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) ≥2 mg/L, and at least one additional CV risk factor.
As an adjunct to diet to: o reduce 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. 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) ≥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.
Contraindications
Acute liver failure or decompensated cirrhosis. ( 4 ) Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. ( 4 ) Rosuvastatin tablets are contraindicated in the following conditions:
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 ) ] .
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 )
5.1Myopathy and Rhabdomyolysis
Rosuvastatin tablets 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 tablets. 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 tablets dosage.
Asian patients on rosuvastatin tablets 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 tablets 40 mg daily compared with lower rosuvastatin tablets dosages. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis The concomitant use of rosuvastatin tablets with cyclosporine or gemfibrozil is not recommended. rosuvastatin tablets 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 tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin tablets are discontinued. Temporarily discontinue rosuvastatin tablets 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 tablets dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
5.2Immune-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 tablets if IMNM is suspected.
5.3Hepatic Dysfunction Increases
in serum transaminases have been reported with use of rosuvastatin tablets [ 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 tablets versus 0.5% of patients treated with placebo.
Marked persistent increases of hepatic transaminases have also occurred with rosuvastatin tablets. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin tablets. 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 tablets initiation and when clinically indicated thereafter. Rosuvastatin tablets are 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 tablets.
5.4 Proteinuria and Hematuria In the rosuvastatin tablets clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among rosuvastatin tablets treated patients. These findings were more frequent in patients taking rosuvastatin tablets 40 mg, when compared to lower doses of rosuvastatin tablets 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 tablets therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.
5.5Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c
and fasting serum glucose levels have been reported with statins, including rosuvastatin tablets. Based on clinical trial data with rosuvastatin tablets, 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.
Interactions
See full prescribing information for details regarding concomitant use of rosuvastatin tablets with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 7.1 ) Aluminum and Magnesium Hydroxide Combination Antacids : Administer rosuvastatin tablets at least 2 hours before the antacid. ( 7.2 ) Warfarin : Obtain INR prior to starting rosuvastatin tablets. Monitor INR frequently until stable upon initiation, dose titration or discontinuation.( 7.3 )
7.1Drug
Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin Tablets 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 tablets 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 Tablets Cyclosporine Clinical Impact: Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with rosuvastatin tablets. Intervention: If used concomitantly, do not exceed a dose of rosuvastatin tablets 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. Intervention: In patients taking teriflunomide, do not exceed a dose of rosuvastatin tablets 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.
Intervention: In patients taking enasidenib, do not exceed a dose of rosuvastatin tablets 10 mg once daily. Capmatinib Clinical Impact: Capmatinib increased rosuvastatin exposure more than 2.1-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking capmatinib, do not exceed a dose of rosuvastatin tablets 10 mg once daily . Fostamatinib Clinical Impact: Fostamatinib increased rosuvastatin exposure more than 2.0-fold.
The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking fostamatinib, do not exceed a dose of rosuvastatin tablets 20 mg once daily . Febuxostat Clinical Impact: Febuxostat increased rosuvastatin exposure more than 1.9-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking febuxostat, do not exceed a dose of rosuvastatin tablets 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 rosuvastatin tablets. Intervention: Avoid concomitant use of gemfibrozil with rosuvastatin tablets. If used concomitantly, initiate rosuvastatin tablets at 5 mg once daily and do not exceed a dose of rosuvastatin tablets 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 rosuvastatin tablets. Intervention: Avoid concomitant use of tafamidis with rosuvastatin tablets. If used concomitantly, initiate rosuvastatin tablets at 5 mg once daily and do not exceed a dose of rosuvastatin tablets 20 mg once daily.
Monitor for signs of myopathy and rhabdomyolysis if used concomitantly with rosuvastatin tablets . Anti-Viral 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. Intervention: Sofosbuvir/velpatasvir/voxilaprevir Ledipasvir/sofosbuvir Avoid concomitant use with rosuvastatin tablets.
Simeprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir Elbasvir/grazoprevir Sofosbuvir/velpatasvir Glecaprevir/pibrentasvir Atazanavir/ritonavir Lopinavir/ritonavir Initiate with rosuvastatin tablets 5 mg once daily, and do not exceed a dose of rosuvastatin tablets 10 mg once daily. Darolutamide Clinical Impact: Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use .
Intervention: In patients taking darolutamide, do not exceed a dose of rosuvastatin tablets 5 mg once daily . Regorafenib Clinical Impact: Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy. Intervention: In patients taking regorafenib, do not exceed a dose of rosuvastatin tablets 10 mg once daily . Fenofibrates (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 rosuvastatin tablets. Intervention: Consider if the benefit of using fibrates concomitantly with rosuvastatin tablets 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.
Niacin Clinical Impact: Cases of myopathy and rhabdomyolysis have occurred with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with rosuvastatin tablets. Intervention: Consider if the benefit of using lipid-modifying doses (≥1 g/day) of niacin concomitantly with rosuvastatin tablets 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.
Colchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with rosuvastatin tablets. Intervention: Consider if the benefit of using colchicine concomitantly with rosuvastatin tablets 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 rosuvastatin tablets 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. Intervention: 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 rosuvastatin tablets.
7.2Drug
Interactions that Decrease the Efficacy of Rosuvastatin Tablets Table 6 presents drug interactions that may decrease the efficacy of rosuvastatin tablets and instructions for preventing or managing them. Table 6: Drug Interactions that Decrease the Efficacy of Rosuvastatin Tablets Antacids Clinical Impact: Concomitant aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% [see Clinical Pharmacology (12.3) ].
Intervention: In patients taking antacid, administer rosuvastatin tablets at least 2 hours before the antacid .
7.3Rosuvastatin Tablets Effects on Other Drugs Table
7 presents rosuvastatin tablet's effect on other drugs and instructions for preventing or mana
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Adverse reactions
Most frequent adverse reactions (rate ≥2%) are headache, nausea, myalgia, asthenia, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 ) ]
6.1Clinical 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 Tablets and > Placebo in Placebo-Controlled Trials Adverse Reactions Placebo N=382% 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% 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 tablets 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 Tablets and > Placebo in the METEOR Trial 1 Frequency recorded as abnormal laboratory value.
2.2 In the JUPITER study, patients were treated with rosuvastatin tablets 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 tablets (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin tablets-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 tablets-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 Tablets and > Placebo in the JUPITER Trial Adverse Reactions Placebo N=8,901% Rosuvastatin tablets 20 mg N=8,901% 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 tablets 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 tablets-treated patients compared with patients receiving placebo. Four of 130 (3%) patients treated with rosuvastatin tablets (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.
6.2Postmarketing Experience
The following adverse reactions have been identified during postapproval use of rosuvastatin tablets. 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
Composition
Active ingredients
ROSUVASTATIN CALCIUM EQ 5MG BASE
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
