Rosubolic-10

Rosubolic-10

rosuvastatin

Manufacturer:

Innova Captab

Distributor:

Ambica
Full Prescribing Info
Contents
Rosuvastatin calcium.
Description
Each film-coated tablet contains: Rosuvastatin Calcium equivalent to Rosuvastatin 10 mg.
Action
Pharmacology: Pharmacodynamics: 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 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.
Pharmacodynamic effects: Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. It also lowers ApoB, nonHDL-C, VLDL-C, VLDL-TG and increases ApoA-I. Rosuvastatin also lowers the LDL-C/HDL-C, total C/HDL-C and nonHDL-C/HDL-C and the ApoB/ApoA-I ratios.
Pharmacokinetics: Absorption: Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours after oral administration. The absolute bioavailability is approximately 20%.
Distribution: Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.
Metabolism: 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.
Excretion: Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (consisting of absorbed and non-absorbed active substance) and the remaining part is excreted in urine. Approximately 5% is excreted unchanged in urine.
Linearity: Systemic exposure of rosuvastatin increases in proportion to dose. There are no changes in pharmacokinetic parameters following multiple daily doses.
Renal insufficiency: In a study in subjects with varying degrees of renal impairment, mild to moderate renal disease had no influence on plasma concentration of rosuvastatin or the N-desmethyl metabolite. Subjects with severe impairment (CrCl <30 mL/min) had a 3-fold increase in plasma concentration and a 9-fold increase in the N-desmethyl metabolite concentration compared to healthy volunteers.
Hepatic insufficiency: In a study with subjects with varying degrees of hepatic impairment there was no evidence of increased exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below.
Pediatric population: The pharmacokinetic parameters in pediatric patients with heterozygous familial hypercholesterolaemia aged 10 to 17 years have not been fully characterised.
Indications/Uses
Treatment of hypercholesterolaemia: Adults, adolescents and children aged 6 years or older with primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) or mixed dyslipidaemia (type IIb) as adjunct to diet when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.
Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or such treatments are not appropriate.
Prevention on 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.
Dosage/Direction for Use
Before treatment initiation the patient should be placed on a standard cholesterol-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.
Rosuvastatin may be given at any time of day, with or without food.
Treatment of hypercholesterolaemia: The recommended start dose is 5 mg or 10 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor. The choice of start dose should take into account the individual patient's cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. A dose adjustment to the next dose level can be made after 4 weeks, if necessary. In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses, a final titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolaemia at high cardiovascular risk (in particular those with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg, and in whom routine follow-up will be performed. Specialist supervision is recommended when the 40 mg dose is initiated. Or as prescribed by the physician.
Prevention of cardiovascular events: In the cardiovascular events risk reduction study, the dose used was 20 mg daily.
Pediatric population: Pediatric use should only be carried out by specialists.
Children and adolescents 10 to 17 years of age (boys Tanner Stage II and above, and girls who are at least 1 year post-menarche): In children and adolescents with heterozygous familial hypercholesterolaemia the usual start dose is 5 mg daily. The usual dose range is 5-20 mg orally once daily. Titration should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations. Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment. Safety and efficacy of doses greater than 20 mg have not been studied in this population.
Children younger than 10 years: Experience in children younger than 10 years is limited to a small number of children (aged between 8 and 10 years) with homozygous familial hypercholesterolaemia. Therefore, Rosuvastatin is not recommended for use in children younger than 10 years.
Use in the elderly: A start dose of 5 mg is recommended in patients >70 years. No other dose adjustment is necessary in relation to age.
Dosage in patients with renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is 5 mg in patients with moderate renal impairment (creatinine clearance of <60 mL/min). The 40 mg dose is contraindicated in patients with moderate renal impairment. The use of Rosuvastatin in patients with severe renal impairment is contraindicated for all doses.
Dosage in patients with hepatic impairment: There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9. In these patients an assessment of renal function should be considered. There is no experience in subjects with Child-Pugh scores above 9. Rosuvastatin is contraindicated in patients with active liver disease.
Race: Increased systemic exposure has been seen in Asian subjects. The recommended start dose is 5 mg for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients.
Dosage in patients with pre-disposing factors to myopathy: The recommended start dose is 5 mg in patients with predisposing factors to myopathy.
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. Liver function and CK levels should be monitored. Haemodialysis is unlikely to be of benefit.
Contraindications
Rosuvastatin is contraindicated: in patients with hypersensitivity to rosuvastatin or to any of the excipients; in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN); in patients with severe renal impairment (creatinine clearance <30 mL/min); in patients with myopathy; in patients receiving concomitant ciclosporin; during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include: moderate renal impairment (creatinine clearance < 60 mL/min); hypothyroidism; personal or family history of hereditary muscular disorders; previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate; alcohol abuse; situations where an increase in plasma levels may occur; Asian patients; concomitant use of fibrates.
