Auritz also contains the following inactive ingredients: Tribasic calcium phosphate, microcrystalline cellulose (PH 102), butylated hydroxy toluene, povidone K-30, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Instacoat universal white IH, purified water; color: Titanium dioxide.
Auritz is a synthetic lipid-lowering agent for oral administration. The chemical name for rosuvastatin calcium is bis[(E)-7-[4(4-fluorophenyl)-6-isopropyl 2[methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5-dihydroxyhept-6-enoic acid] calcium salt. The empirical formula is (C22H27FN3O6S)2Ca and the molecular weight is 1001.14.
Pharmacology: 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 of cholesterol. Rosuvastatin produces its lipid-modifying effects in 2 ways. First, it increases the number of hepatic low-density lipoprotein (LDL) receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, rosuvastatin inhibits hepatic synthesis of very low-density lipoprotein (VLDL), which reduces the total number of VLDL and LDL particles.
Pharmacokinetics: Absorption: In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3-5 hrs following oral dosing. Both Cmax and area under the curve (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 L. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
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 1/6 to 1/2 the HMG-CoA reductase inhibitory activity of the parent compound. Overall, >90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound.
Excretion: Following oral administration, rosuvastatin and its metabolite are primarily excreted in the feces (90%). The elimination half-life (t½) of rosuvastatin is approximately 19 hrs. After an intravenous dose, approximately 28% of total body clearance was via the renal route and 72% by the hepatic route.
Hyperlipidemia and Mixed Dyslipidemia: Rosuvastatin is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, non-HDL-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 10-17 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 1 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 or premature cardiovascular disease (CVD) or 2 or more other CVD risk factors.
Hypertriglyceridemia: Rosuvastatin is indicated as 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 (eg, 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.
Limitations of Use: The effect of rosuvastatin on cardiovascular morbidity and mortality has not been determined.
Rosuvastatin has not been studied on Fredrickson Type I and V dyslipidemias.
General Dosing Information: The dose range for rosuvastatin is 5-40 mg orally once daily.
Rosuvastatin can be administered as a single dose at any time of the 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.
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.
Hyperlipidemia, Mixed Dyslipidemia, Hypertriglyceridemia, Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) and Slowing of the Progression of Atherosclerosis: The recommended starting dose of rosuvastatin is 10 mg dose once daily. For patients with marked hyperlipidemia (LDL-C >190 mg/dL) and aggressive lipid targets, a 20 mg starting dose may be considered.
After initiation or upon titration of rosuvastatin, lipid levels should be analyzed within 2-4 weeks and the dosage adjusted accordingly.
Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years): The usual dose range of rosuvastatin is 5-20 mg/day; the maximum recommended dose is 20 mg/day (doses >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.
Homozygous Familial Hypercholesterolemia: The recommended starting dose of rosuvastatin is 20 mg once daily. Response to therapy should be estimated from pre-aphereses LDL-C levels.
Dosage in Asian Patients: Initiation of rosuvastatin therapy with 5 mg once daily should be considered for Asian patients.
Use with Cyclosporine or Lopinavir/Ritonavir: In patients taking cyclosporine, the dose of rosuvastatin should be limited to 5 mg once daily. In patients taking a combination of lopinavir and ritonavir, the dose of rosuvastatin should be limited to 10 mg once daily.
Concomitant Lipid-Lowering Therapy: The risk of skeletal muscle effects may be enhanced when rosuvastatin is used in combination with niacin or fenofibrate; a reduction in rosuvastatin is used in combination with gemfibrozil, the dose of rosuvastatin should be limited to 10 mg daily.
Dosage in Patients with Severe Renal Impairment: For patients with severe renal impairment (CrCl <30 mL/min/1.73 m2) not on hemodialysis, dosing of rosuvastatin should be started at 5 mg once daily and should 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.
However, no specific symptoms of an overdose have been reported.
Patients with known hypersensitivity to any component of Auritz. 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.
Use in pregnancy: 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 pregnancy women. There have been rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors.
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 use during pregnancy.
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 Auritz, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued use during pregnancy.
Use in lactation: 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.
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.
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.
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 or lopinavir/ritonavir.
Rosuvastatin should be discontinued if markedly elevated creatinine 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 (eg, sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures). All patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Liver Enzyme Abnormalities and Monitoring: It is recommended that liver enzyme tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (eg, semiannually) thereafter.
Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG-CoA reductase inhibitors, including rosuvastatin.
Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved. Should an increase in ALT or AST of >3 times ULN 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 chronic liver disease.
Proteinuria and Hematuria: 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: Rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, however, caution should be exercised if rosuvastatin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones eg, ketoconazole, spironolactone and cimetidine.
Renal Impairment: Rosuvastatin exposure is not influenced by mild to moderate renal impairment; 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 not requiring hemodialysis and clinical pharmacology.
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.
Effects on the Ability to Drive or Operate Machinery: Studies to determine the effect of rosuvastatin on the ability to drive and use machines have not been conducted. However, based on its pharmacodynamic properties, rosuvastatin is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.
Use in children: 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. Doses of rosuvastatin >20 mg have not been studied in the pediatric population.
Use in the elderly: Elderly patients are at higher risk of myopathy and rosuvastatin should be prescribed with caution in the elderly use.
Use in pregnancy: 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 pregnancy women. There have been rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors.
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 use during pregnancy.
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 Auritz, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued use during pregnancy.
Use in lactation: 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. 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 (see Precautions): Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis); liver enzyme abnormalities.
The most commonly reported adverse reactions with rosuvastatin: Headache; myalgia; abdominal pain; asthenia; nausea.
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.
Lopinavir/Ritonavir: The combination of lopinavir and ritonavir significantly increased exposure. Therefore, in patients taking a combination of lopinavir and ritonavir, the dose of rosuvastatin should be limited to 10 mg once daily. The effect of the other protease inhibitors on rosuvastatin pharmacokinetics has not been examined.
Coumarin Anticoagulants: Rosuvastatin significantly increased International Normalized Ratio (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 or 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 risks of this combination.
Store below 25°C in a dry place. Protect from light and moisture.
Shelf-Life: 24 months.
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
FC tab (round, biconvex, white-colored, smooth with a plain surface on both sides) 10 mg x 3 x 10's. 20 mg x 3 x 10's.
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