reactions Reported in ≥ 2% of Patients Treated with Rosuvastatin and &gt; Placebo in the METEOR Trial</span> </caption> <col width="40%"/> <col width="30%"/> <col width="40%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule Toprule" valign="top">Adverse Reactions</th><th align="center" class="Rrule Toprule" valign="top">Placebo <br/> N=281% </th><th align="center" class="Rrule Toprule" valign="top">Rosuvastatin 40 mg <br/> N=700% </th> </tr> </thead> <tfoot> <tr class="First Last"> <td colspan="3"><span class="Sup">1</span>Frequency recorded as abnormal laboratory value. </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule Toprule" valign="top">Myalgia</td><td align="center" class="Rrule Toprule" valign="top">12.1</td><td align="center" class="Rrule Toprule" valign="top">12.7</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Arthralgia</td><td align="center" class="Rrule Toprule" valign="top">7.1</td><td align="center" class="Rrule Toprule" valign="top">10.1</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Headache</td><td align="center" class="Rrule Toprule" valign="top">5.3</td><td align="center" class="Rrule Toprule" valign="top">6.4</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Dizziness</td><td align="center" class="Rrule Toprule" valign="top">2.8</td><td align="center" class="Rrule Toprule" valign="top">4.0</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Increased CPK</td><td align="center" class="Rrule Toprule" valign="top">0.7</td><td align="center" class="Rrule Toprule" valign="top">2.6</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Abdominal pain</td><td align="center" class="Rrule Toprule" valign="top">1.8</td><td align="center" class="Rrule Toprule" valign="top">2.4</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule Toprule" valign="top">ALT greater than 3x ULN <span class="Sup">1</span></td><td align="center" class="Rrule Toprule" valign="top">0.7</td><td align="center" class="Rrule Toprule" valign="top">2.2</td> </tr> </tbody> </table></div>

In the JUPITER study, patients were treated with rosuvastatin 20 mg (n=8901) or placebo (n=8901) for a mean duration of 2 years. In JUPITER, 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 Clinical Studies (14)].

Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 4.

<div class="scrollingtable"><table width="50%"> <caption> <span>Table 4: Adverse Reactions Reported in ≥ 2% of Patients Treated with Rosuvastatin and &gt; Placebo in the JUPITER Trial</span> </caption> <col width="40%"/> <col width="30%"/> <col width="30%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule Toprule" valign="top">Adverse Reactions</th><th align="center" class="Rrule Toprule" valign="top">Placebo <br/> N=8901% </th><th align="center" class="Rrule Toprule" valign="top">Rosuvastatin 20 mg <br/> N=8901% </th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule Toprule" valign="top">Myalgia</td><td align="center" class="Rrule Toprule" valign="top">6.6</td><td align="center" class="Rrule Toprule" valign="top">7.6</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Arthralgia</td><td align="center" class="Rrule Toprule" valign="top">3.2</td><td align="center" class="Rrule Toprule" valign="top">3.8</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Constipation</td><td align="center" class="Rrule Toprule" valign="top">3.0</td><td align="center" class="Rrule Toprule" valign="top">3.3</td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Diabetes mellitus</td><td align="center" class="Rrule Toprule" valign="top">2.3</td><td align="center" class="Rrule Toprule" valign="top">2.8</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule Toprule" valign="top">Nausea</td><td align="center" class="Rrule Toprule" valign="top">2.3</td><td align="center" class="Rrule Toprule" valign="top">2.4</td> </tr> </tbody> </table></div>

Pediatric Patients with HeFH

In a 12-week controlled study in pediatric patients 10 to 17 years of age with HeFH with rosuvastatin 5 mg to 20 mg daily [see Use in Specific Populations (8.4)and Clinical Studies (14)] , elevations in serum CK greater than 10 x ULN were observed more frequently in rosuvastatin treated patients compared with patients receiving placebo. Four of 130 (3%) patients treated with Rosuvastatin (2 treated with 10 mg and 2 treated with 20 mg) had increased CK greater than 10 x ULN, compared to 0 of 46 patients on placebo.

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

Blood Disorders:thrombocytopenia

Hepatobiliary Disorders:hepatitis, jaundice, fatal and non-fatal hepatic failure

Musculoskeletal Disorders:arthralgia, rare reports of immune-mediated necrotizing myopathy associated with statin use

Nervous System Disorders:peripheral neuropathy, rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, and confusion) associated with the use of 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). There have been rare reports of new-onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered.

Psychiatric Disorders:depression, sleep disorders (including insomnia and nightmares)

Reproductive System and Breast Disorders:gynecomastia

Respiratory Disorders:interstitial lung disease

Skin and Subcutaneous Tissue Disorders:drug reaction with eosinophilia and systemic symptoms (DRESS), lichenoid drug eruption

Rosuvastatin is a substrate of CYP2C9 and transporters (such as OATP1B1, BCRP). Rosuvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP2C9 and transporters. Table 5 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with rosuvastatin and instructions for preventing or managing them [see Warnings and Precautions (5.1)and Clinical Pharmacology (12.3)] .

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 5: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin Tablets</span> </caption> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="50%"/> <col align="center" valign="top" width="30%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Cyclosporine</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with rosuvastatin.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">If used concomitantly, do not exceed a dose of rosuvastatin 5 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Teriflunomide</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Teriflunomide increased rosuvastatin exposure more than 2.5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking teriflunomide, do not exceed a dose of rosuvastatin 10 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Enasidenib</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Enasidenib increased rosuvastatin exposure more than 2.4-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking enasidenib, do not exceed a dose of rosuvastatin 10 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Capmatinib</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Capmatinib increased rosuvastatin exposure more than 2.1-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking capmatinib, do not exceed a dose of rosuvastatin 10 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Fostamatinib</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Fostamatinib increased rosuvastatin exposure more than 2.0-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking fostamatinib, do not exceed a dose of rosuvastatin 20 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Febuxostat</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Febuxostat increased rosuvastatin exposure more than 1.9-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking febuxostat, do not exceed a dose of rosuvastatin 20 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Gemfibrozil</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with rosuvastatin.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Avoid concomitant use of gemfibrozil with rosuvastatin. If used concomitantly, initiate rosuvastatin at 5 mg once daily and do not exceed a dose of rosuvastatin 10 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Tafamidis</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Tafamidis significantly increased rosuvastatin exposure and tafamidis may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of tafamidis with rosuvastatin.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Avoid concomitant use of tafamidis with rosuvastatin. If used concomitantly, initiate rosuvastatin at 5 mg once daily and do not exceed a dose of rosuvastatin 20 mg once daily. Monitor for signs of myopathy and rhabdomyolysis if used concomitantly with rosuvastatin.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Anti-Viral Medications</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> <ul class="Disc"> <li>Sofosbuvir/velpatasvir/voxilaprevir</li> <li>Ledipasvir/sofosbuvir</li> </ul> </td><td align="left" class="Botrule Lrule Rrule" valign="middle">Avoid concomitant use with rosuvastatin.</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"></td><td align="left" class="Botrule Rrule" valign="top"> <ul class="Disc"> <li>Simeprevir</li> <li>Dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>Elbasvir/grazoprevir</li> <li>Sofosbuvir/velpatasvir</li> <li>Glecaprevir/pibrentasvir</li> <li>Atazanavir/ritonavir</li> <li>Lopinavir/ritonavir</li> </ul> </td><td align="left" class="Botrule Lrule Rrule" valign="middle">Initiate with rosuvastatin 5 mg once daily, and do not exceed a dose of rosuvastatin 10 <br/> mg once daily. </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Darolutamide</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking darolutamide, do not exceed a dose of rosuvastatin 5 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Regorafenib</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">In patients taking regorafenib, do not exceed a dose of rosuvastatin 10 mg once daily.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Fenofibrates (e.g., fenofibrate and fenofibric acid)</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with rosuvastatin.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Consider if the benefit of using fibrates concomitantly with rosuvastatin outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Niacin</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Cases of myopathy and rhabdomyolysis have occurred with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with rosuvastatin.</td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Consider if the benefit of using lipid-modifying doses (≥1 g/day) of niacin concomitantly with rosuvastatin outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Colchicine</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with rosuvastatin.</td> </tr> <tr class="Last"> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top">Consider if the benefit of using colchicine concomitantly with rosuvastatin outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.</td> </tr> </tbody> </table></div>

Table 6 presents drug interactions that may decrease the efficacy of rosuvastatin and instructions for preventing or managing them.

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 6: Drug Interactions that Decrease the Efficacy of Rosuvastatin</span> </caption> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="80%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Antacids</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">Concomitant aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>] </span>. </td> </tr> <tr class="Last"> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">In patients taking antacid, administer rosuvastatin at least 2 hours after the antacid.</td> </tr> </tbody> </table></div>

Table 7 presents rosuvastatin’s effect on other drugs and instructions for preventing or managing them.

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 7: Rosuvastatin Effects on Other Drugs</span> </caption> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="80%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Warfarin</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Clinical Impact:</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">Rosuvastatin significantly increased the INR in patients receiving warfarin <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>] </span>. </td> </tr> <tr class="Last"> <td align="right" class="Botrule Lrule Rrule" valign="middle"><span class="Italics">Intervention:</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">In patients taking warfarin, obtain an INR before starting rosuvastatin and frequently enough after initiation, dose titration or discontinuation to ensure that no significant alteration in INR occurs. Once the INR is stable, monitor INR at regularly recommended intervals.</td> </tr> </tbody> </table></div>

Risk Summary

Discontinue rosuvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient.

Rosuvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, rosuvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients.

Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with rosuvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) .

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (MRHD) of 40 mg/day, based on AUC and body surface area (mg/m 2), respectively (see Data) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Human Data

A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity scorebased methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.

Animal Data

In female rats given 5 mg/kg/day, 15 mg/kg/day 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 mg/kg/day, 10 mg/kg/day 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 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area).

Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. In rabbits, fetal tissue distribution was 25% of maternal plasma concentration after a single oral gavage dose of 1 mg/kg on gestation day 18.

Risk Summary

Limited data from case reports in published literature indicate that 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. Statins, including rosuvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant.

Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with rosuvastatin [see Use in Specific Populations (8.1)and Clinical Pharmacology (12.1)] .

The safety and effectiveness of rosuvastatin as an adjunct to diet to reduce LDL-C have been established in pediatric patients 8 years of age and older with HeFH. Use of rosuvastatin for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with HeFH and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with HeFH [see Clinical Studies (14)] . In the 1-year trial with a 12-week controlled phase, there was no detectable effect of rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in patients aged 10 to 17 years.

The safety and effectiveness of rosuvastatin as an adjunct to other LDL-C-lowering therapies to reduce LDL-C have been established pediatric patients 7 years of age and older with HoFH. Use of rosuvastatin for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with HoFH [see Clinical Studies (14)] .

The safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with HeFH, younger than 7 years of age with HoFH, or in pediatric patients with other types of hyperlipidemia (other than HeFH or HoFH).

Of the 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.

Advanced age (≥65 years) is a risk factor for rosuvastatin-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving rosuvastatin for the increased risk of myopathy [see Warnings and Precautions (5.1)] .

Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CL cr≥ 30 mL/min/1.73 m 2). Exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (CL cr< 30 mL/min/1.73 m 2) who are not receiving hemodialysis [ see Clinical Pharmacology (12.3)].

Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. In patients with severe renal impairment not on hemodialysis, the recommended starting dosage is 5 mg daily and should not exceed 10 mg daily [see Dosage and Administration (2.5)and Warnings and Precautions (5.1)] .

Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [ see Contraindications (4), Warning and Precautions (5.3)and Clinical Pharmacology (12.3)].

Pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects when compared with White controls. Adjust the rosuvastatin dosage in Asian patients [ see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)].

No specific antidotes for rosuvastatin are known. Hemodialysis does not significantly enhance clearance of rosuvastatin. In the event of overdose, consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

{ "type": "p", "children": [], "text": "No specific antidotes for rosuvastatin are known. Hemodialysis does not significantly enhance clearance of rosuvastatin. In the event of overdose, consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations." }

Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)-reductase inhibitor.

{ "type": "p", "children": [], "text": "Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)-reductase inhibitor." }

The chemical name for rosuvastatin calcium, USP 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:

{ "type": "p", "children": [], "text": "The chemical name for rosuvastatin calcium, USP 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 empirical formula for rosuvastatin calcium is (C 22H 27FN 3O 6S) 2Ca and the molecular weight is 1001.14. Rosuvastatin calcium, USP is a white to almost white amorphous powder that is sparingly soluble in water and methanol, and slightly soluble in ethanol. Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 1.4 at pH of 7.0.

{ "type": "p", "children": [], "text": "The empirical formula for rosuvastatin calcium is (C\n \n 22H\n \n 27FN\n \n 3O\n \n 6S)\n \n 2Ca and the molecular weight is 1001.14. Rosuvastatin calcium, USP is a white to almost white amorphous powder that is sparingly soluble in water and methanol, and slightly soluble in ethanol. Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 1.4 at pH of 7.0.\n\n " }

Rosuvastatin tablets, USP for oral use contain rosuvastatin 5 mg, 10 mg, 20 mg, or 40 mg (equivalent to 5.2 mg, 10.4 mg, 20.8 mg, and 41.6 mg rosuvastatin calcium, USP) and the following inactive ingredients: Each tablet contains: crospovidone, dibasic calcium phosphate dihydrate, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, red ferric oxide, triacetin and titanium dioxide.

