Lipidar

Yellow colored, round shaped, biconvex film-coated tablet with break line on one side and plain on the other side.
Each film-coated tablet contains: Rosuvastatin (as calcium), USP 40 mg.
Excipients with known effect: This product contains: Lactose. If the patient has been told by their doctor that they have an intolerance to some sugars, they should contact their doctor before taking this medicinal product. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium benzoate (E 211). This medicine contains 2.00 mg of sodium benzoate in each 100 mg tablet. Sodium benzoate may increase jaundice (yellowing of the skin and the eyes) in newborn babies (up to 4 weeks old).

Lipid Modifying Agent (HMG-CoA Reductase Inhibitor).
Pharmacology: 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: Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours after oral administration. The absolute bioavailability is approximately 20%. Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin. Rosuvastatin undergoes limited metabolism (approximately 10%). The main metabolites identified are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin whereas the lactone form is considered clinically inactive. Rosuvastatin accounts for greater than 90% of the circulating HMG-CoA reductase inhibitor activity. Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces and the remaining part is excreted in urine. Approximately 5% is excreted unchanged in urine. As with other HMG-CoA reductase inhibitors, the hepatic uptake of rosuvastatin involves the membrane transporter OATP-C. This transporter is important in the hepatic elimination of rosuvastatin.

Treatment of hypercholesterolemia: Adults, adolescents and children aged 10 years or older with primary hypercholesterolemia (type IIa including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.
Homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.
Prevention of cardiovascular events: Prevention of major cardiovascular events in patients who are estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors.

Before treatment initiation, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualized according to the goal of therapy and patient response, using current consensus guidelines.
Rosuvastatin may be given at any time of day, with or without food.
Treatment of hypercholesterolemia: Recommended start dose: 5 or 10 mg orally once daily in both statin naïve or patients switched from another HMG-CoA reductase inhibitor.
A dose adjustment to the next dose level can be made after 4 weeks, if necessary.
Prevention of cardiovascular events: Recommended start dose: 20 mg daily.

Specific treatment is not available for rosuvastatin overdose. Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted, as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive binding to plasma proteins, hemodialysis is not expected to significantly enhance rosuvastatin clearance.

Hypersensitivity to rosuvastatin or to any of the excipients; Active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3x the upper limit of normal (ULN); Severe renal impairment (creatinine clearance <30 mL/min); Myopathy; Concomitant ciclosporin; Pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.

Skeletal muscle effects (e.g. myopathy and rhabdomyolysis): Risks increase when higher doses are used concomitantly with cyclosporine and strong CYP 3A4 inhibitors (e.g. clarithromycin, itraconazole, human immunodeficiency virus (HIV) or hepatitis C virus (HCV) protease inhibitors). Predisposing factors include advanced age (>65), uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. Patients are advised to promptly report to their physician any unexplained and/or persistent muscle pain, tenderness, or weakness. The use of Rosuvastatin should be discontinued if myopathy is diagnosed or suspected.
Creatine kinase measurement: Creatine kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline (>5xULN) a confirmatory test should be carried out within 5-7 days. If the repeat test confirms a baseline CK >5xULN, treatment should not be started.
Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter.

Pregnancy Category X. Rosuvastatin is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid-lowering drugs 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 a pregnant woman. The use of Rosuvastatin should be discontinued as soon as pregnancy is recognized.
Rosuvastatin use is contraindicated during breastfeeding. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. It is not known whether Rosuvastatin is present in human milk, but it has been shown that another drug in this class passes into human milk and Rosuvastatin is present in rat milk. Because of the potential for serious adverse reactions in a breastfed infant, women should be advised that breastfeeding is not recommended during treatment with Rosuvastatin.

See table.

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Transporter protein inhibitors: Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of rosuvastatin with medicinal products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy.
Ciclosporin: During concomitant treatment with rosuvastatin and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers. Rosuvastatin is contraindicated in patients receiving concomitant ciclosporin.
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure. The concomitant use of rosuvastatin and some protease inhibitor combinations may be considered after careful consideration of rosuvastatin dose adjustments.
Gemfibrozil and other lipid-lowering products: Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses (≥1 g/day) of niacin increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone.
Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of CYP450 isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. Therefore, drug interactions resulting from CYP450-mediated metabolism are not expected. No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).
Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of rosuvastatin in patients treated concomitantly with vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant) may result in an increase in INR. Discontinuation or down-titration of rosuvastatin may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.
Fusidic acid: As with other statins, muscle-related events, including rhabdomyolysis, have been reported in post-marketing experience with rosuvastatin and fusidic acid given concurrently.

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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