rosuvstatin

RECENT MAJOR CHANGES Indications and Usage (1) 04/2026 Dosage and Administration, Dosage Modifications Due to Drug Interactions (2.6) 04/2026

1 INDICATIONS AND USAGE Rosuvastatin tablets are 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 at increased risk for CV events. As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C): in adults with hypercholesterolemia. and slow the progression of atherosclerosis in adults. in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). 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: Primary dysbetalipoproteinemia. Hypertriglyceridemia Rosuvastatin tablets are 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 at increased risk for CV events. As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C): reduce LDL-C in adults with primary hypercholesterolemia. 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: Primary dysbetalipoproteinemia. 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 rosuvastatin tablets, 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, 5.1, 8.6) See full prescribing information for rosuvastatin tablets dosage and administration modifications due to drug interactions. (2.6) 2.1 General Dosage and Administration Information Administer rosuvastatin tablets orally as a single dose at any time of day, with or without food. Swallow the tablets whole. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating rosuvastatin tablets, and adjust the dosage if necessary. If a dose is missed, advise patients not take an extra dose. Resume treatment with the next dose. When taking rosuvastatin tablets with an aluminum and magnesium hydroxide combination antacid, administer rosuvastatin tablets at least 2 hours before the antacid [see Drug Interactions (7.2)] . 2.2 Recommended Dosage in Adult Patients The dosage range for rosuvastatin tablets are 5 to 40 mg orally once daily. The recommended dosage of rosuvastatin tablets depends on a patient's indication for usage, LDLC, and individual risk for cardiovascular 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 rosuvastatin tablets at 5 mg orally once daily due to increased rosuvastatin plasma concentrations. Consider the risks and benefits of rosuvastatin tablets when treating Asian patients not adequately controlled at dosages up to 20 mg orally 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 orally once daily and should not exceed 10 mg orally 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 rosuvastatin tablets due to drug interactions [see Warnings and Precautions (5.1) and Drug Interactions (7.1)]. Table 1: Rosuvastatin Tablets Dosage Modifications Due to Drug Interactions Concomitantly Used Drug Rosuvastatin Tablets Dosage Modifications Sofobuvir/velpatasvir/ voxilaprevir or Ledipasvir/sofosbuvir Avoid concomitant use. Gemfibrozil Avoid concomitant use. If use is unavoidable, initiate at 5 mg once daily and do not exceed 10 mg once daily. Tafamidis Avoid concomitant use. If use is unavoidable, initiate at 5 mg once daily and do not exceed 20 mg once daily. Belumosudil Do not exceed 5 mg once daily. Cyclosporine Do not exceed 5 mg once daily. Darolutamide Do not exceed 5 mg once daily. Additional Antiviral Medications o Simeprevir o …

3 DOSAGE FORMS AND STRENGTHS Rosuvastatin tablets, USP: 5 mg of rosuvastatin: yellow colored, round shaped, film-coated biconvex tablets. Debossed with '53' on one side and 'L' on other side. 10 mg of rosuvastatin: pink colored, round shaped, film-coated biconvex tablets. Debossed with '54' on one side and 'L' on other side. 20 mg of rosuvastatin: pink colored, round shaped, film-coated biconvex tablets, debossed with '55' on one side and 'L' on other side. 40 mg of rosuvastatin: pink colored, oval shaped, film-coated biconvex tablets. Debossed with '56' on one side and 'L' on other side. Tablets: 5 mg, 10 mg, 20 mg, and 40 mg of rosuvastatin. (3)

4 CONTRAINDICATIONS Rosuvastatin tablets are contraindicated in patients with: Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3)]. Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin tablets [see Adverse Reactions (6.1)] . Acute liver failure or decompensated cirrhosis. (4) Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. (4)

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 Lifestar Pharma LLC at 1-888-995-4337 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-40 mg N=744 % Headache 5.0 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 4.0 Increased CPK 0.7 2.6 Abdominal pain 1.8 2.4 ALT greater than 3x ULN 2 0.7 2.2 2 Frequency recorded as abnormal laboratory value. 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. Table 4: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in the JUPITER Trial Adverse Reactions Placebo N=8901 % Rosuvastatin 20 mg N=8901 % Myalgia 6.6 7.6 Arthralgia 3.2 3.8 Constipation 3.0 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 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 frequent …