{ "type": "p", "children": [], "text": "Rosuvastatin tablets, USP for oral use contain rosuvastatin 5 mg, 10 mg, 20 mg, or 40 mg (equivalent to 5.2 mg, 10.4 mg, 20.8 mg, and 41.6 mg rosuvastatin calcium, USP) and the following inactive ingredients: Each tablet contains: crospovidone, dibasic calcium phosphate dihydrate, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, red ferric oxide, triacetin and titanium dioxide." }

Rosuvastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol.

Inhibition of HMG-CoA reductase by rosuvastatin accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins. The maximum LDL-C reduction of rosuvastatin is usually achieved by 4 weeks and is maintained after that.

Absorption

In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both C maxand AUC increased in approximate proportion to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%. The AUC of rosuvastatin does not differ following evening or morning drug administration.

Effect of food

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

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.

Elimination

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 vitrostudies 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%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route. The elimination half-life of rosuvastatin is approximately 19 hours.

Specific Populations

Geriatric Patients

There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥65 years ).

Pediatric Patients

In a population pharmacokinetic analysis of two pediatric trials involving patients with HeFH 10 years to 17 years of age and 8 years to 17 years of age, respectively, rosuvastatin exposure appeared comparable to or lower than rosuvastatin exposure in adult patients.

Male and Female Patients

There were no differences in plasma concentrations of rosuvastatin between males and females.

Racial or Ethnic Groups

A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among White, Hispanic or Latino ethnicity, 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 C max) in Asian subjects when compared with a White control group.

Patients with Renal Impairment

Mild to moderate renal impairment (CL cr≥ 30 mL/min/1.73 m 2) 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 m 2) not receiving hemodialysis compared with healthy subjects (CL cr> 80 mL/min/1.73 m 2).

Steady-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 Impairment

In patients with chronic alcohol liver disease, plasma concentrations of rosuvastatin were modestly increased.

In patients with Child-Pugh A disease, C maxand AUC were increased by 60% and 5%, respectively, as compared with patients with normal liver function. In patients with Child-Pugh B disease, C maxand AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.

Drug Interaction Studies

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 tablets with medications that are inhibitors of these transporter proteins (e.g. cyclosporine, certain HIV protease inhibitors [see Dosage and Administration (2.6)and Drug Interactions (7.1)] and ticagrelor [see Drug Interactions (7.1)]) may result in increased rosuvastatin plasma concentrations.

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 8: Effect of Coadministered Drugs on Rosuvastatin Systemic Exposure</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <tfoot> <tr class="First"> <td align="left" colspan="5">QD=Once daily, BID=Twice daily, TID=Three times daily, QID=Four times daily</td> </tr> <tr> <td align="left" colspan="5"><span class="Sup">1</span>Single dose unless otherwise noted. </td> </tr> <tr> <td align="left" colspan="5"><span class="Sup">2</span>Clinically significant [ see Dosage and Administration (2) and Warnings and Precautions (5)] </td> </tr> <tr class="Last"> <td align="left" colspan="5"><span class="Sup">3</span>Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7 = 30% decrease, 11=11-fold increase in exposure) </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" valign="top"><span class="Bold">Coadministered drug and dosing regimen</span></td><td align="center" class="Rrule" colspan="3" valign="top"><span class="Bold">Rosuvastatin</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"></td><td align="left" class="Rrule" colspan="2" valign="top"><span class="Bold">Mean Ratio <br/> (ratio with/without <br/> coadministered drug) <br/> No Effect = 1.0 </span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"><span class="Bold">Dose (mg) <span class="Sup">1</span></span></td><td align="left" class="Rrule" valign="top"><span class="Bold">Change in AUC</span></td><td align="left" class="Rrule" valign="top"><span class="Bold">Change in C <span class="Sub">max</span></span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Sofosbuvir/velpatasvir/voxilaprevir <br/> (400 mg/100 mg/100 mg) + Voxilaprevir (100 mg) once daily for 15 days </td><td align="center" class="Rrule" valign="top">10mg, single dose</td><td align="left" class="Rrule" valign="top">7.39 <span class="Sup">2</span> <br/> (6.68 to 8.18) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">18.88 <span class="Sup">2</span> <br/> (16.23 to 21.96) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Cyclosporine – stable dose <br/> required (75 mg to 200 mg BID) </td><td align="center" class="Rrule" valign="top">10 mg, QD for <br/> 10 days </td><td align="center" class="Rrule" valign="bottom">7.1 <span class="Sup">2</span></td><td align="center" class="Rrule" valign="bottom">11 <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Darolutamide 600 mg BID, 5 days</td><td align="center" class="Rrule" valign="top">5 mg, single dose</td><td align="center" class="Rrule" valign="top">5.2 <span class="Sup">2</span></td><td align="center" class="Rrule" valign="top">~5 <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Regorafenib 160mg OD, 14 days</td><td align="center" class="Rrule" valign="top">5 mg, single dose</td><td align="center" class="Rrule" valign="top">3.8 <span class="Sup">2</span></td><td align="center" class="Rrule" valign="top">4.6 <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Atazanavir/ritonavir combination <br/> 300 mg/100 mg QD for 8 days </td><td align="center" class="Rrule" valign="top">10 mg</td><td align="center" class="Rrule" valign="top">3.1 <span class="Sup">2</span></td><td align="center" class="Rrule" valign="middle">7 <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Simeprevir 150 mg QD, 7 days</td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">2.8 <span class="Sup">2</span> <br/> (2.3-3.4) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">3.2 <span class="Sup">2</span> <br/> (2.6-3.9) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Velpatasvir 100 mg once daily</td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">2.69 <span class="Sup">2</span> <br/> (2.46-2.94) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2.61 <span class="Sup">2</span> <br/> (2.32-2.92) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Ombitasvir 25mg/paritaprevir <br/> 150mg/ritonavir 100mg <br/> +dasabuvir 400 mg BID </td><td align="center" class="Rrule" valign="top">5 mg, single dose</td><td align="left" class="Rrule" valign="top">2.59 <span class="Sup">2</span> <br/> (2.09-3.21) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">7.13 <span class="Sup">2</span> <br/> (5.11-9.96) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Teriflunomide</td><td align="center" class="Rrule" valign="top">Not available</td><td align="left" class="Rrule" valign="top">2.51 <span class="Sup">2</span></td><td align="left" class="Rrule" valign="top">2.65 <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Enasidenib 100 mg QD, 28 days</td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">2.44</td><td align="left" class="Rrule" valign="top">3.66</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Elbasvir 50mg/grazoprevir 200mg <br/> once daily </td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">2.26 <span class="Sup">2</span> <br/> (1.89-2.69) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">5.49 <span class="Sup">2</span> <br/> (4.29-7.04) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Glecaprevir 400mg/pibrentasvir <br/> 120 mg once daily </td><td align="center" class="Rrule" valign="top">5 mg, once daily</td><td align="left" class="Rrule" valign="top">2.15 <span class="Sup">2</span> <br/> (1.88-2.46) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">5.62 <span class="Sup">2</span> <br/> (4.80-6.59) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Lopinavir/ritonavir combination <br/> 400 mg/100 mg BID for 17 days </td><td align="center" class="Rrule" valign="top">20 mg, QD <br/> for 7 days </td><td align="left" class="Rrule" valign="top">2.1 <span class="Sup">2</span> <br/> (1.7-2.6) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">5 <span class="Sup">2</span> <br/> (3.4-6.4) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Capmatinib 400 mg BID</td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">2.08 <span class="Sup">2</span> <br/> (1.56-2.76) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">3.04 <span class="Sup">2</span> <br/> (2.36-3.92) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Fostamatinib 100 mg BID</td><td align="center" class="Rrule" valign="top">20 mg, single dose</td><td align="left" class="Rrule" valign="top">1.96 <span class="Sup">2</span> <br/> (1.77-2.15) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.88 <span class="Sup">2</span> <br/> (1.69-2.09) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Febuxostat 120 mg QD for 4 days</td><td align="center" class="Rrule" valign="top">10 mg, single dose</td><td align="left" class="Rrule" valign="top">1.9 <span class="Sup">2</span> <br/> (1.5-2.5) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2.1 <span class="Sup">2</span> <br/> (1.8-2.6) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Gemfibrozil 600 mg BID <br/> for 7 days </td><td align="center" class="Rrule" valign="top">80 mg</td><td align="left" class="Rrule" valign="top">1.9 <span class="Sup">2</span> <br/> (1.6-2.2) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2.2 <span class="Sup">2</span> <br/> (1.8-2.7) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Tafamidis 61 mg BID on Days 1 &amp; 2, followed by QD on Days 3 to 9</td><td align="center" class="Rrule" valign="top">10 mg</td><td align="left" class="Rrule" valign="top">1.97 <span class="Sup">2</span> <br/> (1.68-2.31) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.86 <span class="Sup">2</span> <br/> (1.59-2.16) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Eltrombopag 75 mg QD, 5 days</td><td align="center" class="Rrule" valign="top">10 mg</td><td align="left" class="Rrule" valign="top">1.6 <br/> (1.4-1.7) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2 <br/> (1.8-2.3) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Darunavir 600 mg/ritonavir <br/> 100 mg BID, 7 days </td><td align="center" class="Rrule" valign="top">10 mg, QD for 7 days</td><td align="left" class="Rrule" valign="top">1.5 <br/> (1.0-2.1) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2.4 <br/> (1.6-3.6) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Tipranavir/ritonavir combination <br/> 500 mg/200mg BID for 11 days </td><td align="center" class="Rrule" valign="top">10 mg</td><td align="left" class="Rrule" valign="top">1.4 <br/> (1.2-1.6) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">2.2 <br/> (1.8-2.7) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Dronedarone 400 mg BID</td><td align="center" class="Rrule" valign="top">10 mg</td><td align="left" class="Rrule" valign="top">1.4</td><td align="left" class="Rrule" valign="top"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Itraconazole 200 mg QD, 5 days</td><td align="center" class="Rrule" valign="top">10 mg or 80 mg</td><td align="left" class="Rrule" valign="top">1.4 <br/> (1.2-1.6) <span class="Sup">3</span> <br/> 1.3 <br/> (1.1-1.4) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.4 <br/> (1.2-1.5) <span class="Sup">3</span> <br/> 1.2 <br/> (0.9-1.4) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Ezetimibe 10 mg QD, 14 days</td><td align="center" class="Rrule" valign="middle">10 mg, QD for <br/> 14 days </td><td align="left" class="Rrule" valign="top">1.2 <br/> (0.9-1.6) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.2 <br/> (0.8-1.6) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Fosamprenavir/ritonavir <br/> 700 mg/100 mg BID for 7 days </td><td align="center" class="Rrule" valign="top">10 mg</td><td align="center" class="Rrule" valign="top">1.1</td><td align="left" class="Rrule" valign="top">1.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Fenofibrate 67 mg TID for 7 days</td><td align="center" class="Rrule" valign="top">10 mg</td><td align="center" class="Rrule" valign="top">↔</td><td align="left" class="Rrule" valign="top">1.2 <br/> (1.1-1.3) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Rifampicin 450 mg QD, 7 days</td><td align="center" class="Rrule" valign="top">20 mg</td><td align="center" class="Rrule" valign="top">↔</td><td align="center" class="Rrule" valign="top"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Aluminum &amp; magnesium <br/> hydroxide combination antacid <br/> Administered simultaneously <br/> Administered 2 hours apart </td><td align="center" class="Rrule" valign="top"> <br/> <br/> 40 mg <br/> 40 mg </td><td align="left" class="Rrule" valign="middle"> <br/> 0.5 <span class="Sup">2</span> <br/> (0.4-0.5) <span class="Sup">3</span> <br/> 0.8 <br/> (0.7-0.9) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="middle"> <br/> 0.5 <span class="Sup">2</span> <br/> (0.4-0.6) <span class="Sup">3</span> <br/> 0.8 <br/> (0.7-1.0) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Ketoconazole 200 mg BID for <br/> 7 days </td><td align="center" class="Rrule" valign="top">80 mg</td><td align="left" class="Rrule" valign="top">1.0 <br/> (0.8-1.2) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.0 <br/> (0.7-1.3) <span class="Sup">3</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">Fluconazole 200 mg QD for 11 <br/> days </td><td align="center" class="Rrule" valign="top">80 mg</td><td align="left" class="Rrule" valign="top">1.1 <br/> (1.0-1.3) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">1.1 <br/> (0.9-1.4) <span class="Sup">3</span></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" valign="top">Erythromycin 500 mg QID for 7 <br/> days </td><td align="center" class="Rrule" valign="top">80 mg</td><td align="left" class="Rrule" valign="top">0.8 <br/> (0.7-0.9) <span class="Sup">3</span></td><td align="left" class="Rrule" valign="top">0.7 <br/> (0.5-0.9) <span class="Sup">3</span></td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 9: Effect of Rosuvastatin Coadministration on Systemic Exposure to Other Drugs</span> </caption> <col align="left" valign="top" width="20%"/> <col align="center" valign="top" width="30%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <tfoot> <tr class="First"> <td align="left" colspan="4">EE = ethinyl estradiol, NG = norgestrel, QD=Once daily</td> </tr> <tr> <td align="left" colspan="4"><span class="Sup">1</span>Clinically significant pharmacodynamic effects [ see Drug Interactions (7.3)] </td> </tr> <tr class="Last"> <td align="left" colspan="4"><span class="Sup">2</span>Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7=30% decrease, 11=11-fold increase in exposure) </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" valign="top"><span class="Bold">Rosuvastatin <br/> Dosage Regimen </span></td><td align="left" class="Rrule" colspan="3" valign="top"><span class="Bold">Coadministered Drug</span> <br/> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"></td><td align="center" class="Rrule" colspan="2" valign="top"><span class="Bold">Mean Ratio <br/> (ratio with/without coadministered drug) <br/> No Effect = 1.0 </span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" valign="top"><span class="Bold">Name and Dose</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Change in AUC</span></td><td align="center" class="Rrule" valign="top"><span class="Bold">Change in C <span class="Sub">max</span></span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">40 mg QD for 10 days <br/> </td><td align="center" class="Rrule" valign="top">Warfarin <span class="Sup">1</span> <br/> 25 mg single dose <br/> </td><td align="center" class="Rrule" valign="top">R- Warfarin <br/> 1.0 <br/> (1.0 to 1.1) <span class="Sup">2</span> <br/> S-Warfarin <br/> 1.1 <br/> (1.0 to 1.1) <span class="Sup">2</span></td><td align="center" class="Rrule" valign="top">R-Warfarin <br/> 1.0 <br/> (0.9 to 1.0) <span class="Sup">2</span> <br/> S-Warfarin <br/> 1.0 <br/> (0.9 to 1.1) <span class="Sup">2</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="top">40 mg QD for 12 days</td><td align="center" class="Rrule" valign="top">Digoxin 0.5 mg single dose</td><td align="center" class="Rrule" valign="top">1.0 <br/> (0.9 to 1.2) <span class="Sup">2</span></td><td align="center" class="Rrule" valign="top">1.0 <br/> (0.9 to 1.2) <span class="Sup">2</span></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" valign="top">40 mg QD for 28 days <br/> </td><td align="center" class="Rrule" valign="top">Oral Contraceptive <br/> (ethinyl estradiol 0.035 mg &amp; norgestrel 0.180, 0.215 and 0.250 mg) QD for 21 Days </td><td align="center" class="Rrule" valign="top"> <br/> EE 1.3 <br/> (1.2 to 1.3) <span class="Sup">2</span> <br/> NG 1.3 <br/> (1.3 to 1.4) <span class="Sup">2</span></td><td align="center" class="Rrule" valign="top"> <br/> EE 1.3 <br/> (1.2 to 1.3) <span class="Sup">2</span> <br/> NG 1.2 <br/> (1.1 to 1.3) <span class="Sup">2</span></td> </tr> </tbody> </table></div>

