Rozatin 5

Rosuvastatin Tablets 5 mg

 Each film coated tablet contains:

Rosuvastatin Calcium

Equivalent to Rosuvastatin 5 mg

Excipients q.s.

Colour: Iron Oxide Red & Titanium Dioxide BP

Chemistry: (E) – (3R, 5S) – 7 – {4 – (4 – Fluorophenyl) – 6 – isopropyl – 2 – [methyl (methylsulfonyl)amino]pyrimidine – 5 – yl} – 3,5 – dihydroxyhept – 6 – enoic acid calcium

Category: Rosuvastatin; belongs to the class of HMG- reductase inhibitors. Used in the treatment of hyperlipidemia.


ROZATIN-5 Light Pink colour Film-Coated oval shape Tablet “5” engraved on one side & plain on another side.


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, non HDL-C, VLDL-C, VLDL-TG and increases ApoA-I. Rosuvastatin also lowers the LDLC/HDL-C, total C/HDL-C and non HDL-C/HDL-C and the ApoB/ApoA-I ratios. Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. It also lowers ApoB, non HDL-C, VLDL-C, VLDL-TG and increases ApoA-I. Rosuvastatin also lowers the LDLC/ HDL-C, total C/HDL-C and non HDL-C/HDL-C and the ApoB/ApoA-I ratios.


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. The volume distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin. Rosuvastatin undergoes limited metabolism (approximately 10%). Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces (consisting of absorbed and non absorbed active substance) and the remaining part is excreted in urine. Approximately 5% is excreted unchanged in urine. The plasma elimination

half-life is approximately 19 hours.

Pharmacokinetics of Rosuvastatin were similar to subjects with normal hepatic function (more extensive hepatic impairment may increase systemic exposure to Rosuvastatin), and most had LDL-C reductions similar to subjects with normal hepatic function.


Treatment of hypercholesterolaemia

Adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia (Type II a including heterozygous familial hypercholesterolaemia) or mixed dyslipidaemia (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.

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.

Dosage and Administration:

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 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 on20 mg, and in whom routine follow-up will be performed. Specialist supervision is recommended when the 40 mg dose is initiated.

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 pediatric patients, as recommended by the pediatric 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. The 40 mg tablet is not suitable for use in pediatric patients.

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

Rosuvastatin is contraindicated in patients with active liver disease.


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.


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 < 30ml/min).

In patients with myopathy.

In patients receiving concomitant ciclosporin. During pregnancy and lactation and in women of child bearing 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)


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 warning and Precaution:

Renal Effects

Reported study showed that 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.

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.

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. 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 (>5xULN) 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 (>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. It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases is greater than 3 times the upper limit of normal. The reporting rate for serious hepatic events (consisting mainly of increased hepatic transaminases) in

post-marketing use is higher at the 40 mg dose. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with Rosuvastatin.


Pharmacokinetic studies show an increase in exposure in Asian subjects compared with Caucasians.

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 dyspnoea, 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

In patients with fasting glucose 5.6 to 6.9 mmol/L, treatment with rosuvastatin has been associated with an increased risk of diabetes mellitus.

Pediatric population

The evaluation of linear growth (height), weight, BMI (body mass index), and secondary characteristics of sexual maturation by Tanner staging in pediatric patients 10 to 17 years of age taking Rosuvastatin is limited to a one-year period.


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). Discontinuation or down-titration of Rosuvastatin may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.

Ezetimibe: Concomitant use of Rosuvastatin and ezetimibe resulted in no change to AUC or C for either drug. However, a pharmacodynamic max interaction, in terms of adverse effects, between Rosuvastatin and ezetimibe cannot be ruled out.

Gemfibrozil and other lipid-lowering products: Concomitant use of Rosuvastatin and gemfibrozil resulted in a 2-fold increase in Rosuvastatin C and AUC. Max 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. Reported data showed that concomitant use of Rosuvastatin in HIV patients receiving protease inhibitors is not recommended.

Antacid: The simultaneous dosing of Rosuvastatin with an antacid suspension containing aluminum 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.

Erythromycin: Concomitant use of Rosuvastatin and erythromycin resulted in a 20% decrease in AUC (0-t) and a 30% decrease in C of Rosuvastatin. Max This interaction may be caused by the increase in gut motility caused by


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. These increased plasma levels should be considered when selecting oral

contraceptive doses.

Cytochrome P450 enzymes: Reported in vitro and in vivo studies showed that Rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.

Pregnancy and Lactation:

Rosuvastatin is contraindicated in pregnancy and lactation. Women of child bearing potential should use appropriate contraceptive measures. Animal studies provide limited evidence of reproductive toxicity. Ifa patient becomes pregnant during use of this product, treatment should be discontinued immediately. Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans.

Effect to Drive and use the machine:

Studies to determine the effect of Rosuvastatin on the ability to drive and use machines have not been conducted. However, based on its pharmacodynamic properties, Rosuvastatin is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.

Adverse Reactions:

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


Nervous system disorders: Very rare: Polyneuropathy, memory loss. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea. Gastrointestinal disorders: diarrhoea. Hepatobiliary disorders: Very rare: Jaundice, hepatitis; rare: Increased transaminases.

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome.

Musculoskeletal disorders: Very rare: Arthralgia.

Renal disorders: Very rare: Haematuria.

General disorders and administration site conditions: Oedema.

Over dosage:

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.

Presentation: Blister of 10 Tablets.

Storage: Store in a dry place below 30°C. Protect from light.

Keep out of reach of children.