7 DRUG INTERACTIONS See full prescribing information for details regarding concomitant use of rosuvastatin with other drugs that increase the risk of myopathy and rhabdomyolysis. (2.6, 7.1) Aluminum and Magnesium Hydroxide Combination Antacids : Administer rosuvastatin at least 2 hours after the antacid. (2.6, 7.2) Wafarin: Obtain INR prior to starting rosuvastatin. Monitor INR frequently until stable upon initiation, dosage titration or discontinuation. (7.3) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin 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)]. Table 5: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin Sofosbuvir/velpatasvir/voxilaprevir or Ledipasvir/sofosbuvir Prevention or Management: Avoid concomitant use with rosuvastatin. Mechanism and Clinical Effect(s): Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis. Gemfibrozil Prevention or Management: Avoid concomitant use of gemfibrozil with rosuvastatin. If use is unavoidable, initiate rosuvastatin at 5 mg once daily and do not exceed a dosage of rosuvastatin 10 mg once daily. Mechanism and Clinical Effect(s): Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Tafamidis Prevention or Management: Avoid concomitant use of tafamidis with rosuvastatin. If use is unavoidable, initiate rosuvastatin at 5 mg once daily and do not exceed a dosage of rosuvastatin 20 mg once daily. Monitor for signs of myopathy and rhabdomyolysis if used concomitantly with rosuvastatin. Mechanism and Clinical Effect(s): Tafamidis significantly increased rosuvastatin exposure and tafamidis may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Belumosudil Prevention or Management: In patients taking belumosudil, do not exceed a dosage of rosuvastatin 5 mg once daily. Mechanism and Clinical Effect(s): Belumosudil increased rosuvastatin exposure more than 4.6-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Cyclosporine Prevention or Management: In patients taking cyclosporine, do not exceed a dosage of rosuvastatin 5 mg once daily. Mechanism and Clinical Effect(s): Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Darolutamide Prevention or Management: In patients taking darolutamide, do not exceed a dosage of rosuvastatin 5 mg once daily. Mechanism and Clinical Effect(s): Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Additional Anti-Viral Medications Prevention or Management:: Simeprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir Elbasvir/grazoprevir Sofosbuvir/velpatasvir Glecaprevir/pibrentasvir Atazanavir/ritonavir Lopinavir/ritonavir Initiate with rosuvastatin 5 mg once daily, and do not exceed a dosage of rosuvastatin 10 mg once daily. Mechanism and Clinical Effect(s): Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis. Capmatinib Prevention or Management: In patients taking capmatinib, do not exceed a dosage of rosuvastatin 10 mg once daily. Mechanism and Clinical Effect(s): Capm …

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. (8.1) Lactation: Breastfeeding not recommended during treatment with rosuvastatin. (8.2) 8.1 Pregnancy 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 hypercholesterolemia 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 hypercholesterolemia 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 1152 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 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, 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 …

12.1 Mechanism of Action 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.

11 DESCRIPTION Rosuvastatin calcium, USP 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, USP is (C 22 H 27 FN 3 O 6 S) 2 Ca and the molecular weight is 1001.14. Rosuvastatin calcium is a white to off white amorphous powder that is sparingly soluble in methanol, slightly soluble in water and practically insoluble in ethanol. Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 0.13 at pH of 7.0. Rosuvastatin tablets, USP for oral use contain 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) and the following inactive ingredients: dibasic calcium phosphate anhydrous, crospovidone, ferric oxide red (for 10 mg, 20 mg and 40 mg tablets), ferric oxide yellow (for 5 mg tablets), hypromellose 2910 (15 mpa.s), lactose anhydrous, lactose monohydrate, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin. strucural formula

10 OVERDOSAGE No specific antidotes for rosuvastatin tablets 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.

16 HOW SUPPLIED/STORAGE AND HANDLING Rosuvastatin tablets, USP are supplied as: 5 mg: Yellow colored, round shaped, film-coated biconvex tablets, debossed with '53' on one side and 'L' on other side. NDC 70756-053-90 bottles of 90 with child-resistant closure NDC 70756-053-12 bottles of 1000 10 mg: Pink colored, round shaped, film-coated biconvex tablets, debossed with '54' on one side and 'L' on other side. NDC 70756-054-90 bottles of 90 with child-resistant closure NDC 70756-054-12 bottles of 1000 20 mg: Pink colored, round shaped, film-coated biconvex tablets, debossed with '55' on one side and 'L' on other side. NDC 70756-055-90 bottles of 90 with child-resistant closure NDC 70756-055-12 bottles of 1000 40 mg: Pink colored, oval shaped, film-coated biconvex tablets, debossed with '56' on one side and 'L' on other side. NDC 70756-056-30 bottles of 30 with child-resistant closure NDC 70756-056-90 bottles of 90 with child-resistant closure NDC 70756-056-12 bottles of 1000 Storage Store at 20oC to 25oC (68oF to 77oF); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from moisture.