Disposition of 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 ( SLCO1B1521T > C). The frequency of this genotype (i.e., SLCO1B1521 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.

In a 104-week carcinogenicity study in rats at dose levels of 2 mg/kg/day, 20 mg/kg/day 60 mg/kg/day, 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 mg/kg/day, 60 mg/kg/day, 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 typhimuriumand Escherichia coli, the mouse lymphoma assay, and the chromosomal aberration assay in Chinese hamster lung cells. Rosuvastatin was negative in the in vivomouse micronucleus test.

In rat fertility studies with oral gavage doses of 5 mg/kg/day, 15 mg/kg/day, 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.

Primary Prevention of CV Disease

{ "type": "p", "children": [], "text": "\nPrimary Prevention of CV Disease\n" }

In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of Atorvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL-C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Patients had a median baseline LDL-C of 108 mg/dL and hsCRP of 4.3 mg/L. Patients were randomly assigned to placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects.

{ "type": "p", "children": [], "text": "In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of Atorvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL-C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Patients had a median baseline LDL-C of 108 mg/dL and hsCRP of 4.3 mg/L. Patients were randomly assigned to placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects." }

The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure.

{ "type": "p", "children": [], "text": "The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure." }

Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see Figure 1). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL-C, HDL-C, and hsCRP levels.

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see\n \n Figure 1). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL-C, HDL-C, and hsCRP levels.\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Figure 1. Time to First Occurrence of Major CV Events in JUPITER</span> </caption> <col align="center" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure-01" src="/dailymed/image.cfm?name=figure-1.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<caption>\n<span>Figure 1. Time to First Occurrence of Major CV Events in JUPITER</span>\n</caption>\n<col align=\"center\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure-01\" src=\"/dailymed/image.cfm?name=figure-1.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442\"/></td>\n</tr>\n</tbody>\n</table></div>" }

The individual components of the primary end point are presented in Figure 3. rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to CV causes or hospitalizations for unstable angina.

{ "type": "p", "children": [], "text": "The individual components of the primary end point are presented in Figure 3. rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to CV causes or hospitalizations for unstable angina." }

Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects).

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects)." }

In a post-hoc subgroup analysis of JUPITER subjects (rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL-C) other than age, after adjustment for high HDL-C, there was no significant treatment benefit with rosuvastatin treatment.

{ "type": "p", "children": [], "text": "In a post-hoc subgroup analysis of JUPITER subjects (rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL-C) other than age, after adjustment for high HDL-C, there was no significant treatment benefit with rosuvastatin treatment." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Figure 2. Major CV Events by Treatment Group in JUPITER</span> </caption> <col align="center" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure-02" src="/dailymed/image.cfm?name=figure-2.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<caption>\n<span>Figure 2. Major CV Events by Treatment Group in JUPITER</span>\n</caption>\n<col align=\"center\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure-02\" src=\"/dailymed/image.cfm?name=figure-2.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442\"/></td>\n</tr>\n</tbody>\n</table></div>" }

At one year, rosuvastatin increased HDL-C and reduced LDL-C, hsCRP, total cholesterol and serum triglyceride levels (p<0.001 for all versus placebo).

{ "type": "p", "children": [], "text": "At one year, rosuvastatin increased HDL-C and reduced LDL-C, hsCRP, total cholesterol and serum triglyceride levels (p<0.001 for all versus placebo)." }

Primary Hyperlipidemia in Adults

{ "type": "p", "children": [], "text": "\nPrimary Hyperlipidemia in Adults\n" }

Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia.

{ "type": "p", "children": [], "text": "Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia." }

In a multicenter, double-blind, placebo-controlled study in patients with hyperlipidemia, rosuvastatin given as a single daily dose (5 to 40 mg) for 6 weeks significantly reduced Total-C, LDL-C, non-HDL-C, and ApoB, across the dose range (Table 10).

{ "type": "p", "children": [], "text": "In a multicenter, double-blind, placebo-controlled study in patients with hyperlipidemia, rosuvastatin given as a single daily dose (5 to 40 mg) for 6 weeks significantly reduced Total-C, LDL-C, non-HDL-C, and ApoB, across the dose range (Table 10)." }

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 10: Lipid-modifying Effect of Rosuvastatin in Adult Patients with Hyperlipidemia (Adjusted Mean % Change from Baseline at Week 6)</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule">Dose</th><th align="center" class="Botrule Rrule">N</th><th align="center" class="Botrule Rrule">Total-C</th><th align="center" class="Botrule Rrule" scope="row">LDL-C</th><th align="center" class="Botrule Rrule">Non-HDL-C</th><th align="center" class="Botrule Rrule">ApoB</th><th align="center" class="Botrule Rrule">TG</th><th align="center" class="Botrule Rrule">HDL-C</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule">Placebo</td><td align="center" class="Botrule Rrule">13</td><td align="center" class="Botrule Rrule">-5</td><td align="center" class="Botrule Rrule">-7</td><td align="center" class="Botrule Rrule">-7</td><td align="center" class="Botrule Rrule">-3</td><td align="center" class="Botrule Rrule">-3</td><td align="center" class="Botrule Rrule">3</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Rosuvastatin 5 mg</td><td align="center" class="Botrule Rrule">17</td><td align="center" class="Botrule Rrule">-33</td><td align="center" class="Botrule Rrule">-45</td><td align="center" class="Botrule Rrule">-44</td><td align="center" class="Botrule Rrule">-38</td><td align="center" class="Botrule Rrule">-35</td><td align="center" class="Botrule Rrule">13</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Rosuvastatin 10 mg</td><td align="center" class="Botrule Rrule">17</td><td align="center" class="Botrule Rrule">-36</td><td align="center" class="Botrule Rrule">-52</td><td align="center" class="Botrule Rrule">-48</td><td align="center" class="Botrule Rrule">-42</td><td align="center" class="Botrule Rrule">-10</td><td align="center" class="Botrule Rrule">14</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Rosuvastatin 20 mg</td><td align="center" class="Botrule Rrule">17</td><td align="center" class="Botrule Rrule">-40</td><td align="center" class="Botrule Rrule">-55</td><td align="center" class="Botrule Rrule">-51</td><td align="center" class="Botrule Rrule">-46</td><td align="center" class="Botrule Rrule">-23</td><td align="center" class="Botrule Rrule">8</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">Rosuvastatin 40 mg</td><td align="center" class="Botrule Rrule">18</td><td align="center" class="Botrule Rrule">-46</td><td align="center" class="Botrule Rrule">-63</td><td align="center" class="Botrule Rrule">-60</td><td align="center" class="Botrule Rrule">-54</td><td align="center" class="Botrule Rrule">-28</td><td align="center" class="Botrule Rrule">10</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"80%\">\n<caption>\n<span>Table 10: Lipid-modifying Effect of Rosuvastatin in Adult Patients with Hyperlipidemia (Adjusted Mean % Change from Baseline at Week 6)</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule\">Dose</th><th align=\"center\" class=\"Botrule Rrule\">N</th><th align=\"center\" class=\"Botrule Rrule\">Total-C</th><th align=\"center\" class=\"Botrule Rrule\" scope=\"row\">LDL-C</th><th align=\"center\" class=\"Botrule Rrule\">Non-HDL-C</th><th align=\"center\" class=\"Botrule Rrule\">ApoB</th><th align=\"center\" class=\"Botrule Rrule\">TG</th><th align=\"center\" class=\"Botrule Rrule\">HDL-C</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Placebo</td><td align=\"center\" class=\"Botrule Rrule\">13</td><td align=\"center\" class=\"Botrule Rrule\">-5</td><td align=\"center\" class=\"Botrule Rrule\">-7</td><td align=\"center\" class=\"Botrule Rrule\">-7</td><td align=\"center\" class=\"Botrule Rrule\">-3</td><td align=\"center\" class=\"Botrule Rrule\">-3</td><td align=\"center\" class=\"Botrule Rrule\">3</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Rosuvastatin 5 mg</td><td align=\"center\" class=\"Botrule Rrule\">17</td><td align=\"center\" class=\"Botrule Rrule\">-33</td><td align=\"center\" class=\"Botrule Rrule\">-45</td><td align=\"center\" class=\"Botrule Rrule\">-44</td><td align=\"center\" class=\"Botrule Rrule\">-38</td><td align=\"center\" class=\"Botrule Rrule\">-35</td><td align=\"center\" class=\"Botrule Rrule\">13</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Rosuvastatin 10 mg</td><td align=\"center\" class=\"Botrule Rrule\">17</td><td align=\"center\" class=\"Botrule Rrule\">-36</td><td align=\"center\" class=\"Botrule Rrule\">-52</td><td align=\"center\" class=\"Botrule Rrule\">-48</td><td align=\"center\" class=\"Botrule Rrule\">-42</td><td align=\"center\" class=\"Botrule Rrule\">-10</td><td align=\"center\" class=\"Botrule Rrule\">14</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Rosuvastatin 20 mg</td><td align=\"center\" class=\"Botrule Rrule\">17</td><td align=\"center\" class=\"Botrule Rrule\">-40</td><td align=\"center\" class=\"Botrule Rrule\">-55</td><td align=\"center\" class=\"Botrule Rrule\">-51</td><td align=\"center\" class=\"Botrule Rrule\">-46</td><td align=\"center\" class=\"Botrule Rrule\">-23</td><td align=\"center\" class=\"Botrule Rrule\">8</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Rosuvastatin 40 mg</td><td align=\"center\" class=\"Botrule Rrule\">18</td><td align=\"center\" class=\"Botrule Rrule\">-46</td><td align=\"center\" class=\"Botrule Rrule\">-63</td><td align=\"center\" class=\"Botrule Rrule\">-60</td><td align=\"center\" class=\"Botrule Rrule\">-54</td><td align=\"center\" class=\"Botrule Rrule\">-28</td><td align=\"center\" class=\"Botrule Rrule\">10</td>\n</tr>\n</tbody>\n</table></div>" }

Rosuvastatin was compared with the statins (atorvastatin, simvastatin, and pravastatin) in a multicenter, open-label, dose-ranging study of 2,240 patients with hyperlipidemia or mixed dyslipidemia. After randomization, patients were treated for 6 weeks with a single daily dose of either rosuvastatin, atorvastatin, simvastatin, or pravastatin (See Figure 3and Table 11).

