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Indications/Uses
5 mg: Hyperlipidemia and Mixed Dyslipidemia: Used to reduced LDL cholesterol, apolipoprotein B, and triglycerides, and to increase HDLcholesterol in the management of hyperlipidemias, including primary hypercholesterolaemia (type lla), mixed dyslipidaemia (type llb), and Hypertriglyceridemia (type IV), as well as in patients with homozygous familial hypercholesterolaemia.
It is also used to reduce the progression of atherosclerosis.
Homozygous Familial Antihyperlipidemic: Rosuvastatin is indicated as adjunctive therapy to the 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 hyperlipidemia.
Slowing of the progression of the atherosclerosis: Rosuvastatin is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients is a part of a treatment strategy to lower Total-C and V dyslipidemias.
Limitations of use: The effect of Rosuvastatin on cardiovascular morbidity and mortality has not been determined.
Rosuvastatin has not been studied in Fredrickson Type I, III, and V dyslipidemias.
10 mg & 20 mg: Patients suffering from primary hypercholesterolemia (type IIa indicating homozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) or in patients suffering from homozygous familial hypercholesterolemia as an adjunct to diet when response to diet and other non-pharmacological treatments (eg, exercise, weight reduction) is inadequate.
40 mg: Hyperlipidemia and Mixed Dyslipidemia: Rosuvastatin is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate.
Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH): Adjunct to diet to reduce Total-C, LDL-C, and ApoB levels in adolescent boys and girls, who are at least one year postmenarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C> 190 mg/dl or >160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors.
Hypertriglyceridemia: Rosuvastatin is indicated as an adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.
Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia): Rosuvastatin is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).
Homozygous Familia Hypercholesterolemia: Rosuvastatin is 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.
Slowing of the Progression of Atherosclerosis: Rosuvastatin is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels.
Primary Prevention of Cardiovascular Disease: In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age>50 years old in men and > 60 years old in women, hsCRP > 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, Rosuvastatin is indicated to: reduce the risk of stroke, reduce the risk of myocardial infarction, reduce the risk of arterial revascularization procedures.
Limitations of Use: Rosuvastatin has not been studied in Fredrickson Type I and V dyslipidemias.
It is also used to reduce the progression of atherosclerosis.
Homozygous Familial Antihyperlipidemic: Rosuvastatin is indicated as adjunctive therapy to the 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 hyperlipidemia.
Slowing of the progression of the atherosclerosis: Rosuvastatin is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients is a part of a treatment strategy to lower Total-C and V dyslipidemias.
Limitations of use: The effect of Rosuvastatin on cardiovascular morbidity and mortality has not been determined.
Rosuvastatin has not been studied in Fredrickson Type I, III, and V dyslipidemias.
10 mg & 20 mg: Patients suffering from primary hypercholesterolemia (type IIa indicating homozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) or in patients suffering from homozygous familial hypercholesterolemia as an adjunct to diet when response to diet and other non-pharmacological treatments (eg, exercise, weight reduction) is inadequate.
40 mg: Hyperlipidemia and Mixed Dyslipidemia: Rosuvastatin is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate.
Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH): Adjunct to diet to reduce Total-C, LDL-C, and ApoB levels in adolescent boys and girls, who are at least one year postmenarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C> 190 mg/dl or >160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors.
Hypertriglyceridemia: Rosuvastatin is indicated as an adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.
Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia): Rosuvastatin is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).
Homozygous Familia Hypercholesterolemia: Rosuvastatin is 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.
Slowing of the Progression of Atherosclerosis: Rosuvastatin is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels.
Primary Prevention of Cardiovascular Disease: In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age>50 years old in men and > 60 years old in women, hsCRP > 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, Rosuvastatin is indicated to: reduce the risk of stroke, reduce the risk of myocardial infarction, reduce the risk of arterial revascularization procedures.
Limitations of Use: Rosuvastatin has not been studied in Fredrickson Type I and V dyslipidemias.
Dosage/Direction for Use
5 mg: The usual initial dose of Rosuvastatin is 5 mg or 10 mg once daily, depending on plasma-cholesterol concentrations, cardiovascular risk factors for adverse effects. The maintenance dose ranges from 5 mg to 40 mg once daily although the 40 mg dose is reserved for patients with high cardiovascular risk who do not achieved their target cholesterol concentration at lower doses and who do not have risk factors for adverse effects. Specific dosage recommendations vary; for dosage in renal impairment.
10 mg & 20 mg: The patient should be placed on a standard cholesterol-lowering diet before receiving rosuvastatin and should continue on this diet during treatment with Zyrova. Rosuvastatin may be given as a single dose at any time of the day, with or without food. The dose of rosuvastatin should be individualized according to the goal of therapy and patient response.
