Rosucres-10/Rosucres-20

10 mg: Pink, round, biconvex, beveled edge, film-coated tablet, debossed with 'R10' on one side and plain on the other side.
Each film-coated tablet contains Rosuvastatin Calcium Ph. Eur. equivalent to Rosuvastatin 10 mg.
20 mg: Pink, round, biconvex, film-coated tablet, debossed with 'R20' on one side and plain on the other side.
Each film-coated tablet contains Rosuvastatin Calcium Ph. Eur. equivalent to Rosuvastatin 20 mg.
Excipients: q.s.

Pharmacology: Pharmacokinetics: 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.

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 Familial 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.

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 of day, with or without food. When initiating Rosuvastatin therapy or switching from another HMG-CoA reductase inhibitor therapy, the appropriate Rosuvastatin 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 pre-apheresis 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/1.73 m²) not on hemodialysis, dosing of Rosuvastatin should be started at 5 mg once daily and not exceed 10 mg once daily.

There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required.
Hemodialysis does not significantly enhance clearance of Rosuvastatin.

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 mother. Because another drug in this class passes into breast milk, 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.

Skeletal Muscle Effects: Cases of 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).
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, coadministered 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.
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 >30 mL/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.
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.
Use in Children: 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 prepubertal 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: 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.

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.

The following serious adverse reactions are discussed in greater detail in other sections of the monograph: 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 post approval 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 no 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).

Cyclosporine: Cyclosporine increased rosuvastatin exposure. Therefore, in patients taking cyclosporine, the dose of Rosuvastatin should not exceed 5 mg once daily.
Gemfibrozil: Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with Rosuvastatin and gemfibrozil should be avoided. If used together, the dose of Rosuvastatin should not exceed 10 mg once daily.
Protease Inhibitors: Coadministration 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.
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 lipid modifying doses (>1 g/day) of niacin; caution should be used when prescribing with Rosuvastatin.
Fenofibrate: When Rosuvastatin was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with Rosuvastatin.
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, coadministered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.

Store at temperatures not exceeding 30°C.

Dyslipidaemic Agents

C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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