{ "type": "p", "children": [], "text": "Rosuvastatin was compared with the statins (atorvastatin, simvastatin, and pravastatin) in a multicenter, open-label, dose-ranging study of 2,240 patients with hyperlipidemia or mixed dyslipidemia. After randomization, patients were treated for 6 weeks with a single daily dose of either rosuvastatin, atorvastatin, simvastatin, or pravastatin (See\n \n Figure 3and\n \n Table 11).\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Figure 3. Percent LDL-C Change by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin at Week 6 in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia</span> </caption> <col align="center" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure-02" src="/dailymed/image.cfm?name=figure-3.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<caption>\n<span>Figure 3. Percent LDL-C Change by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin at Week 6 in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia</span>\n</caption>\n<col align=\"center\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure-02\" src=\"/dailymed/image.cfm?name=figure-3.jpg&amp;setid=ab8f6264-cf12-4523-92f1-2bd60b3da442\"/></td>\n</tr>\n</tbody>\n</table></div>" }

Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDL-C: 189 mg/dL

{ "type": "p", "children": [], "text": "Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDL-C: 189 mg/dL" }

<div class="scrollingtable"><table width="70%"> <caption> <span>Table 11: Percent Change in LDL-C by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin From Baseline to Week 6 (LS MEAN <span class="Sup">1</span>) in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia (Sample Sizes Ranging from 156–167 Patients Per Group) </span> </caption> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <thead> <tr class="First"> <th align="center" class="Botrule Lrule Rrule"></th><th align="left" class="Botrule Rrule" colspan="4">Treatment Daily Dose</th> </tr> <tr class="Last"> <th align="left" class="Botrule Lrule Rrule">Treatment</th><th align="center" class="Botrule Rrule">10 mg</th><th align="center" class="Botrule Rrule">20 mg</th><th align="center" class="Botrule Rrule">40 mg</th><th align="center" class="Botrule Rrule">80 mg</th> </tr> </thead> <tfoot> <tr class="First"> <td align="left" colspan="3"><span class="Sup">1</span>Corresponding standard errors are approximately 1.00. </td> </tr> <tr> <td align="left" colspan="5"><span class="Sup">2</span>Rosuvastatin 10 mg reduced LDL-C significantly more than atorvastatin 10 mg; pravastatin 10 mg, 20 mg, and 40 mg; simvastatin 10 mg, 20 mg, and 40 mg. (p&lt;0.002) </td> </tr> <tr> <td align="left" colspan="5"><span class="Sup">3</span>Rosuvastatin 20 mg reduced LDL-C significantly more than atorvastatin 20 mg and 40 mg; pravastatin 20 mg and 40 mg; simvastatin 20 mg, 40 mg, and 80 mg. (p&lt;0.002) </td> </tr> <tr class="Last"> <td align="left" colspan="5"><span class="Sup">4</span>Rosuvastatin 40 mg reduced LDL-C significantly more than atorvastatin 40 mg; pravastatin 40 mg; simvastatin 40 mg, and 80 mg. (p&lt;0.002) </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule">Rosuvastatin</td><td align="center" class="Botrule Rrule">-46 <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-52 <span class="Sup">3</span></td><td align="center" class="Botrule Rrule">-55 <span class="Sup">4</span></td><td align="center" class="Botrule Rrule">---</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Atorvastatin</td><td align="center" class="Botrule Rrule">-37</td><td align="center" class="Botrule Rrule">-43</td><td align="center" class="Botrule Rrule">-48</td><td align="center" class="Botrule Rrule">-51</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Simvastatin</td><td align="center" class="Botrule Rrule">-28</td><td align="center" class="Botrule Rrule">-35</td><td align="center" class="Botrule Rrule">-39</td><td align="center" class="Botrule Rrule">-46</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">Pravastatin</td><td align="center" class="Botrule Rrule">-20</td><td align="center" class="Botrule Rrule">-24</td><td align="center" class="Botrule Rrule">-30</td><td align="center" class="Botrule Rrule">---</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"70%\">\n<caption>\n<span>Table 11: Percent Change in LDL-C by Dose of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin From Baseline to Week 6 (LS MEAN\n \n <span class=\"Sup\">1</span>) in Adult Patients with Hyperlipidemia or Mixed Dyslipidemia (Sample Sizes Ranging from 156–167 Patients Per Group)\n \n </span>\n</caption>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<thead>\n<tr class=\"First\">\n<th align=\"center\" class=\"Botrule Lrule Rrule\"></th><th align=\"left\" class=\"Botrule Rrule\" colspan=\"4\">Treatment Daily Dose</th>\n</tr>\n<tr class=\"Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule\">Treatment</th><th align=\"center\" class=\"Botrule Rrule\">10 mg</th><th align=\"center\" class=\"Botrule Rrule\">20 mg</th><th align=\"center\" class=\"Botrule Rrule\">40 mg</th><th align=\"center\" class=\"Botrule Rrule\">80 mg</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"3\"><span class=\"Sup\">1</span>Corresponding standard errors are approximately 1.00.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"5\"><span class=\"Sup\">2</span>Rosuvastatin 10 mg reduced LDL-C significantly more than atorvastatin 10 mg; pravastatin 10 mg, 20 mg, and 40 mg; simvastatin 10 mg, 20 mg, and 40 mg. (p&lt;0.002)\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"5\"><span class=\"Sup\">3</span>Rosuvastatin 20 mg reduced LDL-C significantly more than atorvastatin 20 mg and 40 mg; pravastatin 20 mg and 40 mg; simvastatin 20 mg, 40 mg, and 80 mg. (p&lt;0.002)\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"5\"><span class=\"Sup\">4</span>Rosuvastatin 40 mg reduced LDL-C significantly more than atorvastatin 40 mg; pravastatin 40 mg; simvastatin 40 mg, and 80 mg. (p&lt;0.002)\n \n </td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Rosuvastatin</td><td align=\"center\" class=\"Botrule Rrule\">-46\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-52\n \n <span class=\"Sup\">3</span></td><td align=\"center\" class=\"Botrule Rrule\">-55\n \n <span class=\"Sup\">4</span></td><td align=\"center\" class=\"Botrule Rrule\">---</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Atorvastatin</td><td align=\"center\" class=\"Botrule Rrule\">-37</td><td align=\"center\" class=\"Botrule Rrule\">-43</td><td align=\"center\" class=\"Botrule Rrule\">-48</td><td align=\"center\" class=\"Botrule Rrule\">-51</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Simvastatin</td><td align=\"center\" class=\"Botrule Rrule\">-28</td><td align=\"center\" class=\"Botrule Rrule\">-35</td><td align=\"center\" class=\"Botrule Rrule\">-39</td><td align=\"center\" class=\"Botrule Rrule\">-46</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Pravastatin</td><td align=\"center\" class=\"Botrule Rrule\">-20</td><td align=\"center\" class=\"Botrule Rrule\">-24</td><td align=\"center\" class=\"Botrule Rrule\">-30</td><td align=\"center\" class=\"Botrule Rrule\">---</td>\n</tr>\n</tbody>\n</table></div>" }

Slowing of the Progression of Atherosclerosis

{ "type": "p", "children": [], "text": "\nSlowing of the Progression of Atherosclerosis\n" }

In the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR)study, the effect of therapy with rosuvastatin on carotid atherosclerosis was assessed by B-mode ultrasonography in patients with elevated LDL-C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical atherosclerosis as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 adult patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to rosuvastatin 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with rosuvastatin and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, – 0.0093; p<0.0001).

{ "type": "p", "children": [], "text": "\nIn the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR)study, the effect of therapy with rosuvastatin on carotid atherosclerosis was assessed by B-mode ultrasonography in patients with elevated LDL-C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical atherosclerosis as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 adult patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to rosuvastatin 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with rosuvastatin and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, – 0.0093; p<0.0001).\n\n " }

The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p<0.0001). The annualized rate of change from baseline for the group treated with rosuvastatin was -0.0014 mm/year (p=0.32).

{ "type": "p", "children": [], "text": "The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p<0.0001). The annualized rate of change from baseline for the group treated with rosuvastatin was -0.0014 mm/year (p=0.32)." }

At an individual patient level in the group treated with rosuvastatin, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group.

{ "type": "p", "children": [], "text": "At an individual patient level in the group treated with rosuvastatin, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group." }

HeFH in Adults

{ "type": "p", "children": [], "text": "\nHeFH in Adults\n" }

In a study of adult patients with HeFH (baseline mean LDL of 291 mg/dL), patients were randomized to rosuvastatin 20 mg or atorvastatin 20 mg. The dose was increased at 6-week intervals. Significant LDL-C reductions from baseline were seen at each dose in both treatment groups (Table 12).

{ "type": "p", "children": [], "text": "In a study of adult patients with HeFH (baseline mean LDL of 291 mg/dL), patients were randomized to rosuvastatin 20 mg or atorvastatin 20 mg. The dose was increased at 6-week intervals. Significant LDL-C reductions from baseline were seen at each dose in both treatment groups (Table 12)." }

<div class="scrollingtable"><table width="50%"> <caption> <span>Table 12: LDL-C Percent Change from Baseline</span> </caption> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="40%"/> <col align="center" valign="top" width="40%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4"><span class="Sup">1</span>LS Means are least square means adjusted for baseline LDL-C </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <th align="center" class="Botrule Lrule Rrule"></th><th align="center" class="Botrule Lrule Rrule"></th><th align="left" class="Botrule Rrule">Rosuvastatin (n=435) <br/> LS Mean <span class="Sup">1</span>(95%CI) </th><th align="left" class="Botrule Rrule">Atorvastatin (n=187) <br/> LS Mean <span class="Sup">1</span>(95% CI) </th> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Week 6</td><td align="left" class="Botrule Rrule">20 mg</td><td align="left" class="Botrule Rrule">-47% (-49%, -46%)</td><td align="left" class="Botrule Rrule">-38% (-40%, -36%)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Week 12</td><td align="left" class="Botrule Rrule">40 mg</td><td align="left" class="Botrule Rrule">-55% (-57%, -54%)</td><td align="left" class="Botrule Rrule">-47% (-49%, -45%)</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">Week 18</td><td align="left" class="Botrule Rrule">80 mg</td><td align="left" class="Botrule Rrule">NA</td><td align="left" class="Botrule Rrule">-52% (-54%, -50%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"50%\">\n<caption>\n<span>Table 12: LDL-C Percent Change from Baseline</span>\n</caption>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<col align=\"center\" valign=\"top\" width=\"40%\"/>\n<col align=\"center\" valign=\"top\" width=\"40%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"4\"><span class=\"Sup\">1</span>LS Means are least square means adjusted for baseline LDL-C\n \n </td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<th align=\"center\" class=\"Botrule Lrule Rrule\"></th><th align=\"center\" class=\"Botrule Lrule Rrule\"></th><th align=\"left\" class=\"Botrule Rrule\">Rosuvastatin (n=435) \n <br/> LS Mean\n \n <span class=\"Sup\">1</span>(95%CI)\n \n </th><th align=\"left\" class=\"Botrule Rrule\">Atorvastatin (n=187) \n <br/> LS Mean\n \n <span class=\"Sup\">1</span>(95% CI)\n \n </th>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Week 6</td><td align=\"left\" class=\"Botrule Rrule\">20 mg</td><td align=\"left\" class=\"Botrule Rrule\">-47% (-49%, -46%)</td><td align=\"left\" class=\"Botrule Rrule\">-38% (-40%, -36%)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Week 12</td><td align=\"left\" class=\"Botrule Rrule\">40 mg</td><td align=\"left\" class=\"Botrule Rrule\">-55% (-57%, -54%)</td><td align=\"left\" class=\"Botrule Rrule\">-47% (-49%, -45%)</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Week 18</td><td align=\"left\" class=\"Botrule Rrule\">80 mg</td><td align=\"left\" class=\"Botrule Rrule\">NA</td><td align=\"left\" class=\"Botrule Rrule\">-52% (-54%, -50%)</td>\n</tr>\n</tbody>\n</table></div>" }

HeFH in Pediatric Patients

{ "type": "p", "children": [], "text": "\nHeFH in Pediatric Patients\n" }

In a double-blind, randomized, multicenter, placebo-controlled, 12-week study, 176 (97 male and 79 female) pediatric patients with HeFH were randomized to rosuvastatin 5 mg, 10 mg or 20 mg or placebo daily. Patients ranged in age from 10 to 17 years (median age of 14 years) with approximately 30% of the patients 10 to 13 years and approximately 17%, 18%, 40%, and 25% at Tanner stages II, III, IV, and V, respectively. Females were at least 1-year postmenarche. Mean LDL-C at baseline was 233 mg/dL (range of 129 to 399). The 12-week double-blind phase was followed by a 40 week open-label dose-titration phase, where all patients (n=173) received 5 mg, 10 mg or 20 mg rosuvastatin daily.

{ "type": "p", "children": [], "text": "In a double-blind, randomized, multicenter, placebo-controlled, 12-week study, 176 (97 male and 79 female) pediatric patients with HeFH were randomized to rosuvastatin 5 mg, 10 mg or 20 mg or placebo daily. Patients ranged in age from 10 to 17 years (median age of 14 years) with approximately 30% of the patients 10 to 13 years and approximately 17%, 18%, 40%, and 25% at Tanner stages II, III, IV, and V, respectively. Females were at least 1-year postmenarche. Mean LDL-C at baseline was 233 mg/dL (range of 129 to 399). The 12-week double-blind phase was followed by a 40 week open-label dose-titration phase, where all patients (n=173) received 5 mg, 10 mg or 20 mg rosuvastatin daily." }

Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Results are shown in Table 13 below.