Usual Recommended Dose: Starting Dosage: 10 mg once daily.
Initiation of therapy with 5 mg once daily may be considered for patients requiring less aggressive LDL-C reductions or who have predisposing factors for myopathy.
Marked Hypercholesterolemia (LDL-C >190 mg/dL) and Aggressive Targets: Starting Dose: 20 mg. The 40-mg dose should be reserved for those patients who have not achieved goal LDL-C at 20 mg. After initiation and/or upon titration of rosuvastatin, lipid levels should be analyzed within 2-4 weeks and dosage adjusted accordingly.
Renal Impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment. For patients with severe renal impairment (CrCl <30 mL/min/m2) not on hemodialysis, dosing of rosuvastatin should be started at 5 mg once daily and not to exceed 10 mg once daily.
In patients taking cyclosporine therapy, therapy should be limited to 5 mg once daily. If rosuvastatin is used in combination with gemfibrozil, the dose should be limited to 10 mg once daily.
40 mg: General Dosing Information: The dose range for Rosuvastatin is 5 to 40 mg orally once daily. The usual starting dose is 10 - 20 mg. Rosuvastatin can be administered as a single dose at any time time of day, with or without food. When initiating Rosuvastatin therapy or switching from another HMG-CoA reductase inhibitor therapy, the appropriate Rosuvastain starting dose should first be utilized, and only then titrated according to the patient's response and individualized goal of therapy.
After initiation or upon titration of Rosuvastatin, lipid levels should be analyzed within 2 to 4 weeks and the dosage adjusted accordingly.
The 40 mg dose of Rosuvastatin should be used only for those patients who have not achieved their LDL-C goal utilizing the 20 mg dose.
Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age): The usual dose range of Rosuvastatin is 5-20 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
Homozygous Familial Hypercholesterolemia: The recommended starting dose of Rosuvastatin is 20 mg once daily. Response to therapy should be estimated from preapheresis LDL-C levels.
Dosing in Asian Patients: In Asian patients, consider initiation of Rosuvastatin therapy with 5 mg once daily due to increased rosuvastatin plasma concentrations. The increased systemic exposure should be taken into consideration when treating Asian patients not adequately controlled at doses up to 20 mg/day.
Use with Concomitant Therapy: Patients taking cyclosporine: The dose of Rosuvastatin should not exceed 5 mg once daily.
Patients taking gemfibrozil: Initiate Rosuvastatin therapy with 5 mg once daily. The dose of Rosuvastatin should not exceed 10 mg once daily.
Patients taking lopinavir and ritonavir or atazanavir and ritonavir: Initiate Rosuvastatin therapy with 5 mg once daily. The dose of Rosuvastatin should not exceed 10 mg once daily.
Dosing in Patients with Severe Renal Impairment: For patients with severe renal impairment (Clcr <30 mL/min/1.73m2) not on hemodialysis, dosing of Rosuvastatin should be started at 5 mg once daily and not exceed 10 mg once daily.
10 mg & 20 mg: The patient should be placed on a standard cholesterol-lowering diet before receiving rosuvastatin and should continue on this diet during treatment with Zyrova. Rosuvastatin may be given as a single dose at any time of the day, with or without food. The dose of rosuvastatin should be individualized according to the goal of therapy and patient response.
Usual Recommended Dose: Starting Dosage: 10 mg once daily.
Initiation of therapy with 5 mg once daily may be considered for patients requiring less aggressive LDL-C reductions or who have predisposing factors for myopathy.
Marked Hypercholesterolemia (LDL-C >190 mg/dL) and Aggressive Targets: Starting Dose: 20 mg. The 40-mg dose should be reserved for those patients who have not achieved goal LDL-C at 20 mg. After initiation and/or upon titration of rosuvastatin, lipid levels should be analyzed within 2-4 weeks and dosage adjusted accordingly.
Renal Impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment. For patients with severe renal impairment (CrCl <30 mL/min/m2) not on hemodialysis, dosing of rosuvastatin should be started at 5 mg once daily and not to exceed 10 mg once daily.
In patients taking cyclosporine therapy, therapy should be limited to 5 mg once daily. If rosuvastatin is used in combination with gemfibrozil, the dose should be limited to 10 mg once daily.
40 mg: General Dosing Information: The dose range for Rosuvastatin is 5 to 40 mg orally once daily. The usual starting dose is 10 - 20 mg. Rosuvastatin can be administered as a single dose at any time time of day, with or without food. When initiating Rosuvastatin therapy or switching from another HMG-CoA reductase inhibitor therapy, the appropriate Rosuvastain starting dose should first be utilized, and only then titrated according to the patient's response and individualized goal of therapy.
