Rosustat

Rosuvastatin calcium.

Each film-coated tablet contains: Rosuvastatin (as calcium) 10 mg and 20 mg.

Pharmacology: Rosuvastatin is a hypolipidaemic agent; it is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-determining enzyme for cholesterol synthesis. HMG-CoA reductase inhibitors (sometimes called "statins") reduce total cholesterol, low-density lipoprotein (LDL)-cholesterol and very-low-density lipoprotein (VLDL)-cholesterol concentrations in plasma. They also tend to reduce triglycerides and to increase high-density lipoprotein (HDL)-cholesterol concentrations. They are considered to exert their hypocholesterolaemic action by stimulating an increase in LDL-receptors on hepatocyte membranes thereby increasing the clearance of LDL from the circulation.
Pharmacokinetics: Rosuvastatin is administered orally in the active form with peak plasma levels occurring 5 hours after dosing. Exposure increases linearly over the dose range. The half life is 19 hours and does not increase with increasing dose. Absolute bioavailability is 20%. There is minimal accumulation on repeated once daily dosing.
Rosuvastatin undergoes first pass extraction in the liver, which is the primary site of cholesterol synthesis and LDL-C clearance. Rosuvastatin is approximately 90% bound to plasma proteins, mostly albumin. The parent compound, accounts for greater than 90% of the circulating active HMG CoA reductase inhibitor activity.
Rosuvastatin undergoes limited metabolism (approximately 10%), mainly to the N-desmethyl form, and 90% is eliminated as unchanged drug in the feces with the remainder being excreted in the urine.

Rosuvastatin should be used as an adjunct to diet when the response to diet and exercise is inadequate.
Prevention of Cardiovascular Events: In adult patients with an increased risk of atherosclerotic cardiovascular disease based on the presence of cardiovascular disease risk markers such as an elevated hsCRP level, age, hypertension, low HDL-C, smoking or a family history of premature coronary heart disease, Rosuvastatin is indicated to reduce total mortality and the risk of major cardiovascular events (cardiovascular death, stroke, MI, unstable angina, or arterial revascularization).
In adult patients with hypercholesterolemia: Rosuvastatin is indicated to: reduce elevated LDL-C, Total Cholesterol, triglycerides and to increase HDL-cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non familial) and mixed dyslipidaemia (Fredrickson Types IIa and IIb). Rosuvastatin also lowers ApoB, nonHDL-C, VLDL-C, VLDL-TG, the LDL-C/HDL-C, total C/HDL-C, nonHDL-C/HDL-C, ApoB/ApoA-1 ratios and increases ApoA-I in these populations.
Treat patients with primary dysbetalipoproteinaemia (Fredrickson Type III hyperlipoproteinaemia).
Treat isolated hypertriglyceridaemia Fredrickson Type IV hyperlipidemia.
Reduce Total Cholesterol and LDL-C in patients with homozygous familial hypercholesterolaemia, as an adjunct to diet and other lipid lowering treatments (e.g LDL apheresis) or alone if such treatments are unavailable.
Slow or delay the progression of atherosclerosis.
Children and adolescents 10 to 17 years of age: Rosuvastatin is indicated to reduce the Total Cholesterol, LDL-C and Apo B in patients with heterozygous familial hypercholesterolemia (HeFH).

Rosuvastatin is given in an initial dose of 5 to 10 mg once daily, at night, depending on plasma-cholesterol concentrations, cardiovascular risk factors, and risk factor for adverse effects, or as prescribed by the physician. The maintenance dose ranges from 5 to 40 mg once daily, although the 40-mg dose is reserved for patients with high cardiovascular risk who do not achieve their target cholesterol concentration at lower doses and who do not have risk factors for adverse effects.

Rosuvastatin is contraindicated in patients with active liver disease, including unexplained, persistent elevations of hepatic aminotransferases. It is also contraindicated in pregnant patients as suppression of cholesterol biosynthesis could cause fetal harm.

Rosuvastatin should not be given to patients with acute liver disease or unexplained persistent raised serum-aminotransferase concentrations. It should be avoided during pregnancy since there is a possibility that it could interfere with fetal sterol synthesis; there have been a few reports of congenital abnormalities associate with HMG-CoA reductase inhibitors. It should be discontinued if marked increases in serum-aminotransferase or creatinine-phosphokinase concentrations occur.

Rosuvastatin is generally well tolerated. The adverse events seen with Rosuvastatin are generally mild and transient. In controlled clinical trials less than 4% of Rosuvastatin treated patients were withdrawn due to adverse events. This withdrawal rate was comparable to that reported in patients receiving placebo.
Common (≥1/100, <1/10): Headache, myalgia, asthenia, constipation, dizziness, nausea, abdominal pain.
Uncommon (≥1/1000, <1/100): Pruritus, rash and urticaria.
Rare (≥1/10,000, <1/1000): Myopathy (including myositis), hypersensitivity reactions (including angioedema), rhabdomyolysis, pancreatitis.
As with other HMO CoA reductase inhibitors, the incidence of adverse drug reactions tends to increase with increasing dose.
Skeletal Muscle Effects: Rare cases of rhabdomyolysis, which were occasionally associated with impairment of renal function, have been reported with rosuvastatin and with other marketed statins.
Laboratory Effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in liver transaminases and CK has been observed in a small number of patients taking rosuvastatin. Abnormal urinalysis testing (dipstick-positive proteinuria) has been seen in a small number of patients taking Rosuvastatin and other HMG-CoA reductase inhibitors. The protein detected was mostly tubular in origin. In most cases, proteinuria deceases or disappears spontaneously on continued therapy, and is not predictive of acute or progressive renal disease.
Other Effects: In a long-term controlled clinical trial Rosuvastatin was shown to have no harmful effects on the ocular lens. In Rosuvastatin treated patients, there was no impairment of adrenocortical function.
Post Marketing Experience: In addition to the previously mentioned, the following adverse events have been reported during post marketing experience for Rosuvastatin: Musculoskeletal disorders: Very rare: Arthralgia.
As with other HMG-CoA reductase inhibitors, the reporting rate for the rhabdomyolysis in post-marketing use is higher at the highest marketed dose.
Hepatobiliary disorders: Very rare: jaundice, hepatitis; rare: increased hepatic transaminases.
Nervous system disorder: Very rare: memory loss.
Children and adolescents 10 to 17 years of age: The safety profile of Rosuvastatin is similar in children or adolescent patients and adults although CK elevations >10 x ULN and muscle symptoms following exercise or increased physical activity, which resolved with continued treatment, were observed more frequently in clinical trials of children and adolescents. However, the same special warnings and special precautions for use in adults also apply to children and adolescents.

The most serious consequence of drug interactions with rosuvastatin and other statins is the development of myopathy or rhabdomyolysis. Drugs that can cause myopathy when given alone increase the risk of myopathy with all statins; these drugs include fibric acid derivatives (fibrates or gemfibrozil), and nicotinic acid. Rosuvastatin undergoes limited metabolism, principally by the cytochrome P450 isoenzyme CYP2C9, and may not have the same interactions with enzyme inhibitors as simvastatin. However, increased plasma-rosuvastatin concentrations have been reported with ciclosporin, HIV-protease inhibitors, and to a lesser extent, with gemfibrozil, and such combinations should be avoided. If they must be given together, lower doses of rosuvastatin should be used.

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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