Rosuvastatin Calcium
Generic: ROSUVASTATIN CALCIUM
Basic Information
Manufacturer
Proficient Rx LP
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
3066f572-e3db-4bf8-b9ee-bd32d9ed8c13
Indications & Usage
1 INDICATIONS AND USAGE Pediatric use information for patients 7 to 17 years of age is approved for AstraZeneca’s CRESTOR (rosuvastatin calcium) tablets.
However, due to AstraZeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Rosuvastatin calcium tablets are 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 calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias.
1.3 Hypertriglyceridemia Rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.
1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) Rosuvastatin calcium 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 calcium 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 calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias.
However, due to AstraZeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Rosuvastatin calcium tablets are 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 calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias.
1.3 Hypertriglyceridemia Rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.
1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) Rosuvastatin calcium 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 calcium 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 calcium tablets have not been studied in Fredrickson Type I and V dyslipidemias.
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: • Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see Warnings and Precautions (5.1) ] • Liver enzyme abnormalities [see Warnings and Precautions (5.2) ] Most frequent adverse reactions (rate ≥2%) are headache, myalgia, abdominal pain, asthenia, and nausea.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Citron Pharma LLC.
at 1-855-5-CITRON (1-855-524-8766) 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 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 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 Reactions 1 Reported in ≥ 2% of Patients Treated with Rosuvastatin and > Placebo in Placebo-Controlled Trials (% of Patients) 1 Adverse reactions by COSTART preferred term.
Adverse Reactions 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 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 Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema) and pancreatitis.
The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [see Warnings and Precautions (5.4)] ; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.
In a clinical trial, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years, 5.6% of subjects treated with rosuvastatin versus 2.8% of placebo-treated subjects discontinued due to adverse reactions.
The most common adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased, headache, and nausea.
Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 2.
Table 2.
Adverse Reactions 1 Reported in ≥ 2% of Patients Treated with Rosuvastatin and > Placebo in a Trial (% of Patients) 1 Adverse reactions by MedDRA preferred term.
2 Frequency recorded as abnormal laboratory value.
Adverse Reactions Rosuvastatin 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 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 (5.5)] .
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 and > Placebo in a Trial (% of Patients) 1 Treatment-emergent adverse reactions by MedDRA preferred term.
Adverse Reactions Rosuvastatin 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 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of rosuvastatin: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares), peripheral neuropathy and gynecomastia.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1) ] .
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, 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).
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Citron Pharma LLC.
at 1-855-5-CITRON (1-855-524-8766) 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 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 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 Reactions 1 Reported in ≥ 2% of Patients Treated with Rosuvastatin and > Placebo in Placebo-Controlled Trials (% of Patients) 1 Adverse reactions by COSTART preferred term.
Adverse Reactions 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 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 Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema) and pancreatitis.
The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [see Warnings and Precautions (5.4)] ; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.
In a clinical trial, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years, 5.6% of subjects treated with rosuvastatin versus 2.8% of placebo-treated subjects discontinued due to adverse reactions.
The most common adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased, headache, and nausea.
Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 2.
Table 2.
Adverse Reactions 1 Reported in ≥ 2% of Patients Treated with Rosuvastatin and > Placebo in a Trial (% of Patients) 1 Adverse reactions by MedDRA preferred term.
2 Frequency recorded as abnormal laboratory value.
Adverse Reactions Rosuvastatin 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 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 (5.5)] .
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 and > Placebo in a Trial (% of Patients) 1 Treatment-emergent adverse reactions by MedDRA preferred term.
Adverse Reactions Rosuvastatin 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 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of rosuvastatin: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares), peripheral neuropathy and gynecomastia.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1) ] .
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, 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).