After initiation or upon titration of Rosuvastatin, lipid levels should be analyzed within 2 to 4 weeks and the dosage adjusted accordingly.
The 40 mg dose of Rosuvastatin should be used only for those patients who have not achieved their LDL-C goal utilizing the 20 mg dose.
Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age): The usual dose range of Rosuvastatin is 5-20 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
Homozygous Familial Hypercholesterolemia: The recommended starting dose of Rosuvastatin is 20 mg once daily. Response to therapy should be estimated from preapheresis LDL-C levels.
Dosing in Asian Patients: In Asian patients, consider initiation of Rosuvastatin therapy with 5 mg once daily due to increased rosuvastatin plasma concentrations. The increased systemic exposure should be taken into consideration when treating Asian patients not adequately controlled at doses up to 20 mg/day.
Use with Concomitant Therapy: Patients taking cyclosporine: The dose of Rosuvastatin should not exceed 5 mg once daily.
Patients taking gemfibrozil: Initiate Rosuvastatin therapy with 5 mg once daily. The dose of Rosuvastatin should not exceed 10 mg once daily.
Patients taking lopinavir and ritonavir or atazanavir and ritonavir: Initiate Rosuvastatin therapy with 5 mg once daily. The dose of Rosuvastatin should not exceed 10 mg once daily.
Dosing in Patients with Severe Renal Impairment: For patients with severe renal impairment (Clcr <30 mL/min/1.73m2) not on hemodialysis, dosing of Rosuvastatin should be started at 5 mg once daily and not exceed 10 mg once daily.
Overdosage
There is no specific treatment for rosuvastatin overdosage. In the event of an overdose, the patient should be treated symptomatically and supportive measures instituted as required. Liver function and CPK levels should be monitored. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance rosuvastatin clearance.
Administration
May be taken with or without food.
Contraindications
5 mg & 40 mg: Rosuvastatin is contraindicated in the following conditions: Patients with known hypersensitivity to any component of this product. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with Rosuvastatin patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels.
Women who are pregnant or may become pregnant. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, Rosuvastatin may cause fetal harm when administered to pregnant women. Additionally, there is no apparent benefit to therapy during pregnancy, and safety in pregnant women has not been established. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued using during pregnancy.
Nursing mothers. Because another drug in this class passes into breastmilk, and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require Rosuvastatin treatment should be advised not to nurse their infants.
10 mg & 20 mg: Hypersensitivity to rosuvastatin or any of the other components of Zyrova. Patients with active liver disease including unexplained persistent elevations of serum transaminases.
Use in Pregnancy & Lactation: Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. Therefore, HMG-CoA reductase inhibitors are contraindicated during pregnancy and in nursing mothers. Women of childbearing potential should use appropriate contraceptive measures.
Women who are pregnant or may become pregnant. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, Rosuvastatin may cause fetal harm when administered to pregnant women. Additionally, there is no apparent benefit to therapy during pregnancy, and safety in pregnant women has not been established. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued using during pregnancy.
Nursing mothers. Because another drug in this class passes into breastmilk, and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require Rosuvastatin treatment should be advised not to nurse their infants.
10 mg & 20 mg: Hypersensitivity to rosuvastatin or any of the other components of Zyrova. Patients with active liver disease including unexplained persistent elevations of serum transaminases.
Use in Pregnancy & Lactation: Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. Therefore, HMG-CoA reductase inhibitors are contraindicated during pregnancy and in nursing mothers. Women of childbearing potential should use appropriate contraceptive measures.
Warnings
Skeletal Muscle Effects: Cases myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin.
These risks can occur at any dose level, but are increased at the highest dose (40 mg).
These risks can occur at any dose level, but are increased at the highest dose (40 mg).
Special Precautions
10 mg & 20 mg: HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. It is recommended that liver function tests be performed prior to and 12 weeks following both the initiation of therapy and any elevation of dose, and periodically thereafter. Should an increase in ALT or AST >3 times the upper limit of normal persist, reduction of dose or withdrawal of rosuvastatin is recommended. Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Rare case of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and with other drug in this class. Myopathy defined as muscle aches or weakness in conjunction with an increase in creatinine phosphokinase (CPK) values, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness. Rosuvastatin therapy should be discontinued if markedly elevated CPK levels >5 times the upper limit of normal occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with rosuvastatin is increased with concurrent administration of other lipid-lowering therapies or cyclosporine. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of this combination. Combination therapy with rosuvastatin and gemfibrozil should generally be avoided. Rosuvastatin therapy should be temporarily withheld in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic endocrine and electrolyte disorders and uncontrolled seizures). Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy eg, renal impairment, advanced age and hypothyroidism.
Before instituting therapy with rosuvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in obese patients and treatment of underlying medical problems.
40 mg: Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g. age > 65 years, inadequately treated hypothyroidism, renal impairment).
