RAZEL

CAD in India
• (IHD) or CAD) is affecting the Indian population like an epidemic in this new millennium • CAD is affecting Indians 5-10 years earlier than other countries • The risk of CAD in Indians is 3-4 times higher than White Americans, 6-times higher than Chinese, and 20-times higher than Japanese

CAD in India
• South Indians have higher prevalence, 7 percent in rural and 14 percent in urban areas.

• Deaths attributed to cardiovascular disease would double in India in the year 1985-2015. (from 11.6% to 33.6%)

LDL-C as the Major Risk Factor • NCEP (ATP III guideline) still recognizes LDL-C as the number one risk factor in the development of atherosclerosis • LDL-C is the primary goal management of dyslipidemia. in .

(2001 National Cholesterol Education Program Guidelines) Goal mg/dL Drug Therapy No CHD and 0-1 risk factors No CHD and 2+ risk factors CHD or CHD equivalent (Diabetes Mellitus) <160 <130 <100 .

Statins in Dyslipidemia Excellent tolerability and positive impact on morbidity and mortality makes statins first choice for most patients with dyslipidemia. .

Some important studies of Statins .

Need of a “SUPER STATIN” • • • • • • Higher Potency Reducing triglyceride level also Increase in HDL Management of Severe / Familial hyperlipidemia More hepatoselectivity Diabetic dyslipidemia • • Emergence of non-HDL cholesterols and ApoB as atherogens Drug-drug interactions .

• Less potential for drug-drug interactions .Properties of an Ideal Statin • Effectively reduce LDL-C (NCEP goal) at the recommended starting dose • Should effectively reduce triglycerides. • Should be more potent to ensure maximum inhibition of HMG CoA reductase • Hepato-selective. non HDL-C and ApoB and increase HDL. time of administration during anytime of the day). • Optimal pharmacokinetics (relation to food.

• We have introduced the latest statin „Rosuvastatin‟.RAZEL (Rosuvastatin) • First statins to be introduced was Lovastatin. for the first time in India. Fluvastatin. called the “SUPER STATIN” – “Rosuvastatin” . which is also learned as „super statin‟. Simvastatin and Atorvastatin. followed by Pravastatin. • Cerivastatin was withdrawn due to high incidence of rhabdomyolysis • We also have introduced the most powerful statin.

which makes it more hydrophilic than other statins. orally active molecule containing a novel series of methane-sulfonamide group. • US FDA has approved Rosuvastatin .Description • Rosuvastatin (RAZEL) is a totally synthetic.

H ydroxy – 3 .Mode of action Acetyl CoA + Acetyl CoA Acetoacetyl CoA HMG CoA (3 .methylglutaryl CoA ) HMG CoA reductase Mevalonic acid RAZEL Cholesterol .

• RAZEL exerted anti-inflammatory . • Affect LDL production by decreasing hepatic production of VLDL and by increasing catabolism of VLDL remnants • Interfere with the hepatic formation of lipoproteins by reducing cholesterol synthesis. • RAZEL increase HDL.Mode of Action • Causes upregulation of LDL cholesterol receptors in the liver. thereby increasing clearance of LDL cholesterol from the plasma.

Pharmacological actions • Potency (highest) • Hepato-selectivity (High) • Action on LDL-C (upto 65%) LDL Reduction Simvastatin Atorvastatin Rosuvastatin < 25% 25-35% 35-45% 45-55% 55-60% 60-65% 5 10-20 20-40 80 10 10 10-20 20-40 80 5 5 5-10 10-20 20-40 80 .

• Action on ApoB and non HDL-C • Action on Metabolic Syndrome • Pleotropic effect – reduce MMP .Pharmacological Actions • Action on triglycerides (upto 40%) • Action on HDL (upto 13%). in fact HDL decreases with increase in Atorvastatin dose.

Pharmacokinetics .

Indications • US FDA has approved Rosuvastatin for the treatment of dyslipidemia. • RAZEL is recommended as an adjunct to diet and exercise for the treatment of various lipid disorders including – – Hypercholesterolemia – Mixed dyslipidemia and – Isolated hypertriglyceridemia .

if necessary. . with or without food.Dosage • Usual starting dose is 5-10 mg once daily • Adjustment to 20 mg can be made after 4 weeks. • Rosuvastatin may be given at any time of day. • Rosuvastatin 40 mg should only be used in patients with severe hypercholesterolemias who do not achieve their treatment goal on 20 mg.

myalgia. • The most common adverse effects reported are pharyngitis.Adverse effects • RAZEL is very well tolerated compared to other statins. headache. pain. flue syndrome.2%) . • Rhabdomyolysis has been reported with only 80 mg dose (0.

Contraindications • Hypersensitivity to Rosuvastatin • Pregnant and Nursing mothers .

Precautions • Patients with history of hypersensitivity to other statins. • Patients receiving concomitant cyclosporine. • Patients with liver disease • Patients with myopathy. .

Precaution Carcinogenesis. impairment of fertility • Not reported Pregnancy • Safety has not been established Nursing Mothers • Safety has not been established . mutagenesis.

• Renal insufficiency: – Pharmacokinetics is not affected by mild to moderate renal impairment. .Precautions Pediatric Use • Pediatric experience is limited to a small number of children (aged 8 years or above) with homozygous familial hypercholesterolemia. Special populations: • Age and sex: – No clinically relevant effect on the pharmacokinetics of Rosuvastatin. • Hepatic insufficiency: – The pharmacokinetics is not affected by mild to moderate hepatic impairment.

Drug Interactions • Cytochrome P450 2C9 and 2C19 are the primary metabolic enzymes • No significant drug interactions has been observed .

Features & Benefits .

Features & Benefits .

vasoprotective and anti-inflammatory actions independent of its lipid lowering properties • Limited systemic availability • No metabolism by CYP 450-3A4 enzyme.Rosuvastatin: Salient Features • Selective and competitive inhibitor of HMG-CoA reductase • Most potent HMG-CoA inhibitor (statin) • Hepatoselective statin. lovastatin and fluvastatin • Cardioprotective.Less lipophilic than atorvastatin.low propensity for drug interactions • Plasma elimination half. simvastatin.longer duration of action • No dosage adjustment required in elderly individuals and patients with mild to moderate hepatic/ renal insufficiency .life is 20 hours.

Rosuvastatin: Salient Features • Excellent overall clinical efficacy • Excellent efficacy in reducing LDL-C (Upto 65% reduction. .Lowest rate of withdrawal than other statins • Convenient dosage schedule.Once a day administration during any time of the day.better than any other statin) • Most effective statin in increasing HDL-C • Substantial reduction in serum triglycerides • Percentage of patients achieving NCEP treatment goals is very high • Well tolerated drug.

Comparison of RAZEL with Atorvastatin .

Comparison of RAZEL with Atorvastatin .

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