Special Precautions
Renal Effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Rosuvastatin, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease. The reporting rate for serious renal events in post-marketing use is higher at the 40 mg dose. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
Skeletal Muscle Effects: Effects on skeletal muscle e.g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in Rosuvastatin-treated patients with all doses and in particular with doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors.
As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Rosuvastatin in post-marketing use is higher at the 40 mg dose.
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.
Before Treatment: Rosuvastatin, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis.
Whilst on Treatment: Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5xULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5x ULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing Rosuvastatin or an alternative HMG-CoA reductase inhibitor at the lowest dose with close monitoring. Routine monitoring of CK levels in asymptomatic patients is not warranted.
Rosuvastatin should not be used 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, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
Liver Effects: As with other HMG-CoA reductase inhibitors, Rosuvastatin should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.
Protease inhibitors: The concomitant use with protease inhibitors is not recommended.
Lactose intolerance: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Interstitial lung disease: Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. Presenting features can include dyspnea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.
Diabetes Mellitus: Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate.
Use in Children: The evaluation of linear growth (height), weight, BMI (body mass index), and secondary characteristics of sexual maturation by Tanner staging in paediatric patients 10 to 17 years of age taking rosuvastatin is limited to a one-year period.
Use In Pregnancy & Lactation
Rosuvastatin is contraindicated in pregnancy and lactation.
Women of child bearing potential should use appropriate contraceptive measures. Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans.
Adverse Reactions
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.
The frequencies of adverse events are ranked according to the following: Common (>1/100, <1/10); Uncommon (>1/1,000, <1/100); Rare (>1/10,000, <1/1000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
Immune system disorders: Rare: hypersensitivity reactions including angioedema.
Endocrine disorders: Common: diabetes mellitus.
Nervous system disorders: Common: headache, dizziness.
Gastrointestinal disorders: Common: constipation, nausea, abdominal pain.
Rare: pancreatitis.
Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash and urticaria.
Musculoskeletal, connective tissue and bone disorders: Common: myalgia.
Rare: myopathy (including myositis) and rhabdomyolysis.
General disorders: Common: asthenia.
Frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI >30 kg/m2, raised triglycerides, history of hypertension).
As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent.
Renal effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with Rosuvastatin. Shifts in urine protein from none or trace to ++ or more were seen in <1% of patients at some time during treatment with 10 and 20 mg, and in approximately 3% of patients treated with 40 mg. A minor increase in shift from none or trace to + was observed with the 20 mg dose. In most cases, proteinuria decreases or disappears spontaneously on continued therapy. Haematuria has been observed in patients treated with Rosuvastatin and clinical trial data show that the occurrence is low.
Skeletal muscle effects: Effects on skeletal muscle e.g. myalgia, myopathy (including myositis) and, rarely, rhabdomyolysis with and without acute renal failure have been reported in Rosuvastatin-treated patients with all doses and in particular with doses > 20 mg.
A dose-related increase in CK levels has been observed in patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient. If CK levels are elevated (>5xULN), treatment should be discontinued.
Liver effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in transaminases has been observed in a small number of patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient.
Paediatric population: Creatine kinase elevations >10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently in a 52-week clinical trial of children and adolescents compared to adults. In other respects, the safety profile of rosuvastatin was similar in children and adolescents compared to adults.
Drug Interactions
Ciclosporin: During concomitant treatment with Rosuvastatin and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers.
Concomitant administration did not affect plasma concentrations of ciclosporin.
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 International Normalised Ratio (INR).
Ezetimibe: Concomitant use of Rosuvastatin and ezetimibe resulted in no change to AUC or Cmax for either drug.
Gemfibrozil and other lipid-lowering products: Concomitant use of Rosuvastatin and gemfibrozil resulted in a 2-fold increase in rosuvastatin Cmax and AUC.
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure. Concomitant use of rosuvastatin in HIV patients receiving protease inhibitors is not recommended.
Antacid: The simultaneous dosing of Rosuvastatin with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in Rosuvastatin plasma concentration of approximately 50%.
Erythromycin: Concomitant use of Rosuvastatin and erythromycin resulted in a 20% decrease in AUC (0-t) and a 30% decrease in Cmax of Rosuvastatin.
Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of Rosuvastatin and an oral contraceptive resulted in an increase in ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
ATC Classification
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
Presentation/Packing
FC tab 10 mg x 30's.
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