The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, or atazanavir/ritonavir. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, co-administered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.
Rosuvastatin therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. Rosuvastatin therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with stain use. IMNM is characterized by : proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation, improvement with immunosuppressive agents.
All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Rosuvastatin.
Liver Enzyme Abnormalities: It is recommended that liver enzyme tests be performed before the initiation of Rosuvastatin, and if signs or symptoms of liver injury occur.
Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to Rosuvastatin therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials.
There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Rosuvastatin, promptly interrupt therapy. If an alternate etiology is not found, do not restart Rosuvastatin.
Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of Rosuvastatin.
Concomitant Coumarin Anticoagulants: Caution should be exercised when anticoagulants are given in conjunction with Rosuvastatin because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.
Proteinuria and Hematuria: In the Rosuvastatin 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 HMG-CoA reductase inhibitors, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, a dose reduction should be considered for patients on Rosuvastatin therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.
Endocrine Effects: Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. Based on clinical trial data with Rosuvastatin, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus. Although clinical studies have shown that Rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if Rosuvastatin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.
Asian Patients: Pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects when compared with Caucasian controls. Rosuvastatin dosage should be adjusted in Asian Patients.
Renal Impairment: Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥30 mL/min/1.73 m2); however, exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment who are not receiving hemodialysis. Rosuvastatin dosing should be adjusted in patients with severe renal impairment (CLcr ≥30mL/min/1.73 m2) not requiring hemodialysis.
Hepatic Impairment: Rosuvastatin is contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Chronic alcohol liver disease is known to increase rosuvastatin exposure; Rosuvastatin should be used with caution in these patients.
Use in Children: 5 mg: The safety and effectiveness of Rosuvastatin in pediatric patients have been established.
10 mg & 20 mg: The safety and efficacy of Zyrova has not been established in children.
40 mg: The safety and effectiveness of Rosuvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia were evaluated in a controlled clinical trial of 12 weeks duration followed by 40 weeks of open-label exposure. Patients treated with 5 mg, 10 mg, and 20 mg daily Rosuvastatin had an adverse experience profile generally similar to that of patients treated with placebo. Although not all adverse reactions identified in the adult population have been observed in clinical trials of children and adolescent patients, the same warnings and precautions for adults should be considered for children and adolescents. There was no detectable effect of Rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in pediatric patients (10 to 17 years of age). Adolescent females should be counseled on appropriate contraceptive methods while on Rosuvastatin therapy. Rosuvastatin has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age. Doses of Rosuvastatin greater than 20 mg have not been studied in the pediatric population.
Use in the Elderly: 5 mg: Elderly patients are higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.
40 mg: Of the 10,275 patients in clinical studies with Rosuvastatin, 3159 (31%) were 65 years and older, and 698 (.8%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients are at higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.
Rare case of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and with other drug in this class. Myopathy defined as muscle aches or weakness in conjunction with an increase in creatinine phosphokinase (CPK) values, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness. Rosuvastatin therapy should be discontinued if markedly elevated CPK levels >5 times the upper limit of normal occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with rosuvastatin is increased with concurrent administration of other lipid-lowering therapies or cyclosporine. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of this combination. Combination therapy with rosuvastatin and gemfibrozil should generally be avoided. Rosuvastatin therapy should be temporarily withheld in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic endocrine and electrolyte disorders and uncontrolled seizures). Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy eg, renal impairment, advanced age and hypothyroidism.
Before instituting therapy with rosuvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in obese patients and treatment of underlying medical problems.
40 mg: Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g. age > 65 years, inadequately treated hypothyroidism, renal impairment).
The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, or atazanavir/ritonavir. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, co-administered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.
Rosuvastatin therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. Rosuvastatin therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with stain use. IMNM is characterized by : proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation, improvement with immunosuppressive agents.
All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Rosuvastatin.
Liver Enzyme Abnormalities: It is recommended that liver enzyme tests be performed before the initiation of Rosuvastatin, and if signs or symptoms of liver injury occur.
Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to Rosuvastatin therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials.
There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Rosuvastatin, promptly interrupt therapy. If an alternate etiology is not found, do not restart Rosuvastatin.
Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of Rosuvastatin.
Concomitant Coumarin Anticoagulants: Caution should be exercised when anticoagulants are given in conjunction with Rosuvastatin because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.
Proteinuria and Hematuria: In the Rosuvastatin 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 HMG-CoA reductase inhibitors, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, a dose reduction should be considered for patients on Rosuvastatin therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.
Endocrine Effects: Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. Based on clinical trial data with Rosuvastatin, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus. Although clinical studies have shown that Rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if Rosuvastatin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.
