EZALLOR SPRINKLE

1 INDICATIONS AND USAGE 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). • 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. EZALLOR SPRINKLE is an HMG Co-A reductase inhibitor (statin) indicated: (1) 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: reduce LDL-C in adults with primary hyperlipidemia. reduce LDL-C and slow the progression of atherosclerosis in adults. 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). As an adjunct to diet for the treatment of adults with: o Primary dysbetalipoproteinemia. o Hypertriglyceridemia.

2 DOSAGE AND ADMINISTRATION Take orally with or without food, at any time of day. (2.1) Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating EZALLOR SPRINKLE, and adjust dosage if necessary. (2.1) Adults: Recommended dosage range is 5 to 40 mg once daily. (2.1) Pediatric Patients with HeFH: Recommended dosage range is 5 to 10 mg once daily for patients aged 8 to less than 10 years of age, and 5 to 20 mg once daily for patients aged 10 years and older. (2.2) Pediatric Patients with HoFH: Recommended dosage is 20 mg once daily for patients aged 7 years and older. (2.2) Asian Patients: Initiate at 5 mg once daily. Consider risks and benefits of treatment if not adequately controlled at doses up to 20 mg once daily. (2.4) Patients with Severe Renal Impairment (not on hemodialysis): Initiate at 5 mg once daily; do not exceed 10 mg once daily. (2.5) See full prescribing information for EZALLOR SPRINKLE dosage and administration modifications due to drug interactions. (2.6) 2.1 General Dosage and Administration Information Administer EZALLOR SPRINKLE orally as a single dose at any time of day, with or without food. Swallow the capsules whole. Do not crush or chew. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating EZALLOR SPRINKLE, and adjust the dosage if necessary. If a dose is missed, advise patients not to take an extra dose. Resume treatment with the next dose. 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)]. 2.2 Recommended Dosage in Adult Patients The dosage range for EZALLOR SPRINKLE is 5 mg to 40 mg orally once daily. The recommended dose of EZALLOR SPRINKLE depends on a patient’s indication for usage, LDL-C, and individual risk for CV events. 2.3 Recommended Dosage in Pediatric Patients 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. 2.4 Recommended Dosage in Asian Patients 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)]. 2.5 Recommended Dosage in Patients with Renal Impairment In patients with severe renal impairment (CLcr less 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. 2.6 Dosage Modifications Due to Drug Interactions 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 Concomitantly Used Drug EZALLOR SPRINKLE Dosage Modifications Cyclosporine Do not exceed 5 mg once daily. Teriflunomide Do not exceed 10 mg once daily. Enasidenib Do not exceed 10 mg once daily. Capmatinib Do not exceed 10 mg once daily. Fostamatinib Do not exceed 20 mg once daily. Febuxostat Do not exceed 20 mg once daily. Gemfibrozil Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily. Tafamidis Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 20 mg once daily. Antiviral Medications Sofosbuvir/velpatasvir/voxilaprevir Ledipasvir/sofosbuvir Concomitant use not recommended. Simeprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir Elbasvir/Grazoprevir Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Atazanavir/Ritonavir Lopinavir/Ritonavir Initiate at 5 mg once daily. Do not exceed 10 mg once daily. Darolutamide Do not exceed 5 mg once daily. Regorafenib Do not exceed 10 mg once daily. 2.7 Preparation and Administration Instructions 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 Carefully open the capsule and sprinkle the entire contents of the capsule onto at least one teaspoonful (5 mL) of room temperature applesauce or chocolate/vanilla flavored pudding. Stir the mixture for 10 to 15 seconds. Swallow the entire mixture within 60 minutes of mixing. Do not chew the mixture. Do not save the mixture for later use. Discard the unused portion immediately. Nasogastric Tube (≥16 French) Administration Carefully open the capsule and empty the intact granules emptied into a 60 mL catheter tipped syringe barrel and add 40 mL of water. Do not use with liquids other than water. Replace the plunger and shake the syringe vigorously for 15 seconds. The granules in EZALLOR SPRINKLE capsule may start dissolving which is acceptable. Attach the syringe to a nasogastric tube (≥16-French) and deliver the contents of the syringe through the nasogastric tube into the stomach. Flush the nasogastric tube should with 20 mL of additional water after administering the mixture. Do not save the mixture for later use. Discard the unused portion immediately.

4 CONTRAINDICATIONS EZALLOR SPRINKLE is contraindicated in patients with: Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3)]. 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)] . Acute liver failure or decompensated cirrhosis. (4) Hypersensitivity to rosuvastatin or any excipients in EZALLOR SPRINKLE. (4)

5 WARNINGS AND PRECAUTIONS Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher EZALLOR SPRINKLE dosage. Asian patients may be at higher risk for myopathy. Discontinue EZALLOR SPRINKLE if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue EZALLOR SPRINKLE in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing EZALLOR SPRINKLE dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. (5.1) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported with statin use. Discontinue EZALLOR SPRINKLE if IMNM is suspected. (5.2) Hepatic Dysfunction : Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue EZALLOR SPRINKLE. (5.3) 5.1 Myopathy and Rhabdomyolysis 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. 5.2 Immune-Mediated Necrotizing Myopathy 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. 5.3 Hepatic Dysfunction 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. 5.4 Proteinuria and Hematuria In the rosuvastatin clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among rosuvastatin treated patients. These findings were more frequent in patients taking rosuvastatin 40 mg, when compared to lower doses of rosuvastatin or comparator 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. 5.5 Increases in HbA1c and Fasting Serum Glucose Levels 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.