{ "type": "p", "children": [], "text": "Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Results are shown in Table 13 below." }

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 13: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 10 to 17 years of Age with HeFH (Least-Squares Mean Percent Change from Baseline To Week 12)</span> </caption> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule">Dose (mg)</th><th align="center" class="Botrule Rrule">N</th><th align="center" class="Botrule Rrule">LDL-C</th><th align="center" class="Botrule Rrule" scope="row">HDL-C</th><th align="center" class="Botrule Rrule">Total-C</th><th align="center" class="Botrule Rrule">TG <span class="Sup">1</span></th><th align="center" class="Botrule Rrule">ApoB</th> </tr> </thead> <tfoot> <tr class="First"> <td align="left" colspan="7"><span class="Sup">1</span>Median percent change </td> </tr> <tr class="Last"> <td align="left" colspan="7"><span class="Sup">2</span>Difference from placebo not statistically significant </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center" class="Botrule Lrule Rrule">Placebo</td><td align="center" class="Botrule Rrule">46</td><td align="center" class="Botrule Rrule">-1%</td><td align="center" class="Botrule Rrule">+7%</td><td align="center" class="Botrule Rrule">0%</td><td align="center" class="Botrule Rrule">-7%</td><td align="center" class="Botrule Rrule">-2%</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5</td><td align="center" class="Botrule Rrule">42</td><td align="center" class="Botrule Rrule">-38%</td><td align="center" class="Botrule Rrule">+4% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-30%</td><td align="center" class="Botrule Rrule">-13% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-32%</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10</td><td align="center" class="Botrule Rrule">44</td><td align="center" class="Botrule Rrule">-45%</td><td align="center" class="Botrule Rrule">+11% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-34%</td><td align="center" class="Botrule Rrule">-15% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-38%</td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule">20</td><td align="center" class="Botrule Rrule">44</td><td align="center" class="Botrule Rrule">-50%</td><td align="center" class="Botrule Rrule">+9% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-39%</td><td align="center" class="Botrule Rrule">16% <span class="Sup">2</span></td><td align="center" class="Botrule Rrule">-41%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<caption>\n<span>Table 13: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 10 to 17 years of Age with HeFH (Least-Squares Mean Percent Change from Baseline To Week 12)</span>\n</caption>\n<col align=\"center\" valign=\"top\" width=\"15%\"/>\n<col align=\"center\" valign=\"top\" width=\"14%\"/>\n<col align=\"center\" valign=\"top\" width=\"14%\"/>\n<col align=\"center\" valign=\"top\" width=\"14%\"/>\n<col align=\"center\" valign=\"top\" width=\"15%\"/>\n<col align=\"center\" valign=\"top\" width=\"14%\"/>\n<col align=\"center\" valign=\"top\" width=\"14%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Botrule Lrule Rrule\">Dose (mg)</th><th align=\"center\" class=\"Botrule Rrule\">N</th><th align=\"center\" class=\"Botrule Rrule\">LDL-C</th><th align=\"center\" class=\"Botrule Rrule\" scope=\"row\">HDL-C</th><th align=\"center\" class=\"Botrule Rrule\">Total-C</th><th align=\"center\" class=\"Botrule Rrule\">TG\n \n <span class=\"Sup\">1</span></th><th align=\"center\" class=\"Botrule Rrule\">ApoB</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"7\"><span class=\"Sup\">1</span>Median percent change\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"7\"><span class=\"Sup\">2</span>Difference from placebo not statistically significant\n \n </td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule\">Placebo</td><td align=\"center\" class=\"Botrule Rrule\">46</td><td align=\"center\" class=\"Botrule Rrule\">-1%</td><td align=\"center\" class=\"Botrule Rrule\">+7%</td><td align=\"center\" class=\"Botrule Rrule\">0%</td><td align=\"center\" class=\"Botrule Rrule\">-7%</td><td align=\"center\" class=\"Botrule Rrule\">-2%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\">5</td><td align=\"center\" class=\"Botrule Rrule\">42</td><td align=\"center\" class=\"Botrule Rrule\">-38%</td><td align=\"center\" class=\"Botrule Rrule\">+4%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-30%</td><td align=\"center\" class=\"Botrule Rrule\">-13%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-32%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\">10</td><td align=\"center\" class=\"Botrule Rrule\">44</td><td align=\"center\" class=\"Botrule Rrule\">-45%</td><td align=\"center\" class=\"Botrule Rrule\">+11%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-34%</td><td align=\"center\" class=\"Botrule Rrule\">-15%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-38%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule\">20</td><td align=\"center\" class=\"Botrule Rrule\">44</td><td align=\"center\" class=\"Botrule Rrule\">-50%</td><td align=\"center\" class=\"Botrule Rrule\">+9%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-39%</td><td align=\"center\" class=\"Botrule Rrule\">16%\n \n <span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Rrule\">-41%</td>\n</tr>\n</tbody>\n</table></div>" }

Rosuvastatin was also studied in a two-year open-label, uncontrolled, titration-to-goal trial that included 175 pediatric patients with HeFH who were 8 to 17 years old (79 males and 96 females). All patients had a documented genetic defect in the LDL receptor or in ApoB. Approximately 89% were White, 7% were Asian, 1% were Black or African American, and fewer than 1% were Hispanic or Latino ethnicity. Mean LDL-C at baseline was 236 mg/dL. Fifty-eight (33%) patients were prepubertal at baseline. The starting rosuvastatin dosage for all pediatric patients was 5 mg once daily. Pediatric patients aged 8 to less than 10 years (n=41 at baseline) could titrate to a maximum dosage of 10 mg once daily, and pediatric patients aged 10 to 17 years could titrate to a maximum dosage of 20 mg once daily.

{ "type": "p", "children": [], "text": "Rosuvastatin was also studied in a two-year open-label, uncontrolled, titration-to-goal trial that included 175 pediatric patients with HeFH who were 8 to 17 years old (79 males and 96 females). All patients had a documented genetic defect in the LDL receptor or in ApoB. Approximately 89% were White, 7% were Asian, 1% were Black or African American, and fewer than 1% were Hispanic or Latino ethnicity. Mean LDL-C at baseline was 236 mg/dL. Fifty-eight (33%) patients were prepubertal at baseline. The starting rosuvastatin dosage for all pediatric patients was 5 mg once daily. Pediatric patients aged 8 to less than 10 years (n=41 at baseline) could titrate to a maximum dosage of 10 mg once daily, and pediatric patients aged 10 to 17 years could titrate to a maximum dosage of 20 mg once daily." }

The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous experience in both adult and pediatric controlled trials.

{ "type": "p", "children": [], "text": "The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous experience in both adult and pediatric controlled trials." }

HoFH in Adult and Pediatric Patients

{ "type": "p", "children": [], "text": "\nHoFH in Adult and Pediatric Patients\n" }

In an open-label, forced-titration study, HoFH patients (n=40, 8 years 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-C 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.

{ "type": "p", "children": [], "text": "In an open-label, forced-titration study, HoFH patients (n=40, 8 years 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-C 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." }

HoFH in Pediatric Patients

{ "type": "p", "children": [], "text": "\nHoFH in Pediatric Patients\n" }

Rosuvastatin was studied in a randomized, double-blind, placebo-controlled, multicenter, cross-over study in 14 pediatric patients with HoFH. The study included a 4-week dietary lead-in phase during which patients received rosuvastatin 10 mg daily, a cross-over phase that included two 6-week treatment periods with either rosuvastatin 20 mg or placebo in random order, followed by a 12-week open-label phase during which all patients received rosuvastatin 20 mg. Patients ranged in age from 7 to 15 years of age (median 11 years), 50% were male, 71% were White, 21% were Asian, 7% were Black or African American, and no patients were of Hispanic or Latino ethnicity. Fifty percent were on apheresis therapy and 57% were taking ezetimibe. Patients who entered the study on apheresis therapy or ezetimibe continued the treatment throughout the entire study. Mean LDL-C at baseline was 416 mg/dL (range 152 mg/dL to 716 mg/dL). A total of 13 patients completed both treatment periods of the randomized cross-over phase; one patient withdrew consent due to inability to have blood drawn during the cross-over phase.

{ "type": "p", "children": [], "text": "Rosuvastatin was studied in a randomized, double-blind, placebo-controlled, multicenter, cross-over study in 14 pediatric patients with HoFH. The study included a 4-week dietary lead-in phase during which patients received rosuvastatin 10 mg daily, a cross-over phase that included two 6-week treatment periods with either rosuvastatin 20 mg or placebo in random order, followed by a 12-week open-label phase during which all patients received rosuvastatin 20 mg. Patients ranged in age from 7 to 15 years of age (median 11 years), 50% were male, 71% were White, 21% were Asian, 7% were Black or African American, and no patients were of Hispanic or Latino ethnicity. Fifty percent were on apheresis therapy and 57% were taking ezetimibe. Patients who entered the study on apheresis therapy or ezetimibe continued the treatment throughout the entire study. Mean LDL-C at baseline was 416 mg/dL (range 152 mg/dL to 716 mg/dL). A total of 13 patients completed both treatment periods of the randomized cross-over phase; one patient withdrew consent due to inability to have blood drawn during the cross-over phase." }

Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo (Table 14).

{ "type": "p", "children": [], "text": "Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo (Table 14)." }

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 14: Lipid-modifying Effects of Rosuvastatin in Pediatric Patients 7 to 15 years of Age with HoFH After 6 Weeks</span> </caption> <col align="left" valign="top" width="25%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="30%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule"></th><th align="center" class="Botrule Rrule">Placebo <br/> (N=13) </th><th align="center" class="Botrule Rrule">Rosuvastatin 20 mg <br/> (N=13) </th><th align="center" class="Botrule Rrule">Percent difference (95% CI)</th> </tr> </thead> <tfoot> <tr class="First"> <td align="left" colspan="4">% Difference estimates are based on transformations of the estimated mean difference in log LDL measurements between rosuvastatin and placebo using a mixed model adjusted for study period</td> </tr> <tr> <td align="left" colspan="4"><span class="Sup">1</span>p=0.005, </td> </tr> <tr> <td align="left" colspan="4"><span class="Sup">2</span>p=0.003, </td> </tr> <tr class="Last"> <td align="left" colspan="4"><span class="Sup">3</span>p=0.024, </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule">LDL-C (mg/dL)</td><td align="center" class="Botrule Rrule">481</td><td align="center" class="Botrule Rrule">396</td><td align="center" class="Botrule Rrule">-22.3% (-33.5, -9.1) <span class="Sup">1</span></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Total-C (mg/dL)</td><td align="center" class="Botrule Rrule">539</td><td align="center" class="Botrule Rrule">448</td><td align="center" class="Botrule Rrule">-20.1% (-29.7, -9.1) <span class="Sup">2</span></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Non-HDL-C (mg/dL)</td><td align="center" class="Botrule Rrule">505</td><td align="center" class="Botrule Rrule">412</td><td align="center" class="Botrule Rrule">-22.9% (-33.7, -10.3) <span class="Sup">2</span></td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">ApoB (mg/dL)</td><td align="center" class="Botrule Rrule">268</td><td align="center" class="Botrule Rrule">235</td><td align="center" class="Botrule Rrule">-17.1% (-29.2, -2.9) <span class="Sup">3</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<caption>\n<span>Table 14: Lipid-modifying Effects of Rosuvastatin in Pediatric Patients 7 to 15 years of Age with HoFH After 6 Weeks</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"30%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule\"></th><th align=\"center\" class=\"Botrule Rrule\">Placebo \n <br/> (N=13)\n </th><th align=\"center\" class=\"Botrule Rrule\">Rosuvastatin 20 mg \n <br/> (N=13)\n </th><th align=\"center\" class=\"Botrule Rrule\">Percent difference (95% CI)</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"4\">% Difference estimates are based on transformations of the estimated mean difference in log LDL measurements between rosuvastatin and placebo using a mixed model adjusted for study period</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"4\"><span class=\"Sup\">1</span>p=0.005,\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"4\"><span class=\"Sup\">2</span>p=0.003,\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"4\"><span class=\"Sup\">3</span>p=0.024,\n \n </td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">LDL-C (mg/dL)</td><td align=\"center\" class=\"Botrule Rrule\">481</td><td align=\"center\" class=\"Botrule Rrule\">396</td><td align=\"center\" class=\"Botrule Rrule\">-22.3% (-33.5, -9.1)\n \n <span class=\"Sup\">1</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Total-C (mg/dL)</td><td align=\"center\" class=\"Botrule Rrule\">539</td><td align=\"center\" class=\"Botrule Rrule\">448</td><td align=\"center\" class=\"Botrule Rrule\">-20.1% (-29.7, -9.1)\n \n <span class=\"Sup\">2</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Non-HDL-C (mg/dL)</td><td align=\"center\" class=\"Botrule Rrule\">505</td><td align=\"center\" class=\"Botrule Rrule\">412</td><td align=\"center\" class=\"Botrule Rrule\">-22.9% (-33.7, -10.3)\n \n <span class=\"Sup\">2</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">ApoB (mg/dL)</td><td align=\"center\" class=\"Botrule Rrule\">268</td><td align=\"center\" class=\"Botrule Rrule\">235</td><td align=\"center\" class=\"Botrule Rrule\">-17.1% (-29.2, -2.9)\n \n <span class=\"Sup\">3</span></td>\n</tr>\n</tbody>\n</table></div>" }

Primary Dysbetalipoproteinemia in Adults

{ "type": "p", "children": [], "text": "\nPrimary Dysbetalipoproteinemia in Adults\n" }

In a randomized, multicenter, double-blind crossover study, 32 adult patients (27 with є2/є2 and 4 with apo E mutation [Arg145Cys] with primary dysbetalipoproteinemia 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 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.