Asian Patients: Pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects when compared with Caucasian controls. Rosuvastatin dosage should be adjusted in Asian Patients.
Renal Impairment: Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥30 mL/min/1.73 m2); however, exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment who are not receiving hemodialysis. Rosuvastatin dosing should be adjusted in patients with severe renal impairment (CLcr ≥30mL/min/1.73 m2) not requiring hemodialysis.
Hepatic Impairment: Rosuvastatin is contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Chronic alcohol liver disease is known to increase rosuvastatin exposure; Rosuvastatin should be used with caution in these patients.
Use in Children: 5 mg: The safety and effectiveness of Rosuvastatin in pediatric patients have been established.
10 mg & 20 mg: The safety and efficacy of Zyrova has not been established in children.
40 mg: The safety and effectiveness of Rosuvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia were evaluated in a controlled clinical trial of 12 weeks duration followed by 40 weeks of open-label exposure. Patients treated with 5 mg, 10 mg, and 20 mg daily Rosuvastatin had an adverse experience profile generally similar to that of patients treated with placebo. Although not all adverse reactions identified in the adult population have been observed in clinical trials of children and adolescent patients, the same warnings and precautions for adults should be considered for children and adolescents. There was no detectable effect of Rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in pediatric patients (10 to 17 years of age). Adolescent females should be counseled on appropriate contraceptive methods while on Rosuvastatin therapy. Rosuvastatin has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age. Doses of Rosuvastatin greater than 20 mg have not been studied in the pediatric population.
Use in the Elderly: 5 mg: Elderly patients are higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.
40 mg: Of the 10,275 patients in clinical studies with Rosuvastatin, 3159 (31%) were 65 years and older, and 698 (.8%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients are at higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.
Use In Pregnancy & Lactation
5 mg: Rosuvastatin is contraindicated in pregnancy and lactation.
Women of childbearing potential should use appropriate contraceptive measures. Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. Animal studies provide limited evidence of reproductive toxicity. If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.
Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans.
40 mg: Pregnancy: Teratogenic effects: Pregnancy Category X.
Rosuvastatin is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol products, are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hyperlipidemia therapy.
There are no adequate and well-controlled studies of Rosuvastatin in pregnant women. There have been rare reports of congenital anomalies following intrauterine to HMG-CoA reductase inhibitors. In a review of about 100 prospectively followed pregnancies in women exposed to other HMG-CoA reductase inhibitors, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-fourfold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified.
Rosuvastatin crosses the placenta in rats and rabbits. In rats, Rosuvastatin was not teratogenic at systemic exposures equivalent to a human therapeutic dose of 40 mg/day. At 10-12 times the human dose of 40 mg/day, there was decreased pup survival, decreased fetal body weight among female pups, and delayed ossification. In rabbits, pup viability decreased and maternal mortality increased at doses equivalent to the human dose of 40 mg/day.
Rosuvastatin may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking Rosuvastatin, the patient should be apprised of the potential risks to the fetus and the lack of known clinical benefit with continued used during pregnancy.
Nursing Mothers: It is not known whether rosuvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk. In rats, breast milk concentrations of rosuvastatin are three times higher than plasma levels; however, animal breast milk drug levels may not accurately reflect human breast milk levels. Because another drug in this class passes into human milk and because HMG-CoA reductase inhibitors have a potential to cause serious adverse reactions in nursing infants, women who require Rosuvastatin treatment should be advised not to nurse their infants.
Women of childbearing potential should use appropriate contraceptive measures. Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. Animal studies provide limited evidence of reproductive toxicity. If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.
Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans.
40 mg: Pregnancy: Teratogenic effects: Pregnancy Category X.
Rosuvastatin is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol products, are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hyperlipidemia therapy.
There are no adequate and well-controlled studies of Rosuvastatin in pregnant women. There have been rare reports of congenital anomalies following intrauterine to HMG-CoA reductase inhibitors. In a review of about 100 prospectively followed pregnancies in women exposed to other HMG-CoA reductase inhibitors, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-fourfold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified.
Rosuvastatin crosses the placenta in rats and rabbits. In rats, Rosuvastatin was not teratogenic at systemic exposures equivalent to a human therapeutic dose of 40 mg/day. At 10-12 times the human dose of 40 mg/day, there was decreased pup survival, decreased fetal body weight among female pups, and delayed ossification. In rabbits, pup viability decreased and maternal mortality increased at doses equivalent to the human dose of 40 mg/day.
Rosuvastatin may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking Rosuvastatin, the patient should be apprised of the potential risks to the fetus and the lack of known clinical benefit with continued used during pregnancy.
