1 INDICATIONS & USAGE Pediatric use information for patients 7 to 17 years of age is approved for AstraZeneca’s CRESTOR (rosuvastatin calcium) tablets.

However, due to AstraZeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Rosuvastatin tablets is an HMG Co-A reductase inhibitor indicated for: adult patients with hypertriglyceridemia as an adjunct to diet ( 1.

3) adult patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet ( 1.

4) adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB ( 1.

5)Limitations of use ( 1.

8): Rosuvastatin tablets has not been studied in Fredrickson Type I and V dyslipidemias.

1.3 Hypertriglyceridemia Rosuvastatin tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.

1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) Rosuvastatin tablets are indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).

1.5 Adult Patients with Homozygous Familial Hypercholesterolemia Rosuvastatin tablets are indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL–C, Total–C, and ApoB in adult patients with homozygous familial hypercholesterolemia.

1.8 Limitations of Use Rosuvastatin tablets has not been studied in Fredrickson Type I and V dyslipidemias.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: • Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [ see Warnings and Precautions ( 5.1 )] • Liver enzyme abnormalities [ see Warnings and Precautions ( 5.3 )] Most frequent adverse reactions (rate ≥2%) are headache, myalgia, abdominal pain, asthenia, and nausea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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

In the rosuvastatin tablets controlled clinical trials database (placebo or active-controlled) of 5394 patients with a mean treatment duration of 15 weeks, 1.4% of patients discontinued due to adverse reactions.

The most common adverse reactions that led to treatment discontinuation were: • myalgia • abdominal pain • nausea The most commonly reported adverse reactions (incidence ≥ 2%) in the rosuvastatin tablets controlled clinical trial database of 5394 patients were: • headache • myalgia • abdominal pain • asthenia • nausea Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 1.

These studies had a treatment duration of up to 12 weeks.

Table 1.

Adverse Reactions1 Reported in ≥ 2% of Patients Treated with rosuvastatin tablets and > Placebo in Placebo–Controlled Trials (% of Patients) Adverse Reactions Rosuvastatin tablets 5 mg N=291 Rosuvastatin tablets 10 mg N=283 Rosuvastatin tablets 20 mg N=64 Rosuvastatin tablets 40 mg N=106 Total rosuvastatin tablets 5 mg to 40 mg N=744 Placebo N=382 Headache 5.5 4.9 3.1 8.5 5.5 5.0 Nausea 3.8 3.5 6.3 0 3.4 3.1 Myalgia 3.1 2.1 6.3 1.9 2.8 1.3 Asthenia 2.4 3.2 4.7 0.9 2.7 2.6 Constipation 2.1 2.1 4.7 2.8 2.4 2.4 1 Adverse reactions by COSTART preferred term.

Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria,and angioedema) and pancreatitis.

The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [ see Warnings and Precautions ( 5.5 ) ]; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.

In a clinical trial, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years, 5.6% of subjects treated with rosuvastatin tablets versus 2.8% of placebo-treated subjects discontinued due to adverse reactions.

The most common adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased,headache, and nausea.

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

Table 2.

Adverse Reactions 1 Reported in ≥ 2% of Patients Treated with rosuvastatin tablets and > Placebo in a Trial (% of Patients) Adverse Reactions Rosuvastatin tablets 40 mg N=700 Placebo N=281 Myalgia 12.7 12.1 Arthralgia 10.1 7.1 Headache 6.4 5.3 Dizziness 4.0 2.8 Increased CPK 2.6 0.7 Abdominal pain 2.4 1.8 ALT >3x ULN 2 2.2 0.7 1 Adverse reactions by MedDRA preferred term.

2 Frequency recorded as abnormal laboratory value.

In a clinical trial, 17,802 participants were treated with rosuvastatin 20 mg (n=8901) or placebo (n=8901) for a mean duration of 2 years.

A higher percentage of rosuvastatin-treated patients versus placebo-treated patients, 6.6% and 6.2%, respectively,discontinued study medication due to an adverse event, irrespective of treatment causality.

Myalgia was the most common adverse reaction that led to treatment discontinuation.

There was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%).

Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients.

The number of patients with a HbA1c > 6.5% at the end of the trial was significantly higher in rosuvastatin treated versus placebo-treated patients [ see Warnings and Precautions ( 5.6 ) ].

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

Table 3.

Adverse Reactions 1 Reported in ≥ 2% of Patients Treated with rosuvastatin tablets and > Placebo in a Trial (% of Patients) Adverse Reactions Rosuvastatin tablets 20 mg N=8901 Placebo N=8901 Myalgia 7.6 6.6 Arthralgia 3.8 3.2 Constipation 3.3 3.0 Diabetes mellitus 2.8 2.3 Nausea 2.4 2.3 1 Treatment-emergent adverse reactions by MedDRA preferred term.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of rosuvastatin tablets: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares),peripheral neuropathy,interstitial lung disease and gynecomastia.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [ see Warnings and Precautions ( 5.2 ) ].

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment and confusion) associated with statin use.

These cognitive issues have been reported for all statins.

The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).