{ "type": "p", "children": [], "text": "In a randomized, multicenter, double-blind crossover study, 32 adult patients (27 with є2/є2 and 4 with apo E mutation [Arg145Cys] with primary dysbetalipoproteinemia 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 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." }

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 15: Lipid-modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32)</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="30%"/> <tbody class="Headless"> <tr class="First"> <th align="left" class="Botrule Lrule Rrule"></th><th align="left" class="Botrule Rrule">Median at Baseline (mg/dL)</th><th align="left" class="Botrule Rrule">Median percent change from baseline (95% CI) Rosuvastatin 10 mg</th><th align="left" class="Botrule Rrule">Median percent change from baseline (95% CI) Rosuvastatin 20 mg</th> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Total-C</td><td align="left" class="Botrule Rrule">342.5</td><td align="left" class="Botrule Rrule">-43.3 <br/> (-46.9, -37.5) </td><td align="left" class="Botrule Rrule">-47.6 <br/> (-51.6, -42.8) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Triglycerides</td><td align="left" class="Botrule Rrule">503.5</td><td align="left" class="Botrule Rrule">-40.1 <br/> (-44.9, -33.6) </td><td align="left" class="Botrule Rrule">-43.0 <br/> (-52.5, -33.1) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Non-HDL-C</td><td align="left" class="Botrule Rrule">294.5</td><td align="left" class="Botrule Rrule">-48.2 <br/> (-56.7, -45.6) </td><td align="left" class="Botrule Rrule">-56.4 <br/> (-61.4, -48.5) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">VLDL-C + IDL-C</td><td align="left" class="Botrule Rrule">209.5</td><td align="left" class="Botrule Rrule">-46.8 <br/> (-53.7, -39.4) </td><td align="left" class="Botrule Rrule">-56.2 <br/> (-67.7, -43.7) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">LDL-C</td><td align="left" class="Botrule Rrule">112.5</td><td align="left" class="Botrule Rrule">-54.4 <br/> (-59.1, -47.3) </td><td align="left" class="Botrule Rrule">-57.3 <br/> (-59.4, -52.1) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">HDL-C</td><td align="left" class="Botrule Rrule">35.5</td><td align="left" class="Botrule Rrule">10.2 <br/> (1.9, 12.3) </td><td align="left" class="Botrule Rrule">11.2 <br/> (8.3, 20.5) </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">RLP-C</td><td align="left" class="Botrule Rrule">82.0</td><td align="left" class="Botrule Rrule">-56.4 <br/> (-67.1, -49.0) </td><td align="left" class="Botrule Rrule">-64.9 <br/> (-74.0, -56.6) </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">Apo-E</td><td align="left" class="Botrule Rrule">16.0</td><td align="left" class="Botrule Rrule">-42.9 <br/> (-46.3, -33.3) </td><td align="left" class="Botrule Rrule">-42.5 <br/> (-47.1, -35.6) </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<caption>\n<span>Table 15: Lipid-modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32)</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<th align=\"left\" class=\"Botrule Lrule Rrule\"></th><th align=\"left\" class=\"Botrule Rrule\">Median at Baseline (mg/dL)</th><th align=\"left\" class=\"Botrule Rrule\">Median percent change from baseline (95% CI) Rosuvastatin 10 mg</th><th align=\"left\" class=\"Botrule Rrule\">Median percent change from baseline (95% CI) Rosuvastatin 20 mg</th>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Total-C</td><td align=\"left\" class=\"Botrule Rrule\">342.5</td><td align=\"left\" class=\"Botrule Rrule\">-43.3 \n <br/> (-46.9, -37.5)\n </td><td align=\"left\" class=\"Botrule Rrule\">-47.6 \n <br/> (-51.6, -42.8)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Triglycerides</td><td align=\"left\" class=\"Botrule Rrule\">503.5</td><td align=\"left\" class=\"Botrule Rrule\">-40.1 \n <br/> (-44.9, -33.6)\n </td><td align=\"left\" class=\"Botrule Rrule\">-43.0 \n <br/> (-52.5, -33.1)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Non-HDL-C</td><td align=\"left\" class=\"Botrule Rrule\">294.5</td><td align=\"left\" class=\"Botrule Rrule\">-48.2 \n <br/> (-56.7, -45.6)\n </td><td align=\"left\" class=\"Botrule Rrule\">-56.4 \n <br/> (-61.4, -48.5)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">VLDL-C + IDL-C</td><td align=\"left\" class=\"Botrule Rrule\">209.5</td><td align=\"left\" class=\"Botrule Rrule\">-46.8 \n <br/> (-53.7, -39.4)\n </td><td align=\"left\" class=\"Botrule Rrule\">-56.2 \n <br/> (-67.7, -43.7)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">LDL-C</td><td align=\"left\" class=\"Botrule Rrule\">112.5</td><td align=\"left\" class=\"Botrule Rrule\">-54.4 \n <br/> (-59.1, -47.3)\n </td><td align=\"left\" class=\"Botrule Rrule\">-57.3 \n <br/> (-59.4, -52.1)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">HDL-C</td><td align=\"left\" class=\"Botrule Rrule\">35.5</td><td align=\"left\" class=\"Botrule Rrule\">10.2 \n <br/> (1.9, 12.3)\n </td><td align=\"left\" class=\"Botrule Rrule\">11.2 \n <br/> (8.3, 20.5)\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">RLP-C</td><td align=\"left\" class=\"Botrule Rrule\">82.0</td><td align=\"left\" class=\"Botrule Rrule\">-56.4 \n <br/> (-67.1, -49.0)\n </td><td align=\"left\" class=\"Botrule Rrule\">-64.9 \n <br/> (-74.0, -56.6)\n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Apo-E</td><td align=\"left\" class=\"Botrule Rrule\">16.0</td><td align=\"left\" class=\"Botrule Rrule\">-42.9 \n <br/> (-46.3, -33.3)\n </td><td align=\"left\" class=\"Botrule Rrule\">-42.5 \n <br/> (-47.1, -35.6)\n </td>\n</tr>\n</tbody>\n</table></div>" }

Hypertriglyceridemia in Adults

{ "type": "p", "children": [], "text": "\nHypertriglyceridemia in Adults\n" }

In a double-blind, placebo-controlled study in adult patients with baseline TG levels from 273 mg/dL 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 16).

{ "type": "p", "children": [], "text": "In a double-blind, placebo-controlled study in adult patients with baseline TG levels from 273 mg/dL 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 16)." }

<div class="scrollingtable"><table width="70%"> <caption> <span>Table 16: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Primary Hypertriglyceridemia After Six Weeks by Median (Min, Max) Percent Change from Baseline to Week 6</span> </caption> <col align="left" valign="top" width="10%"/> <col align="left" valign="top" width="10%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule">Dose</th><th align="left" class="Botrule Rrule">Placebo (n=26)</th><th align="left" class="Botrule Rrule">Rosuvastatin 5 mg (n=25)</th><th align="left" class="Botrule Rrule">Rosuvastatin 10 mg (n=23)</th><th align="left" class="Botrule Rrule">Rosuvastatin 20 mg (n=27)</th><th align="left" class="Botrule Rrule">Rosuvastatin 40 mg (n=25)</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule">Triglycerides</td><td align="left" class="Botrule Rrule">1 (-40, 72)</td><td align="left" class="Botrule Rrule">-21 (-58, 38)</td><td align="left" class="Botrule Rrule">-37 (-65, 5)</td><td align="left" class="Botrule Rrule">-37 (-72, 11)</td><td align="left" class="Botrule Rrule">-43 (-80, -7)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Non-HDL-C</td><td align="left" class="Botrule Rrule">2 (-13, 19)</td><td align="left" class="Botrule Rrule">-29 (-43, -8)</td><td align="left" class="Botrule Rrule">-49 (-59, -20)</td><td align="left" class="Botrule Rrule">-43 (-74, 12)</td><td align="left" class="Botrule Rrule">-51 (-62, -6)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Total-C</td><td align="left" class="Botrule Rrule">1 (-13, 17)</td><td align="left" class="Botrule Rrule">-24 (-40, -4)</td><td align="left" class="Botrule Rrule">-40 (-51, -14)</td><td align="left" class="Botrule Rrule">-34 (-61, -11)</td><td align="left" class="Botrule Rrule">-40 (-51, -4)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">LDL-C</td><td align="left" class="Botrule Rrule">5 (-30, 52)</td><td align="left" class="Botrule Rrule">-28 (-71, 2)</td><td align="left" class="Botrule Rrule">-45 (-59, 7)</td><td align="left" class="Botrule Rrule">-31 (-66, 34)</td><td align="left" class="Botrule Rrule">-43 (-61, -3)</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">HDL-C</td><td align="left" class="Botrule Rrule">-3 (-25, 18)</td><td align="left" class="Botrule Rrule">3 (-38, 33)</td><td align="left" class="Botrule Rrule">8 (-8, 24)</td><td align="left" class="Botrule Rrule">22 (-5, 50)</td><td align="left" class="Botrule Rrule">17 (-14, 63)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"70%\">\n<caption>\n<span>Table 16: Lipid-Modifying Effect of Rosuvastatin in Adult Patients with Primary Hypertriglyceridemia After Six Weeks by Median (Min, Max) Percent Change from Baseline to Week 6</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"10%\"/>\n<col align=\"left\" valign=\"top\" width=\"10%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule\">Dose</th><th align=\"left\" class=\"Botrule Rrule\">Placebo (n=26)</th><th align=\"left\" class=\"Botrule Rrule\">Rosuvastatin 5 mg (n=25)</th><th align=\"left\" class=\"Botrule Rrule\">Rosuvastatin 10 mg (n=23)</th><th align=\"left\" class=\"Botrule Rrule\">Rosuvastatin 20 mg (n=27)</th><th align=\"left\" class=\"Botrule Rrule\">Rosuvastatin 40 mg (n=25)</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Triglycerides</td><td align=\"left\" class=\"Botrule Rrule\">1 (-40, 72)</td><td align=\"left\" class=\"Botrule Rrule\">-21 (-58, 38)</td><td align=\"left\" class=\"Botrule Rrule\">-37 (-65, 5)</td><td align=\"left\" class=\"Botrule Rrule\">-37 (-72, 11)</td><td align=\"left\" class=\"Botrule Rrule\">-43 (-80, -7)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Non-HDL-C</td><td align=\"left\" class=\"Botrule Rrule\">2 (-13, 19)</td><td align=\"left\" class=\"Botrule Rrule\">-29 (-43, -8)</td><td align=\"left\" class=\"Botrule Rrule\">-49 (-59, -20)</td><td align=\"left\" class=\"Botrule Rrule\">-43 (-74, 12)</td><td align=\"left\" class=\"Botrule Rrule\">-51 (-62, -6)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Total-C</td><td align=\"left\" class=\"Botrule Rrule\">1 (-13, 17)</td><td align=\"left\" class=\"Botrule Rrule\">-24 (-40, -4)</td><td align=\"left\" class=\"Botrule Rrule\">-40 (-51, -14)</td><td align=\"left\" class=\"Botrule Rrule\">-34 (-61, -11)</td><td align=\"left\" class=\"Botrule Rrule\">-40 (-51, -4)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">LDL-C</td><td align=\"left\" class=\"Botrule Rrule\">5 (-30, 52)</td><td align=\"left\" class=\"Botrule Rrule\">-28 (-71, 2)</td><td align=\"left\" class=\"Botrule Rrule\">-45 (-59, 7)</td><td align=\"left\" class=\"Botrule Rrule\">-31 (-66, 34)</td><td align=\"left\" class=\"Botrule Rrule\">-43 (-61, -3)</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">HDL-C</td><td align=\"left\" class=\"Botrule Rrule\">-3 (-25, 18)</td><td align=\"left\" class=\"Botrule Rrule\">3 (-38, 33)</td><td align=\"left\" class=\"Botrule Rrule\">8 (-8, 24)</td><td align=\"left\" class=\"Botrule Rrule\">22 (-5, 50)</td><td align=\"left\" class=\"Botrule Rrule\">17 (-14, 63)</td>\n</tr>\n</tbody>\n</table></div>" }

Rosuvastatin tablets, USP are supplied as: 20 mg, Pink colored, round, biconvex, film coated tablets, debossed with SG on one side and 118 other side

{ "type": "p", "children": [], "text": "Rosuvastatin tablets, USP are supplied as:\n \n20 mg, Pink colored, round, biconvex, film coated tablets, debossed with SG on one side and 118 other side\n " }

NDC: 70518-4296-00 NDC: 70518-4296-01 NDC: 70518-4296-02

{ "type": "p", "children": [], "text": "\n\nNDC: 70518-4296-00\n \nNDC: 70518-4296-01\n \nNDC: 70518-4296-02\n " }

NDC: 70518-4296-03 PACKAGING: 45 in 1 BOTTLE PLASTIC PACKAGING: 100 in 1 BOTTLE PLASTIC PACKAGING: 90 in 1 BOTTLE PLASTIC

{ "type": "p", "children": [], "text": "NDC: 70518-4296-03\n \nPACKAGING: 45 in 1 BOTTLE PLASTIC\n \nPACKAGING: 100 in 1 BOTTLE PLASTIC\n \nPACKAGING: 90 in 1 BOTTLE PLASTIC\n " }

PACKAGING: 30 in 1 BLISTER PACK

{ "type": "p", "children": [], "text": "PACKAGING: 30 in 1 BLISTER PACK" }

Storage

{ "type": "p", "children": [], "text": "Storage" }

Store at controlled room temperature, 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

{ "type": "p", "children": [], "text": "Store at controlled room temperature, 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture." }

Repackaged and Distributed By:

{ "type": "p", "children": [], "text": "Repackaged and Distributed By:" }

Remedy Repack, Inc.