Nursing Mothers: It is not known whether rosuvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk. In rats, breast milk concentrations of rosuvastatin are three times higher than plasma levels; however, animal breast milk drug levels may not accurately reflect human breast milk levels. Because another drug in this class passes into human milk and because HMG-CoA reductase inhibitors have a potential to cause serious adverse reactions in nursing infants, women who require Rosuvastatin treatment should be advised not to nurse their infants.
Adverse Reactions
5 mg: 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; Liver enzyme abnormalities.
In the Rosuvastatin controlled clinical trials database ( placebo or active-controlled) 5.394 patients with a mean treatment durations 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 5.394 patients were; headache, myalgia, abdominal pain, asthenia, nausea.
10 mg & 20 mg: As with other HMG-CoA inhibitors, the incidence of adverse drug reactions tend to be dose-dependent with rosuvastatin. The adverse effects seen are generally mild and transient. Commonly reported adverse effects observed with Zyrova include myalgia, constipation, asthenia, abdominal pain and nausea. Other reported adverse effects include headache, diarrhea, dyspepsia, back pain and flu syndrome. Rare cases of myopathy and rhabdomyolysis have been reported with rosuvastatin. Symptomatic elevation of serum transaminase and CPK levels and occurrence of proteinuria have also been observed with Zyrova.
40 mg: 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).
Liver enzyme abnormalities 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.
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) 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. 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).
In the Rosuvastatin controlled clinical trials database ( placebo or active-controlled) 5.394 patients with a mean treatment durations 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 5.394 patients were; headache, myalgia, abdominal pain, asthenia, nausea.
10 mg & 20 mg: As with other HMG-CoA inhibitors, the incidence of adverse drug reactions tend to be dose-dependent with rosuvastatin. The adverse effects seen are generally mild and transient. Commonly reported adverse effects observed with Zyrova include myalgia, constipation, asthenia, abdominal pain and nausea. Other reported adverse effects include headache, diarrhea, dyspepsia, back pain and flu syndrome. Rare cases of myopathy and rhabdomyolysis have been reported with rosuvastatin. Symptomatic elevation of serum transaminase and CPK levels and occurrence of proteinuria have also been observed with Zyrova.
40 mg: 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).
Liver enzyme abnormalities 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.
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) 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. 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).
Drug Interactions
Cyclosporine: Cyclosporine significantly increased rosuvastatin exposure. Therefore in patients taking cyclosporine, therapy should be limited to Rosuvastatin 5 mg once daily.
Gemfibrozil: Gemfibrozil significantly increased rosuvastatin exposure. Therefore, combination therapy with rosuvastatin and gemfibrozil should be avoided. If used, do not exceed Rosuvastatin 10 mg once daily.
Coumarin Anticoagulants: Rosuvastatin significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with Rosuvastatin. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.
Niacin: The risk of skeletal muscle effects may be enhanced when Rosuvastatin is used in combination with niacin; a reduction in Rosuvastatin dosage should be considered in this setting.
Fenofibrate: When Rosuvastatin was co-administered with fenofibrate no clinically significant increase in the AUC of rosuvastatin of fenofibrate was observed. The benefit of further alterations in lipid levels by the combined use of Rosuvastatin with fibrates should be carefully weighed against the potential risk of this combination.
5 mg: Lopinavir/Ritonavir: The combination of lopinavir and ritonavir significantly increased rosuvastatin exposure. Therefore, in patients taking a combinations of lopinavir and ritonavir, the dose of Rosuvastatin should not be limited to 10 mg once daily. The effect of other protease inhibitors on rosuvastatin pharmacokinetics has not been examined
10 mg & 20 mg: Rosuvastatin levels were increased 7-folds, 2-folds and by 28% when it was administered concomitantly with cyclosporine, gemfibrozil and itraconazole, respectively. Patients on concomitant rosuvastatin and warfarin may have an increase in the International Normalized Ratio (INR). Hence, appropriate monitoring of INR is recommended in such patients. Simultaneous administration of rosuvastatin with an antacid preparation containing albumin and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration by approximately 50%. This effect was mitigated when the antacid was dosed 2 hrs after rosuvastatin. Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC and 31% decrease in Cmax of rosuvastatin. Concomitant use of rosuvastatin and an oral contraceptive resulted in an increase in ethinylestradiol and norgestrel AUC of 26% and 34%, respectively.
40 mg: Protease Inhibitors: Co-administration of rosuvastatin with certain protease inhibitors given in combination with ritonavir has differing effects on rosuvastatin exposure. The protease inhibitor combinations lopinavir/ritonavir and atazanavir/ritonavir increase rosuvastatin exposure. For these combinations the dose of Rosuvastatin should not exceed 10 mg once daily. The combinations of tipranavir/ritonavir or fosamprenavir/ritonavir produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is co-administered with protease inhibitors given in combination with ritonavir.
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, co-administered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.
