Cholestor

Cholestor

rosuvastatin

Manufacturer:

MacroPhar

Distributor:

MacroPhar Lab
Full Prescribing Info
Contents
Rosuvastatin Ca.
Description
Cholestor 10: Rosuvastatin calcium equivalent to Rosuvastatin 10 mg.
Action
Pharmacology: Mechanism of Action: Rosuvastatin calcium is a synthetic heptenoic acid-derivative antilipemic agent. The drug is a selective, competitive inhibitor of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate (an early and rate-limiting step in cholesterol biosynthesis). Rosuvastatin reduces total and low density lipoprotein(LDL)-cholesterol, and triglyceride concentrations, and increases HDL-cholesterol concentrations in patients with primary hyperlipidemia or mixed dyslipidemia. Rosuvastatin also reduces triglyceride concentrations in patients with primary hypertriglyceridemia.
Pharmacodynamics: Inhibit HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.
Pharmacokinetics: Absorption: The absolute bioavailability of rosuvastatin is approximately 20%. Peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing.
Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88% primarily bound to plasma proteins, mostly albumin.
Metabolism: Rosuvastatin is metabolized by cytochrome P450 2C9. Approximately 10 % of radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of Rosuvastatin.
Excretion: Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). The elimination half-life (t1/2) of rosuvastatin is approximately 19 hours.
Indications/Uses
Dyslipidemias: Rosuvastatin is used as an adjunct to dietary therapy in the management of primary hypercholesterolemia and mixed dyslipidemia. Rosuvastatin is also used in the management of hypertriglyceridemia. The efficacy of rosuvastatin in patients with Frederickson type I, III, or V dyslipidemia has not been established. Nondrug therapies and measures specific for the type of hyperlipoproteinemia (therapeutic lifestyle changes) are the initial treatments of choice, including dietary management (e.g., restriction of saturated fat and cholesterol intake, addition of plant stanol/sterols and viscous fiber to diet), weight control, an appropriate program of physical activity, and management of potentially contributory disease. Drug therapy is not a substitute for but an adjunct to these nondrug therapies and measures, which should be continued when drug therapy is initiated.
Primary Hypercholesterolemia and Mixed Dyslipidemia: Rosuvastatin is used as an adjunct to dietary therapy to reduce elevated total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), non-high-density (non-HDL)-cholesterol, and triglyceride concentrations and to increase HDL-cholesterol in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. Rosuvastatin alone or combined with extended-release niacin improves the atherogenic lipid profile in patients with mixed dyslipidemia and low HDL-cholesterol concentrations.
Homozygous Familial Hypercholesterolemia: Rosuvastatin also is used to reduce elevated serum total cholesterol and LDL-cholesterol and apo B concentrations in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or if such treatments are unavailable.
Hypertriglyceridemia: Rosuvastatin is used as an adjunct to diet in the treatment of patients with elevated triglyceride concentrations (Fredrickson type IV).
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 high sensitivity C-reactive protein (hsCRP) level, age, hypertension, low HDL-Cholesterol, smoking or family history of premature coronary heart disease, Rosuvastatin is indicated to reduce total mortality and the risk of major cardiovascular events (cardiovascular death, stroke, myocardial infarction, unstable angina, or arterial revas-cularization).
Dosage/Direction for Use
Dosage: Dosage of rosuvastatin calcium is expressed in terms of rosuvastatin. Before treatment initiation the patient should be placed on a standard choleterol-lowering diet that should continue during treatment. The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.
Primary Hypercholesterolemia (Heterozygous Familial and Non-familial) and Mixed Dyslipidemia: The usual initial dosage of rosuvastatin in adults is 10 mg once daily given without regard to meals. Initiation of therapy with 5 mg once daily may be considered for patients requiring less aggressive LDL-cholesterol reductions or for those who have predisposing factors for myopathy. For patients with marked hypercholesterolemia (LDL-cholesterol exceeding 190 mg/dL) and aggressive lipid targets, an initial rosuvastatin dosage of 20 mg once daily may be considered. Dosage may be increased as necessary to a maximum recommended dosage of 40 mg daily. The 40-mg daily dosage of rosuvastatin should be reserved for those patients who have not achieved their LDL-cholesterol goal with the 20-mg daily dosage.
Homozygous Familial Hypercholesterolemia: The usual initial dosage of rosuvastatin in adults with homozygous familial hypercholesterolemia is 20 mg once daily; the maximum recommended dosage is 40 mg once daily. Rosuvastatin should be used in these patients as an adjunct to other lipid lowering treatments (e.g., LDL-cholesterol apheresis) or if such treatments are unavailable. Response to therapy in patients undergoing LDL-apheresis should be estimated based on per-apheresis LDL-cholesterol levels.
Hypertriglyceridemia: The usual initial dosage of rosuvastatin in adults with hypertriglyceridemia is 10 mg once daily; the usual dosage range is 5-40 mg daily. The recommended maximum dosage of rosuvastatin in patients with hypertriglyceridemia is 40 mg once daily and should be reserved for patients responding inadequately to the 20-mg daily dosage.