{ "type": "p", "children": [], "text": "Remedy Repack, Inc." }

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

{ "type": "p", "children": [], "text": "625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762" }

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

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling ( \n Patient Information).\n " }

Myopathy and Rhabdomyolysis

{ "type": "p", "children": [], "text": "\nMyopathy and Rhabdomyolysis\n" }

Advise patients that rosuvastatin may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over-the-counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.1), and Drug Interactions (7.1)].

{ "type": "p", "children": [], "text": "Advise patients that rosuvastatin may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over-the-counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever \n [see \n Warnings and Precautions (5.1), and \n Drug Interactions (7.1)]. \n \n" }

Hepatic Dysfunction

{ "type": "p", "children": [], "text": "\nHepatic Dysfunction\n" }

Inform patients that rosuvastatin may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.3)] .

{ "type": "p", "children": [], "text": "Inform patients that rosuvastatin may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice \n [see \n Warnings and Precautions (5.3)] \n .\n " }

Increases in HbA1c and Fasting Serum Glucose Levels

{ "type": "p", "children": [], "text": "\nIncreases in HbA1c and Fasting Serum Glucose Levels\n" }

Inform patients that increases in HbA1c and fasting serum glucose levels may occur with rosuvastatin. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions (5.5)] .

{ "type": "p", "children": [], "text": "Inform patients that increases in HbA1c and fasting serum glucose levels may occur with rosuvastatin. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices \n [see \n Warnings and Precautions (5.5)] \n .\n " }

Pregnancy

{ "type": "p", "children": [], "text": "\nPregnancy\n" }

Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if rosuvastatin should be discontinued [see Use in Specific Populations (8.1)] .

{ "type": "p", "children": [], "text": "Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if rosuvastatin should be discontinued \n [see \n Use in Specific Populations (8.1)] \n .\n " }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise patients that breastfeeding during treatment with rosuvastatin is not recommended [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise patients that breastfeeding during treatment with rosuvastatin is not recommended \n [see \n Use in Specific Populations (8.2)]. \n \n" }

Concomitant Use of Antacids

{ "type": "p", "children": [], "text": "\nConcomitant Use of Antacids\n" }

When taking rosuvastatin with an aluminum and magnesium hydroxide combination antacid, administer rosuvastatin tablets at least 2 hours before the antacid [see Drug Interactions (7.2)] .

{ "type": "p", "children": [], "text": "When taking rosuvastatin with an aluminum and magnesium hydroxide combination antacid, administer rosuvastatin tablets at least 2 hours before the antacid \n [see \n Drug Interactions (7.2)] \n .\n " }

Missed Doses

{ "type": "p", "children": [], "text": "\nMissed Doses\n" }

If a dose is missed, advise patients no to take an extra dose. Just resume the usual schedule [see Dosage and Administration (2.1)] .

{ "type": "p", "children": [], "text": "If a dose is missed, advise patients no to take an extra dose. Just resume the usual schedule \n [see \n Dosage and Administration (2.1)] \n .\n " }

Repackaged By / Distributed By: RemedyRepack Inc.

{ "type": "p", "children": [], "text": "Repackaged By / Distributed By: RemedyRepack Inc." }