Gemfibrozil: Gemfibrozil significantly increased rosuvastatin exposure. Therefore, combination therapy with rosuvastatin and gemfibrozil should be avoided. If used, do not exceed Rosuvastatin 10 mg once daily.
Coumarin Anticoagulants: Rosuvastatin significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with Rosuvastatin. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.
Niacin: The risk of skeletal muscle effects may be enhanced when Rosuvastatin is used in combination with niacin; a reduction in Rosuvastatin dosage should be considered in this setting.
Fenofibrate: When Rosuvastatin was co-administered with fenofibrate no clinically significant increase in the AUC of rosuvastatin of fenofibrate was observed. The benefit of further alterations in lipid levels by the combined use of Rosuvastatin with fibrates should be carefully weighed against the potential risk of this combination.
5 mg: Lopinavir/Ritonavir: The combination of lopinavir and ritonavir significantly increased rosuvastatin exposure. Therefore, in patients taking a combinations of lopinavir and ritonavir, the dose of Rosuvastatin should not be limited to 10 mg once daily. The effect of other protease inhibitors on rosuvastatin pharmacokinetics has not been examined
10 mg & 20 mg: Rosuvastatin levels were increased 7-folds, 2-folds and by 28% when it was administered concomitantly with cyclosporine, gemfibrozil and itraconazole, respectively. Patients on concomitant rosuvastatin and warfarin may have an increase in the International Normalized Ratio (INR). Hence, appropriate monitoring of INR is recommended in such patients. Simultaneous administration of rosuvastatin with an antacid preparation containing albumin and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration by approximately 50%. This effect was mitigated when the antacid was dosed 2 hrs after rosuvastatin. Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC and 31% decrease in Cmax of rosuvastatin. Concomitant use of rosuvastatin and an oral contraceptive resulted in an increase in ethinylestradiol and norgestrel AUC of 26% and 34%, respectively.
40 mg: Protease Inhibitors: Co-administration of rosuvastatin with certain protease inhibitors given in combination with ritonavir has differing effects on rosuvastatin exposure. The protease inhibitor combinations lopinavir/ritonavir and atazanavir/ritonavir increase rosuvastatin exposure. For these combinations the dose of Rosuvastatin should not exceed 10 mg once daily. The combinations of tipranavir/ritonavir or fosamprenavir/ritonavir produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is co-administered with protease inhibitors given in combination with ritonavir.
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, co-administered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.
Storage
Store at temperatures not exceeding 30°C.
Keep in cool, dry place. Protect from light.
Keep in cool, dry place. Protect from light.
Action
Pharmacotherapeutic group: HMG-CoA reductase inhibitors.
Pharmacology: Pharmacodynamics: 5 mg: Mechanism of action: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
10 mg and 20 mg: Zyrova contains rosuvastatin calcium which is a new synthetic lipid-lowering agent. Rosuvastatin is a selective competitive inhibitor of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis.
Rosuvastatin is a potent lipid-lowering drug which has been shown to lower the elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, serum triglycerides and ApoB levels. It has also been shown to raise the high-density lipoprotein (HDL)-cholesterol and ApoA-1 levels. Rosuvastatin also lowers the LDL-C/HDL-C, total-C/HDL-C and nonHDL-C/HDL-C and the ApoB/ApoA-1 ratios. A therapeutic effect is obtained within 1 week following treatment initiation and 90% of maximum is achieved in 2 weeks. The maximum response is usually achieved by 4 weeks and is maintained thereafter. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Its primary mechanism for lowering LDL-C is by inhibiting conversion of HMG-CoA to mevalonate, a precursor for cholesterol, in the hepatocyte. Through competitive blockade of HMG-CoA reductase binding to HMG, the rate-limiting enzyme in cholesterol biosynthesis, this agent reduces the production of LDL-C. This in turn, results in up-regulation of LDL-C receptors on the hepatocytes and more rapid clearance of this lipoprotein from plasma.
40 mg: Mechanism of action: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Pharmacokinetics: 5 mg: Absorption: In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%. Administration of rosuvastatin with food did not affect the AUC of rosuvastatin. The AUC of rosuvastatin does not differ following evening or morning drug administration.
Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Elimination: Rosuvastatin is primarily eliminated by excretion in the feces. The elimination half-life of rosuvastatin is approximately 19 hours.
Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of the parent compound. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound.
Excretion: Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.