Prevention of Cardiovascular Events: The recommended start dose is 5 or 10 mg once daily in both statin naive patients or patients switched from another HMG-CoA reductase inhibitor. The choice of starting dose should take into account the individual patients cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. A dose adjustment to 20 mg can be made after 2 to 4 weeks, if necessary.
Special Populations: Renal Impairment: No modification of dosage is necessary for patients with mild to moderate renal insufficiency. In patients with severe renal impairment (creatinine clearance less than 30 mL/minute per 1.73 m2) who are not undergoing hemodialysis, rosuvastatin should be initiated at a dose of 5 mg once daily and dosage should not exceed 10 mg once daily.
Pediatric Use: Safety and efficacy not established in prepubertal children or in children younger than 10 years of age; however, a few patients 8 years of age or older with homozygous familial hypercholesterolemia have been treated with the drug. Adolescent girls should be advised to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.
Geriatric Use: Mean reductions in LDL-cholesterol concentrations were slightly higher in geriatric patients (65 years of age and older) than in younger patients. However, no clinically relevant differences in laboratory abnormalities or rates of drug discontinuance were reported. Risk of myopathy is increased in patients (particularly women) of advanced age (65 years of age or older) and in those with small body frame and frailty; use with caution in such patients.
Mode of Administration: Administered orally at any time of day, with or without food.
Overdosage
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.
Haemodialysis does not significantly enhance the clearance of Rosuvastatin.
Contraindications
Patients with known hypersensitivity to rosuvastatin or any ingredient in the formulation.
Patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.
Use in Pregnancy & Lactation: All statins are contraindicated in pregnant or nursing women.
Warnings
It is contraindicated in pregnant or nursing women.
It is contraindicated in patients with hepatic impairments.
If muscle pain of calf, back or entire body occur during the administration of rosuvastatin, the drug should be discontinued and consult a physician.
The liver function tests should be performed before and at 6 and 12 weeks after initiation of rosuvastatin therapy and periodically (e.g., semiannually) thereafter. If increases in AST or ALT concentrations of 3 times the upper limit of normal or higher persist, the dosage of rosuvastatin should be discontinued and consult a physician.
Caution should be exercised when digoxin, warfarin are given in conjunction with rosuvastatin as the serum concentration of these drugs may be enhanced by concomitant administration of rosuvastatin.
The risk of myopathy and rhabdomyolysis may be increased in patients receiving rosuvastatin concomitant with certain drugs, including certain azole antifungals (e.g. ketoconazole, itraconazole), macrolide antibiotics (e.g. erythromycin, clarithromycin), HIV protease inhibitors (e.g. indinavir, ritonavir, nelfinavir, saquinavir), verapamil, diltiazem, gemfibrozil, nicotinic acid, cyclosporine and amiodarone.
The risk of rhabdomyolysis may be increased in certain groups of patients' e.g. geriatric patient, the patient with liver or renal functional impairment, the patient with chronic alcoholism, hypothyroidism or using high dose.
Caution should be exercised when colchicine is given, especially in the elderly or patients with renal impairment.This combination will increase the risk of myopathy or rhabdomyolysis.
This medicine may cause the risk of hyperglycemia.
Special Precautions
Fetal/Neonatal Morbidity and Mortality: Suppression of cholesterol biosynthesis could cause fetal harm. Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.
Hepatic Effects: Therapy with rosuvastatin and other statins has been associated with increases in serum aminotransferase (transaminase) concentrations (i.e., AST [SGOT], ALT [SGPT]). Therefore, the liver function tests be performed before and at 12 weeks after initiation of rosuvastatin therapy or any increase in dosage and periodically (e.g., semiannually) thereafter. Patients who develop increased serum transaminase concentrations or manifestations of liver disease should have frequent liver function tests performed thereafter until the abnormalities return to normal. If increases in AST or ALT concentrations of 3 times the upper limit of normal or higher persist, the dosage of rosuvastatin should be reduced or the drug discontinued. Jaundice has been reported rarely with rosuvastatin therapy.
Musculoskeletal Effects: Myopathy (manifested as muscle pain, tenderness, or weakness and increases in serum creatinine kinase [CK] concentration exceeding 10 times the upper limit of normal) has been reported occasionally (up to 0.1%) with rosuvastatin therapy. Rhabdomyolysis (characterized by musce pain or weakness with marked increases [exceeding 10 times the upper limit of normal] in serum CK concentrations and increases in serum creatinine concentrations [usually accompanied by brown urine and urinary myoglobinuria]) with or without acute renal failure secondary to myoglobinuria has been reported rarely with statin therapy, including with rosuvastatin. Rhabdomyolysis occurs more frequently in patients receiving rosuvastatin 40 mg daily compared with lower dosages. However, it does not appear that the risk of rhabdomyolysis is greater with rosuvastatin than with other statins. In clinical studies, the incidence of myopathy and rhabdomyolysis increased in patients receiving rosuvastatin dosages exceeding the recommended dosage range of 5-40 mg daily. Risk of myopathy may be increased in patients with predisposing factors for myopathy (e.g., advanced age [65 years or older, particularly women], hypothyroidism), patients receiving rosuvastatin dosages exceeding the recommended dosage range of 5-40 mg daily, and patients at risk of increased exposure to rosuvastatin (e.g., Asian patients, patients with renal impairment). Risk also may be increased by concomitant use of certain drugs, including cyclosporine, niacin, fibric-acid derivatives, macrolide antibiotics (e.g. erythromycin), certain azole antifungals, and alcohol. Use of rosuvastatin with fibric acid derivatives or niacin should be carefully weighed against the potential risks of this combination; combination therapy with gemfibrozil generally should be avoided. Discontinue rosuvastatin if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected. Temporarily withhold therapy in any patient experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of acute renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery;trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).
Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.
Asian Population Pharmacokinetic studies, including a large study conducted in the US, show an approximate two-fold elevation in median exposure to rosuvastatin (peak plasma concentration and AUC) in Asian patients (of Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian ancestry) compared with Caucasian patients. This increase should be considered when deciding upon rosuvastatin dosage in Asian patients.
Renal Effects: Transient dipstick-positive proteinuria and microscopic hematuria (not associated with worsening renal function) have been reported in patients receiving rosuvastatin. These findings occurred predominantly in patients receiving higher than recommended dosages (i.e., 80 mg), but were more frequent in patients receiving rosuvastatin 40 mg compared with lower doses of rosuvastatin or comparator statins in clinical trials. Although the clinical importance of this finding is not known, dosage reduction should be considered for patients receiving 40 mg of rosuvastatin daily who have unexplained persistent proteinuria during routine urinalysis testing.
Endocrine Effects: Although clinical studies have shown that rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, statins interfere with cholesterol synthesis and theoretically may blunt adrenal or gonadal steroid hormone production. Caution should be exercised if any statin, including rosuvastatin, or other agent used to lower cholesterol levels is used concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones (e.g., ketoconazole, spironolactone, cimetidine).
Use In Pregnancy & Lactation
Use in pregnancy: Pregnancy Category X.
Rosuvastatin is contraindicated during pregnancy. If Rosuvastatin is administered to a woman with reproductive potential, she should be apprised of the potential hazard to the fetus. Rosuvastatin crosses the placenta. It is believed that HMG-CoA reductase inhibitors may decrease biologically active substances active substances derived from cholesterol and may cause fetal harm.
Lactation: Distributed into milk in animals; not known whether rosuvastatin is distributed into milk in humans. Discontinue nursing or drug, taking into account the importance of the woman.
Adverse Reactions
The most frequent adverse effects thought to be related to rosuvastatin include myalgia, constipation, asthenia, abdominal pain, and nausea. Adverse effects reported without attribution of causality in at least 2% of patients receiving rosuvastatin include pharyngitis, headache, diarrhea, dyspepsia, nausea, myalgia, asthenia, back pain, flu syndrome, urinary tract infection, rhinitis, and sinusitis.
Drug Interactions
Antacids: Potential pharmacokinetic interaction (decreased plasma rosuvastatin concentrations with concomitant aluminum-magnesium hydroxide antacid). Administer antacids 2 hours after rosuvastatin.
Bile Acid Sequestrants: Potential pharmacodynamic interaction (enhanced effect on total and LDL-cholesterol) with concomitant bile acid sequestrant.
Cyclosporine: Potential pharmacokinetic interaction (clinically important increases in peak plasma rosuvastatin concentration and AUC with concomitant cyclosporine); limit dosage of rosuvastatin to 5 mg daily with such concomitant therapy.
Digoxin: Pharmacokinetic interaction unlikely (no change in plasma digoxin concentrations with concomitant rosuvastatin).
Drugs Affecting Hepatic Microsomal Enzymes: Pharmacokinetic interaction unlikely (rosuvastatin clearance not dependent on metabolism by cytochrome P-450 isoenzyme 3A4). Interactions (e.g., increases or decreases in AUC of rosuvastatin) between rosuvastatin and ketoconazole, erythromycin, itraconazole, or fluconazole not deemed clinically important.
Fenofibrate: Pharmacokinetic interaction unlikely (no changes in rosuvastatin or fenofibrate plasma concentrations with concomitant administration).
Gemfibrozil: Increased risk of adverse musculoskeletal effects (i.e., increased CK, myoglobinuria, rhabdomyolysis) with concomitant use. Avoid concomitant use unless potential benefit outweighs risk.
Oral Contraceptives: Potential pharmacokinetic interaction (increased plasma concentrations of ethinyl estradiol and norgestrel) with concomitant rosuvastatin.
Warfarin: Potential pharmacodynamic interaction (clinically important increase in international normalized ratio [INR]) when rosuvastatin (40 mg) given concomitantly with warfarin (25 mg); plasma warfarin concentrations unchanged. Determine INR prior to initiating rosuvastatin and following any change in dosage and then frequently enough thereafter until stable INR is documented, then at usually recommended intervals.
Storage
Keep in tight containers, Store below 30°C.
ATC Classification
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
Presentation/Packing
Tab 10 mg (pink, round, biconvex, with "MCP 10" engraved on one side and plain on the other side) x 3 x 10's. 20 mg x 3 x 10's.
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