625 Kolter Drive, Indiana, PA 15701

{ "type": "p", "children": [], "text": "625 Kolter Drive, Indiana, PA 15701" }

(724) 465-8762

{ "type": "p", "children": [], "text": "(724) 465-8762" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="6%"/> <col align="left" valign="top" width="44%"/> <col align="left" valign="top" width="40%"/> <col align="left" valign="top" width="10%"/> <tfoot> <tr class="First First Last Last"> <td align="left" colspan="3">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align="right" colspan="1">Rev:8/2024</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First First"> <td align="center" class="Lrule Rrule" colspan="4"><span class="Bold">PATIENT INFORMATION</span> <br/> Rosuvastatin Tablets, USP for oral use <br/> (roe-SOO-va-STAT-in) </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Read this Patient Information carefully before you start taking rosuvastatin tablets and each time you get a refill. If you have any questions about rosuvastatin tablets, ask your healthcare provider. Only your healthcare provider can determine if rosuvastatin tablets are right for you.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are rosuvastatin tablets?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Rosuvastatin tablets are prescription medicine that contains a cholesterol-lowering medicine called rosuvastatin calcium.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li>Rosuvastatin tablets are used: <ul class="Circle"> <li>to reduce the risk of major adverse cardiovascular (CV) events, such as death from cardiovascular disease, heart attack, stroke, or the need for procedures to improve blood flow to the heart called arterial revascularization, in adults who do not have known heart disease but do have certain additional risk factors.</li> <li>along with diet to: <ul class="Circle"> <li>lower the level of low-density lipoprotein (LDL-C) cholesterol or “bad” cholesterol in adults with primary hyperlipidemia.</li> <li>slow the buildup of fatty deposits (plaque) in the walls of blood vessels.</li> <li>treat adults and children 8 years of age and older with high blood cholesterol due to heterozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).</li> </ul> </li> </ul> <ul class="Circle"> <li>along with other cholesterol lowering treatments or alone if such treatments are unavailable in adults and children 7 years of age and older with homozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).</li> <li>along with diet for the treatment of adults with: <ul class="Circle"> <li>primary dysbetalipoproteinemia (an inherited condition that causes high levels of cholesterol and fat).</li> <li>hypertriglyceridemia.</li> </ul> </li> </ul> </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">It is not known if rosuvastatin tablets are safe and effective in children younger than 8 years of age with HeFH or children younger than 7 years of age with HoFH or in children with other types of hyperlipidemias (other than HeFH or HoFH).</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Do not take rosuvastatin tablets if you:</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li>have liver problems.</li> <li>are allergic to rosuvastatin or any of the ingredients in rosuvastatin tablets. See the end of this leaflet for a complete list of ingredients in rosuvastatin tablets. Symptoms of allergic reactions include rash, itching, hives, and swelling.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Before you take rosuvastatin tablets, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have unexplained muscle aches or weakness.</li> <li>have or have had kidney problems.</li> <li>have or have had liver problems.</li> <li>drink more than 2 glasses of alcohol daily.</li> <li>have thyroid problems.</li> <li>are of Asian descent.</li> <li>are pregnant or think you may be pregnant, or are planning to become pregnant. If you become pregnant while taking rosuvastatin tablets, call your healthcare provider right away to discuss your rosuvastatin tablets treatment.</li> <li>are breastfeeding. rosuvastatin can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take rosuvastatin tablets. Do not breastfeed while taking rosuvastatin tablets.</li> </ul> <p class="First"> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider who prescribes rosuvastatin tablets if another healthcare provider increases the dose of another medicine you are taking. </p> <p>Rosuvastatin tablets may affect the way other medicines work, and other medicines may affect how rosuvastatin tablets works.</p> <p> <a name="Esp"></a>Especially tell your healthcare provider if you take:</p> <ul class="Disc"> <li>coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)</li> <li>antacids (medicines you take for heartburn that contain aluminium and magnesium hydroxide)</li> </ul> <p>Taking rosuvastatin tablets with certain medicines may increase the risk of muscle problems.</p> <p>Especially tell your healthcare provider if you take:</p> <ul class="Disc"> <li>cyclosporine (a medicine for your immune system)</li> <li>teriflunomide (a medicine used to treat relapsing remitting multiple sclerosis)</li> <li>enasidenib (a medicine used to treat acute myeloid leukemia)</li> <li>capmatinib (a medicine for the treatment of non-small cell lung cancer)</li> <li>fostamatinib (a medicine used to treat low platelet counts)</li> <li>febuxostat (a medicine used to treat and prevent high blood levels of uric acid)</li> <li>gemfibrozil (a fibric acid medicine for lowering cholesterol)</li> <li>tafamidis (used to treat cardiomyopathy [enlarged and thickened heart muscle])</li> <li>anti-viral medicines including certain HIV or hepatitis C virus drugs such as: <ul class="Circle"> <li>lopinavir, ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir</li> <li>combination of <ul class="Disc"> <li>sofosbuvir/velpatasvir/voxilaprevir</li> <li>dasabuvir/ombitasvir/paritaprevir/ritonavir</li> <li>elbasvir/grazoprevir</li> <li>sofosbuvir/velpatasvir</li> <li>glecaprevir/pibrentasvir and</li> </ul> </li> <li>all other combinations with ledipasvir including ledipasvir/sofosbuvir</li> </ul> </li> <li>darolutamide (a medicine for the treatment of prostate cancer)</li> <li>regorafenib (a medicine used to treat cancer of the colon and rectum)</li> <li>fibric acid derivatives (such as fenofibrate)</li> <li>ticagrelor (helps reduce the chance of a blood clot formation that can block a blood vessel)</li> <li>niacin or nicotinic acid</li> <li>colchicine (a medicine used to treat gout)</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get new medicine.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I take rosuvastatin tablets?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li>Take rosuvastatin tablets exactly as your healthcare provider tells you to take it.</li> <li>Take rosuvastatin tablets, by mouth, 1 time each day. Swallow the tablet whole.</li> <li>Rosuvastatin tablets can be taken at any time of day, with or without food.</li> <li> <span class="Bold">Do not</span>change your dose or stop rosuvastatin tablets without talking to your healthcare provider, even if you are feeling well. </li> <li>Your healthcare provider may do blood tests to check your cholesterol levels before and during your treatment with rosuvastatin tablets. Your healthcare provider may change your dose of rosuvastatin tablets if needed.</li> <li>While taking rosuvastatin tablets, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.</li> <li>If you take a medicine called an antacid that contains a combination of aluminum and magnesium hydroxide, take rosuvastatin tablets at least 2 hours before you take the antacid.</li> <li>If you miss a dose of rosuvastatin tablets, take your next dose at your normal scheduled time. <span class="Bold">Do not take</span>an extra dose of rosuvastatin tablets. </li> <li>In case of an overdose, get medical help or contact a live Poison Center expert right away at 1-800-222-1222. Advice is also available online at <a href="http://poisonhelp.org">poisonhelp.org</a>. </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the possible side effects of rosuvastatin tablets? <br/> Rosuvastatin tablets may cause serious side effects, including: </span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">Muscle pain, tenderness and weakness (myopathy).</span>Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death. Tell your healthcare provider right away if: <ul class="Circle"> <li>you have unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel more tired than usual, while you take rosuvastatin tablets.</li> <li>you have muscle problems that do not go away even after your healthcare provider has told you to stop taking rosuvastatin tablets. Your healthcare provider may do further tests to diagnose the cause of your muscle problems. <br/> Your chances of getting muscle problems are higher if you: </li> <li>are taking certain other medicines while you take rosuvastatin tablets (see <a href="#Esp">“Especially tell your healthcare provider if you take”</a>) </li> <li>are 65 years of age or older</li> <li>are of Asian descent</li> <li>have thyroid problems (hypothyroidism) that are not controlled</li> <li>have kidney problems</li> <li>are taking higher doses of rosuvastatin tablets</li> </ul> </li> <li> <span class="Bold">Liver problems.</span>Your healthcare provider may do blood tests to check your liver before you start taking rosuvastatin tablets and if you have symptoms of liver problems while you take rosuvastatin tablets. Call your healthcare provider right away if you have any of the following symptoms of liver problems: <ul class="Circle"> <li>feel unusually tired or weak</li> <li>loss of appetite</li> <li>upper belly pain</li> <li>dark urine</li> <li>yellowing of your skin or the whites of your eyes</li> </ul> </li> <li> <span class="Bold">Protein and blood in the urine.</span>Rosuvastatin tablets may cause you to have protein and blood in your urine. If you develop protein or blood in your urine, your healthcare provider may decrease your dose of rosuvastatin tablets. </li> <li> <span class="Bold">Increase in blood sugar (glucose) levels.</span>Rosuvastatin tablets may cause an increase in your blood sugar levels. </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">The most common side effects may include headache, nausea, muscle aches and pains, weakness, and constipation.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">For more information, ask your healthcare provider or pharmacist.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I store rosuvastatin tablets?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li>Store rosuvastatin tablets at room temperature, between 68°F to 77°F (20°C to 25°C) and in a dry place.</li> </ul> <p class="First"> <span class="Bold">Keep rosuvastatin tablets and all medicines out of the reach of children.</span> </p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">General Information about the safe and effective use of rosuvastatin tablets</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use rosuvastatin tablets for a condition for which it was not prescribed. Do not give rosuvastatin tablets to other people, even if they have the same medical condition you have. It may harm them. <br/> You can ask your pharmacist or healthcare provider for information about rosuvastatin tablets that is written for health professionals. </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the Ingredients in Rosuvastatin Tablets, USP?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Active ingredient:</span>rosuvastatin as rosuvastatin calcium, USP (amorphous) </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Inactive ingredients:</span>crospovidone, dibasic calcium phosphate dihydrate, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, red ferric oxide, triacetin and titanium dioxide. <br/> <p class="First">CRESTOR is a trademark of the AstraZeneca group of companies.</p> <br/> Manufactured by: <br/> ScieGen Pharmaceuticals, Inc. <br/> Hauppauge, NY 11788 USA <br/> <br/> For more information, call ScieGen Pharmaceuticals, Inc at 1-855-724-3436. <br/> <br/> Dispense the Patient Information available at: <a href="https://sciegenpharm.com/medicationguide/">https://sciegenpharm.com/medication-guide/</a></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"6%\"/>\n<col align=\"left\" valign=\"top\" width=\"44%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<col align=\"left\" valign=\"top\" width=\"10%\"/>\n<tfoot>\n<tr class=\"First First Last Last\">\n<td align=\"left\" colspan=\"3\">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align=\"right\" colspan=\"1\">Rev:8/2024</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">PATIENT INFORMATION</span>\n<br/> Rosuvastatin Tablets, USP for oral use \n <br/> (roe-SOO-va-STAT-in)\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Read this Patient Information carefully before you start taking rosuvastatin tablets and each time you get a refill. If you have any questions about rosuvastatin tablets, ask your healthcare provider. Only your healthcare provider can determine if rosuvastatin tablets are right for you.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are rosuvastatin tablets?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Rosuvastatin tablets are prescription medicine that contains a cholesterol-lowering medicine called rosuvastatin calcium.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>Rosuvastatin tablets are used:\n \n <ul class=\"Circle\">\n<li>to reduce the risk of major adverse cardiovascular (CV) events, such as death from cardiovascular disease, heart attack, stroke, or the need for procedures to improve blood flow to the heart called arterial revascularization, in adults who do not have known heart disease but do have certain additional risk factors.</li>\n<li>along with diet to:\n \n <ul class=\"Circle\">\n<li>lower the level of low-density lipoprotein (LDL-C) cholesterol or “bad” cholesterol in adults with primary hyperlipidemia.</li>\n<li>slow the buildup of fatty deposits (plaque) in the walls of blood vessels.</li>\n<li>treat adults and children 8 years of age and older with high blood cholesterol due to heterozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).</li>\n</ul>\n</li>\n</ul>\n<ul class=\"Circle\">\n<li>along with other cholesterol lowering treatments or alone if such treatments are unavailable in adults and children 7 years of age and older with homozygous familial hypercholesterolemia (HeFH) (an inherited condition that causes high levels of LDL-C).</li>\n<li>along with diet for the treatment of adults with:\n \n <ul class=\"Circle\">\n<li>primary dysbetalipoproteinemia (an inherited condition that causes high levels of cholesterol and fat).</li>\n<li>hypertriglyceridemia.</li>\n</ul>\n</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">It is not known if rosuvastatin tablets are safe and effective in children younger than 8 years of age with HeFH or children younger than 7 years of age with HoFH or in children with other types of hyperlipidemias (other than HeFH or HoFH).</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Do not take rosuvastatin tablets if you:</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>have liver problems.</li>\n<li>are allergic to rosuvastatin or any of the ingredients in rosuvastatin tablets. See the end of this leaflet for a complete list of ingredients in rosuvastatin tablets. Symptoms of allergic reactions include rash, itching, hives, and swelling.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Before you take rosuvastatin tablets, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have unexplained muscle aches or weakness.</li>\n<li>have or have had kidney problems.</li>\n<li>have or have had liver problems.</li>\n<li>drink more than 2 glasses of alcohol daily.</li>\n<li>have thyroid problems.</li>\n<li>are of Asian descent.</li>\n<li>are pregnant or think you may be pregnant, or are planning to become pregnant. If you become pregnant while taking rosuvastatin tablets, call your healthcare provider right away to discuss your rosuvastatin tablets treatment.</li>\n<li>are breastfeeding. rosuvastatin can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take rosuvastatin tablets. Do not breastfeed while taking rosuvastatin tablets.</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider who prescribes rosuvastatin tablets if another healthcare provider increases the dose of another medicine you are taking.\n \n </p>\n<p>Rosuvastatin tablets may affect the way other medicines work, and other medicines may affect how rosuvastatin tablets works.</p>\n<p>\n<a name=\"Esp\"></a>Especially tell your healthcare provider if you take:</p>\n<ul class=\"Disc\">\n<li>coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)</li>\n<li>antacids (medicines you take for heartburn that contain aluminium and magnesium hydroxide)</li>\n</ul>\n<p>Taking rosuvastatin tablets with certain medicines may increase the risk of muscle problems.</p>\n<p>Especially tell your healthcare provider if you take:</p>\n<ul class=\"Disc\">\n<li>cyclosporine (a medicine for your immune system)</li>\n<li>teriflunomide (a medicine used to treat relapsing remitting multiple sclerosis)</li>\n<li>enasidenib (a medicine used to treat acute myeloid leukemia)</li>\n<li>capmatinib (a medicine for the treatment of non-small cell lung cancer)</li>\n<li>fostamatinib (a medicine used to treat low platelet counts)</li>\n<li>febuxostat (a medicine used to treat and prevent high blood levels of uric acid)</li>\n<li>gemfibrozil (a fibric acid medicine for lowering cholesterol)</li>\n<li>tafamidis (used to treat cardiomyopathy [enlarged and thickened heart muscle])</li>\n<li>anti-viral medicines including certain HIV or hepatitis C virus drugs such as:\n \n <ul class=\"Circle\">\n<li>lopinavir, ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir</li>\n<li>combination of\n \n <ul class=\"Disc\">\n<li>sofosbuvir/velpatasvir/voxilaprevir</li>\n<li>dasabuvir/ombitasvir/paritaprevir/ritonavir</li>\n<li>elbasvir/grazoprevir</li>\n<li>sofosbuvir/velpatasvir</li>\n<li>glecaprevir/pibrentasvir and</li>\n</ul>\n</li>\n<li>all other combinations with ledipasvir including ledipasvir/sofosbuvir</li>\n</ul>\n</li>\n<li>darolutamide (a medicine for the treatment of prostate cancer)</li>\n<li>regorafenib (a medicine used to treat cancer of the colon and rectum)</li>\n<li>fibric acid derivatives (such as fenofibrate)</li>\n<li>ticagrelor (helps reduce the chance of a blood clot formation that can block a blood vessel)</li>\n<li>niacin or nicotinic acid</li>\n<li>colchicine (a medicine used to treat gout)</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get new medicine.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I take rosuvastatin tablets?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>Take rosuvastatin tablets exactly as your healthcare provider tells you to take it.</li>\n<li>Take rosuvastatin tablets, by mouth, 1 time each day. Swallow the tablet whole.</li>\n<li>Rosuvastatin tablets can be taken at any time of day, with or without food.</li>\n<li>\n<span class=\"Bold\">Do not</span>change your dose or stop rosuvastatin tablets without talking to your healthcare provider, even if you are feeling well.\n \n </li>\n<li>Your healthcare provider may do blood tests to check your cholesterol levels before and during your treatment with rosuvastatin tablets. Your healthcare provider may change your dose of rosuvastatin tablets if needed.</li>\n<li>While taking rosuvastatin tablets, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.</li>\n<li>If you take a medicine called an antacid that contains a combination of aluminum and magnesium hydroxide, take rosuvastatin tablets at least 2 hours before you take the antacid.</li>\n<li>If you miss a dose of rosuvastatin tablets, take your next dose at your normal scheduled time.\n \n <span class=\"Bold\">Do not take</span>an extra dose of rosuvastatin tablets.\n \n </li>\n<li>In case of an overdose, get medical help or contact a live Poison Center expert right away at 1-800-222-1222. Advice is also available online at\n \n <a href=\"http://poisonhelp.org\">poisonhelp.org</a>.\n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the possible side effects of rosuvastatin tablets? \n <br/> Rosuvastatin tablets may cause serious side effects, including:\n </span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Muscle pain, tenderness and weakness (myopathy).</span>Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death. Tell your healthcare provider right away if:\n \n <ul class=\"Circle\">\n<li>you have unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel more tired than usual, while you take rosuvastatin tablets.</li>\n<li>you have muscle problems that do not go away even after your healthcare provider has told you to stop taking rosuvastatin tablets. Your healthcare provider may do further tests to diagnose the cause of your muscle problems. \n <br/> Your chances of getting muscle problems are higher if you:\n </li>\n<li>are taking certain other medicines while you take rosuvastatin tablets (see\n \n <a href=\"#Esp\">“Especially tell your healthcare provider if you take”</a>)\n \n </li>\n<li>are 65 years of age or older</li>\n<li>are of Asian descent</li>\n<li>have thyroid problems (hypothyroidism) that are not controlled</li>\n<li>have kidney problems</li>\n<li>are taking higher doses of rosuvastatin tablets</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Liver problems.</span>Your healthcare provider may do blood tests to check your liver before you start taking rosuvastatin tablets and if you have symptoms of liver problems while you take rosuvastatin tablets. Call your healthcare provider right away if you have any of the following symptoms of liver problems:\n \n <ul class=\"Circle\">\n<li>feel unusually tired or weak</li>\n<li>loss of appetite</li>\n<li>upper belly pain</li>\n<li>dark urine</li>\n<li>yellowing of your skin or the whites of your eyes</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Protein and blood in the urine.</span>Rosuvastatin tablets may cause you to have protein and blood in your urine. If you develop protein or blood in your urine, your healthcare provider may decrease your dose of rosuvastatin tablets.\n \n </li>\n<li>\n<span class=\"Bold\">Increase in blood sugar (glucose) levels.</span>Rosuvastatin tablets may cause an increase in your blood sugar levels.\n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">The most common side effects may include headache, nausea, muscle aches and pains, weakness, and constipation.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">For more information, ask your healthcare provider or pharmacist.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I store rosuvastatin tablets?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>Store rosuvastatin tablets at room temperature, between 68°F to 77°F (20°C to 25°C) and in a dry place.</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">Keep rosuvastatin tablets and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">General Information about the safe and effective use of rosuvastatin tablets</span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use rosuvastatin tablets for a condition for which it was not prescribed. Do not give rosuvastatin tablets to other people, even if they have the same medical condition you have. It may harm them. \n <br/> You can ask your pharmacist or healthcare provider for information about rosuvastatin tablets that is written for health professionals.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the Ingredients in Rosuvastatin Tablets, USP?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Active ingredient:</span>rosuvastatin as rosuvastatin calcium, USP (amorphous)\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Inactive ingredients:</span>crospovidone, dibasic calcium phosphate dihydrate, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, red ferric oxide, triacetin and titanium dioxide. \n <br/>\n<p class=\"First\">CRESTOR is a trademark of the AstraZeneca group of companies.</p>\n<br/> Manufactured by: \n <br/> ScieGen Pharmaceuticals, Inc. \n <br/> Hauppauge, NY 11788 USA \n <br/>\n<br/> For more information, call ScieGen Pharmaceuticals, Inc at 1-855-724-3436. \n <br/>\n<br/> Dispense the Patient Information available at:\n \n <a href=\"https://sciegenpharm.com/medicationguide/\">https://sciegenpharm.com/medication-guide/</a></td>\n</tr>\n</tbody>\n</table></div>" }

DRUG: Rosuvastatin

{ "type": "p", "children": [], "text": "DRUG: Rosuvastatin" }

GENERIC: Rosuvastatin

{ "type": "p", "children": [], "text": "GENERIC: Rosuvastatin" }

DOSAGE: TABLET, FILM COATED

{ "type": "p", "children": [], "text": "DOSAGE: TABLET, FILM COATED" }

ADMINSTRATION: ORAL

{ "type": "p", "children": [], "text": "ADMINSTRATION: ORAL" }

NDC: 70518-4296-0

{ "type": "p", "children": [], "text": "NDC: 70518-4296-0" }

NDC: 70518-4296-1

{ "type": "p", "children": [], "text": "NDC: 70518-4296-1" }

NDC: 70518-4296-2

{ "type": "p", "children": [], "text": "NDC: 70518-4296-2" }

NDC: 70518-4296-3

{ "type": "p", "children": [], "text": "NDC: 70518-4296-3" }

COLOR: pink

{ "type": "p", "children": [], "text": "COLOR: pink" }

SHAPE: ROUND

{ "type": "p", "children": [], "text": "SHAPE: ROUND" }

SCORE: No score

{ "type": "p", "children": [], "text": "SCORE: No score" }

SIZE: 8 mm

{ "type": "p", "children": [], "text": "SIZE: 8 mm" }

IMPRINT: SG;118

{ "type": "p", "children": [], "text": "IMPRINT: SG;118" }

PACKAGING: 45 in 1 BOTTLE, PLASTIC

{ "type": "p", "children": [], "text": "PACKAGING: 45 in 1 BOTTLE, PLASTIC" }

PACKAGING: 100 in 1 BOTTLE, PLASTIC

{ "type": "p", "children": [], "text": "PACKAGING: 100 in 1 BOTTLE, PLASTIC" }

PACKAGING: 90 in 1 BOTTLE, PLASTIC

{ "type": "p", "children": [], "text": "PACKAGING: 90 in 1 BOTTLE, PLASTIC" }

PACKAGING: 30 in 1 BLISTER PACK

{ "type": "p", "children": [], "text": "PACKAGING: 30 in 1 BLISTER PACK" }

ACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "ACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "ROSUVASTATIN 20mg in 1" ], "text": "" }

INACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "INACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "CROSPOVIDONE, UNSPECIFIED", "DIBASIC CALCIUM PHOSPHATE DIHYDRATE", "HYPROMELLOSE, UNSPECIFIED", "LACTOSE MONOHYDRATE", "MAGNESIUM STEARATE", "MICROCRYSTALLINE CELLULOSE", "FERRIC OXIDE RED", "TRIACETIN", "TITANIUM DIOXIDE" ], "text": "" }