7 DRUG INTERACTIONS See full prescribing information for details regarding concomitant use of EZALLOR SPRINKLE with other drugs that increase the risk of myopathy and rhabdomyolysis. (7.1) Aluminum and Magnesium Hydroxide Combination Antacids: Administer EZALLOR SPRINKLE at least 2 hours before the antacid. (7.2) Warfarin: Obtain INR prior to starting EZALLOR SPRINKLE. Monitor INR frequently until stable upon initiation, dose titration or discontinuation. (7.3) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with EZALLOR SPRINKLE 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 C yclosporine Clinical Impact: Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with EZALLOR SPRINKLE. I ntervention: If used concomitantly, do not exceed a dose of EZALLOR SPRINKLE 5 mg once daily . Teriflunomide Clinical Impact: Teriflunomide increased rosuvastatin exposure more than 2.5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. I ntervention: In patients taking teriflunomide, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily . Enasidenib Clinical Impact: Enasidenib increased rosuvastatin exposure more than 2.4-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. I ntervention: In patients taking enasidenib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily . C apmatinib Clinical Impact: Capmatinib increased rosuvastatin exposure more than 2.1-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. I ntervention: In patients taking capmatinib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily . F ostamatinib Clinical Impact: Fostamatinib increased rosuvastatin exposure more than 2-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. I ntervention: In patients taking fostamatinib, do not exceed a dose of EZALLOR SPRINKLE 20 mg once daily . Fe buxostat Clinical Impact: Febuxostat increased rosuvastatin exposure more than 1.9-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. I ntervention: In patients taking febuxostat, do not exceed a dose of EZALLOR SPRINKLE 20 mg once daily . Gemfibrozil Clinical Impact: 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. I ntervention: 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 . Tafamidis Clinical Impact: 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. I ntervention: 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 . A n t i-Vi r a l Medications Clinical Impact: Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis. I ntervention: Sofosbuvir/velpatasvir/voxilaprevir Ledipasvir/sofosbuvir Avoid concomitant use with EZALLOR SPRINKLE. Simeprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir Elbasvir/grazoprevir Sofosbuvir/velpatasvir Glecaprevir/pibrentasvir Atazanavir/ritonavir Lopinavir/ritonavir Initiate with EZALLOR SPRINKLE 5 mg once daily, and do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily. D arolutamide Clinical Impact: Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use . I ntervention: In patients taking darolutamide, do not exceed a dose of EZALLOR SPRINKLE 5 mg once daily . Re gorafenib Clinical Impact: Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy. I ntervention: In patients taking regorafenib, do not exceed a dose of EZALLOR SPRINKLE 10 mg once daily . Fe nofibrates (e.g., fenofibrate and fenofibric acid) Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with EZALLOR SPRINKLE I ntervention: 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. N iacin Clinical Impact: Cases of myopathy and rhabdomyolysis have occurred with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with EZALLOR SPRINKLE. I ntervention: 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. C olchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with EZALLOR SPRINKLE. I ntervention: 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. Ticagrelor Clinical Impact: 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. I ntervention: 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. 7.2 Drug Interactions that Decrease the Efficacy of EZALLOR SPRINKLE 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 A ntacids Clinical Impact: Concomitant aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% [see Clinical Pharmacology (12.3)] . I ntervention: In patients taking antacid, administer EZALLOR SPRINKLE at least 2 hours before the antacid. 7.3 EZALLOR SPRINKLE Effects on Other Drugs Table 7 presents EZALLOR SPRINKLE effect on other drugs and instructions for preventing or managing them. Table 7: Rosuvastatin Effects on Other Drugs Warfarin Clinical Impact: Rosuvastatin significantly increased the INR in patients receiving warfarin [see Clinical Pharmacology (12.3)] . I ntervention: 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.

6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.1)] Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions (5.2)] Hepatic Dysfunction [see Warnings and Precautions (5.3)] Proteinuria and Hematuria [see Warnings and Precautions (5.4)] Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions (5.5)] Most frequent adverse reactions (rate ≥ 2%) are headache, nausea, myalgia, asthenia, and constipation. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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 Adverse Reactions Placebo N=382 % Rosuvastatin 5 mg N=291 % Rosuvastatin 10 mg N=283 % Rosuvastatin 20 mg N=64 % Rosuvastatin 40 mg N=106 % Total Rosuvastatin 5 mg to 40 mg N=744 % Headache 5 5.5 4.9 3.1 8.5 5.5 Nausea 3.1 3.8 3.5 6.3 0 3.4 Myalgia 1.3 3.1 2.1 6.3 1.9 2.8 Asthenia 2.6 2.4 3.2 4.7 0.9 2.7 Constipation 2.4 2.1 2.1 4.7 2.8 2.4 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 Adverse Reactions Placebo N=281 % Rosuvastatin 40 mg N=700 % Myalgia 12.1 12.7 Arthralgia 7.1 10.1 Headache 5.3 6.4 Dizziness 2.8 4 Increased CPK 0.7 2.6 Abdominal pain 1.8 2.4 ALT greater than 3x ULN 1 0.7 2.2 1 Frequency 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 Adverse Reactions Placebo N=8,901 % Rosuvastatin 20 mg N=8,901 % Myalgia 6.6 7.6 Arthralgia 3.2 3.8 Constipation 3 3.3 Diabetes mellitus 2.3 2.8 Nausea 2.3 2.4 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. 6.2 Postmarketing Experience 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

8.1 Pregnancy 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/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 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.