Generic: ROSUVASTATIN
HMG-CoA Reductase Inhibitor [EPC]
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 without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) โฅ2 mg/L, and at least one additional CV risk factor. As an adjunct to diet to: Reduce low-density lipoprotein cholesterol ...
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 without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) โฅ2 mg/L, and at least one additional CV risk factor. As an adjunct to diet to: Reduce low-density lipoprotein cholesterol (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: Primary dysbetalipoproteinemia. Hypertriglyceridemia. Rosuvastatin tablets are 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) โฅ2 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: Primary dysbetalipoproteinemia. Hypertriglyceridemia.
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 rosuvastatin tablets dosage. Asian patients may be at higher risk for myopathy. Discontinue rosuvastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue rosuvastatin tablets in patients experiencing an acute or serious condition at high r...
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 rosuvastatin tablets dosage. Asian patients may be at higher risk for myopathy. Discontinue rosuvastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue rosuvastatin tablets 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 rosuvastatin tablets 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 rosuvastatin tablets 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 rosuvastatin tablets. ( 5.3 ) 5.1 Myopathy and Rhabdomyolysis 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. 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 rosuvastatin if IMNM is suspected. 5.3 Hepatic Dysfunction 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. 5.4 Proteinuria and Hematuria 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. 5.5 Increases in HbA1c and Fasting Serum Glucose Levels 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.
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 (r...
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 โฅ 2%) are headache, nausea, myalgia, asthenia, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ScieGen Pharmaceuticals, Inc., at 1-855-724-3436 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 โฅ2% 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 โฅ2% 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 5.0 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 โฅ2% of patients and at a rate greater than placebo are shown in Table 3. Table 3: Adverse Reactions Reported in โฅ 2% of Patients Treated with Rosuvastatin and > Placebo in the METEOR Trial Adverse Reactions Placebo N=281% Rosuvastatin 40 mg N=700% 1 Frequency recorded as abnormal laboratory value. 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 1 0.7 2.2 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 โฅ 2% of patients and at a rate greater than placebo are shown in Table 4. Table 4: Adverse Reactions Reported in โฅ 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 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
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.