Rovex 10/Rovex 20

Rovex 10: White coloured, round shaped, biconvex, film-coated tablets, plain on both sides.
Rosuvastatin Calcium Tablets contains Rosuvastatin as active ingredients. The empirical formula of Rosuvastatin Calcium is Calcium bis [3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[methyl (methylsufonyl) amino]-6-(propan-2-yl) pyrimidin-5-yl] -3,5-dihydroxyhept-6-enoate] is C₄₄H₅₄CaF₂N₆O₁₂S₂ and molecular weight is 1001.141 g/mol.
Each Film-Coated tablet contains: Rosuvastatin Calcium Eq. to Rosuvastatin 10 mg, Excipients q.s.
Rovex 20: White coloured, round, biconvex and film coated tablets.
Each film coated tablet contains: Rosuvastatin Calcium Equivalent to Rosuvastatin 20 mg.
Colour: Titanium Dioxide BP.
Rosuvastatin Calcium is an off-white to creamish white crystalline powder. It is soluble in acetonitrile & slightly soluble in acetone. Its molecular formula is (C₂₂H₂₇FN₃O₆S)₂Ca & its molecular weight is 1001.14.

Pharmacological Classification: HMG CoA Reductase Inhibitor. ATC Code: C10AA07.
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 coenzymeA 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.
Pharmacodynamics: Rosuvastatin is a synthetic, enantiomerically pure antilipemic agent. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and triglyceride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.
Pharmacokinetics: Absorption: Absolute bioavailability is about 20%. C_max is reached in 3 to 5 h. Administration with food did not affect the AUC.
Distribution: The mean steady-state Vd is about 134 L. Rosuvastatin is 88% protein bound, mainly to albumin.
Metabolism: Rosuvastatin's major metabolite is formed by CYP2C9. Not extensively metabolized; approximately 10% is recovered as metabolite.
Elimination: Primarily excreted in the feces (90%). The elimination half-life is approximately 19 h.

Primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) 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 hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

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.
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. 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.
Rosuvastatin Tablets may be given at any time of day, with or without food.
Paediatric use: Safety and efficacy have not been established in children. Paediatric experience is limited to a small number of children (aged 8 years or above) with homozygous familial hypercholesterolaemia. Therefore, Rosuvastatin Tablets is not recommended for paediatric use at this time.
Use in the elderly: A start dose of 5 mg is recommended in patients >70 years, 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 Tablets 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 Tablets 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.
The 40 mg dose is contraindicated in some of these patients.

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.

Rosuvastatin Tablets 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 3x 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.

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. A pharmacodynamic interaction cannot be excluded and caution should be exercised with their combined use.
As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Rosuvastatin Tablets 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 (>5x ULN) a confirmatory test should be carried out within 5-7 days. If the repeat test confirms a baseline CK >5x ULN, 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. Such factors include: renal impairment, hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, age >70 years, situations where an increase in plasma levels may occur concomitant use of fibrates.
In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated at baseline (>5x ULN) treatment should not be started.
While 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 (>5x ULN) 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 Tablets 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.

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.
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.
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. Review of data from clinical trials and post-marketing experience to date has not identified a causal association between proteinuria and acute or progressive renal disease. Haematuria has been observed in patients treated with Rosuvastatin Tablets 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 (>5x ULN), 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.

Ciclosporin: During concomitant treatment with Rosuvastatin Tablets 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 Tablets 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). Discontinuation or down-titration of Rosuvastatin Tablets may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.
Ezetimibe: Concomitant use of Rosuvastatin Tablets and ezetimibe resulted in no change to AUC or C_max for either drug. However, a pharmacodynamic interaction, in terms of adverse effects, between Rosuvastatin Tablets and ezetimibe cannot be ruled out.
Gemfibrozil and other lipid-lowering products: Concomitant use of Rosuvastatin Tablets and gemfibrozil resulted in a 2-fold increase in rosuvastatin C_max and AUC.
Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate, other fibrates and lipid lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of a fibrate. These patients should also start with the 5 mg dose.
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure. In a pharmacokinetic study, co-administration of 20 mg rosuvastatin and a combination product of two protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers was associated with an approximately two-fold and five-fold increase in rosuvastatin steady-state AUC_(0-24) and C_max respectively. Therefore, concomitant use of rosuvastatin in HIV patients receiving protease inhibitors is not recommended.
Antacid: The simultaneous dosing of Rosuvastatin Tablets with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%. This effect was mitigated when the antacid was dosed 2 hours after Rosuvastatin. The clinical relevance of this interaction has not been studied.
Erythromycin: Concomitant use of Rosuvastatin Tablets and erythromycin resulted in a 20% decrease in AUC_(0-t) and a 30% decrease in C_max of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.
Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of Rosuvastatin Tablets and an oral contraceptive resulted in an increase in ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data available in subjects taking concomitant Rosuvastatin Tablets and HRT and therefore a similar effect cannot be excluded. However, the combination has been extensively used in women in clinical trials and was well tolerated.
Other medicinal products: Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected.
Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. 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). Concomitant administration of itraconazole (an inhibitor of CYP3A4) and rosuvastatin resulted in a 28% increase in AUC of rosuvastatin. This small increase is not considered clinically significant. Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected.

Store at temperatures not exceeding 30°C.
Rovex 10: Shelf life: 24 months.
Rovex 20: Protect from light.
Shelf-life: 2 years from the date of manufacturing.

Dyslipidaemic Agents

C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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