10 mg & 20 mg: Rosuvastatin achieves peak plasma concentrations in 3-5 hrs after a single dose and exhibits a terminal t½ of approximately 19 hrs. It has a systemic bioavailability of approximately 20%. Systemic exposure of rosuvastatin increases in proportion to dose. It is about 88% bound to plasma proteins, mainly to albumin. Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. It undergoes limited metabolism (approximately 10%), primarily via the cytochrome P-450 CYP2C9 isoenzyme. The major metabolite identified is N-desmethyl rosuvastatin which has approximately 1/6 to ½ the HMG-CoA reductase inhibitory activity of rosuvastatin. Rosuvastatin accounts for >90% of the circulating HMG-CoA reductase inhibitor activity. Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (consisting of absorbed and non-absorbed active substances) and the remaining part is excreted in the urine. Approximately 5% is excreted unchanged in the urine.
40 mg: Rosuvastatin is incompletely absorbed from the gastrointestinal tract, with bioavailability of about 20%. Peak plasma concentrations are achieved about 5 hours after an oral dose. It is taken up extensively by the liver, its primary site of action, and undergoes limited metabolism, mainly by the cytochrome P450 isoenzyme CYP2C9. It is about 90% bound to plasma proteins. The plasma elimination half-life of rosuvastatin is about 19 hours. About 90% of an oral dose of rosuvastatin is excreted in the faeces, including absorbed and nonabsorbed drug, and the remainder is excreted in the urine; about 5% of a dose is excreted unchanged in urine.
Pharmacology: Pharmacodynamics: 5 mg: Mechanism of action: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
10 mg and 20 mg: Zyrova contains rosuvastatin calcium which is a new synthetic lipid-lowering agent. Rosuvastatin is a selective competitive inhibitor of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis.
Rosuvastatin is a potent lipid-lowering drug which has been shown to lower the elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, serum triglycerides and ApoB levels. It has also been shown to raise the high-density lipoprotein (HDL)-cholesterol and ApoA-1 levels. Rosuvastatin also lowers the LDL-C/HDL-C, total-C/HDL-C and nonHDL-C/HDL-C and the ApoB/ApoA-1 ratios. A therapeutic effect is obtained within 1 week following treatment initiation and 90% of maximum is achieved in 2 weeks. The maximum response is usually achieved by 4 weeks and is maintained thereafter. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Its primary mechanism for lowering LDL-C is by inhibiting conversion of HMG-CoA to mevalonate, a precursor for cholesterol, in the hepatocyte. Through competitive blockade of HMG-CoA reductase binding to HMG, the rate-limiting enzyme in cholesterol biosynthesis, this agent reduces the production of LDL-C. This in turn, results in up-regulation of LDL-C receptors on the hepatocytes and more rapid clearance of this lipoprotein from plasma.
40 mg: Mechanism of action: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Pharmacokinetics: 5 mg: Absorption: In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%. Administration of rosuvastatin with food did not affect the AUC of rosuvastatin. The AUC of rosuvastatin does not differ following evening or morning drug administration.
Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Elimination: Rosuvastatin is primarily eliminated by excretion in the feces. The elimination half-life of rosuvastatin is approximately 19 hours.
Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of the parent compound. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound.
Excretion: Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.
10 mg & 20 mg: Rosuvastatin achieves peak plasma concentrations in 3-5 hrs after a single dose and exhibits a terminal t½ of approximately 19 hrs. It has a systemic bioavailability of approximately 20%. Systemic exposure of rosuvastatin increases in proportion to dose. It is about 88% bound to plasma proteins, mainly to albumin. Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. It undergoes limited metabolism (approximately 10%), primarily via the cytochrome P-450 CYP2C9 isoenzyme. The major metabolite identified is N-desmethyl rosuvastatin which has approximately 1/6 to ½ the HMG-CoA reductase inhibitory activity of rosuvastatin. Rosuvastatin accounts for >90% of the circulating HMG-CoA reductase inhibitor activity. Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (consisting of absorbed and non-absorbed active substances) and the remaining part is excreted in the urine. Approximately 5% is excreted unchanged in the urine.
40 mg: Rosuvastatin is incompletely absorbed from the gastrointestinal tract, with bioavailability of about 20%. Peak plasma concentrations are achieved about 5 hours after an oral dose. It is taken up extensively by the liver, its primary site of action, and undergoes limited metabolism, mainly by the cytochrome P450 isoenzyme CYP2C9. It is about 90% bound to plasma proteins. The plasma elimination half-life of rosuvastatin is about 19 hours. About 90% of an oral dose of rosuvastatin is excreted in the faeces, including absorbed and nonabsorbed drug, and the remainder is excreted in the urine; about 5% of a dose is excreted unchanged in urine.
MedsGo Class
Dyslipidaemic Agents
Features
Brand
Zyrova
Full Details
Dosage Strength
10mg
Drug Ingredients
- Rosuvastatin
Drug Packaging
Film-Coated Tablet 100's
Generic Name
Rosuvastatin Calcium
Dosage Form
Film-Coated Tablet
Registration Number
DRP-10291
Drug Classification
Prescription Drug (RX)