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RAZEL

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CAD in India

(IHD) or CAD) is affecting the Indianpopulation like an epidemic in this new

millennium

CAD is affecting Indians 5-10 years earlierthan other countries

The risk of CAD in Indians is 3-4 times

higher than White Americans, 6-timeshigher than Chinese, and 20-times higher

than Japanese

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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%)

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LDL-C as the Major

Risk Factor NCEP (ATP III guideline) still

recognizes LDL-C as the number one

risk factor in the development ofatherosclerosis

LDL-C is the primary goal in

management of dyslipidemia.

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(2001 National Cholesterol Education

Program Guidelines)

Goal mg/dL

Drug Therapy

No CHD and 0-1 risk factors

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Statins in Dyslipidemia

Excellent tolerability and positive

impact on morbidity and mortality

makes statins first choice for most

patients with dyslipidemia.

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Some important studies

of Statins

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Need of a SUPER STATIN

Higher Potency Reducing triglyceride level also

Increase in HDL

Management of Severe / Familialhyperlipidemia

More hepatoselectivity

Diabetic dyslipidemia Emergence of non-HDL cholesterols and

ApoB as atherogens

Drug-drug interactions

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Properties of an Ideal Statin

Effectively reduce LDL-C (NCEP goal) at therecommended starting dose

Should effectively reduce triglycerides, non

HDL-C and ApoB and increase HDL.

Should be more potent to ensure maximum

inhibition of HMG CoA reductase

Hepato-selective.

Optimal pharmacokinetics (relation to food, time

of administration during anytime of the day).

Less potential for drug-drug interactions

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RAZEL (Rosuvastatin)

First statins to be introduced was Lovastatin,followed by Pravastatin, Fluvastatin, Simvastatin

and Atorvastatin.

We have introduced the latest statin

Rosuvastatin, which is also learned as superstatin, for the first time in India.

Cerivastatin was withdrawn due to high

incidence of rhabdomyolysis We also have introduced the most powerful

statin, called the SUPER STATIN

Rosuvastatin

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Description

Rosuvastatin (RAZEL) is a totally synthetic,

orally active molecule containing a novelseries of methane-sulfonamide group,

which makes it more hydrophilicthan other

statins.

US FDA has approved Rosuvastatin

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Mode of action

Acetyl CoA + Acetyl CoA

Acetoacetyl CoA

HMG CoA (3 - H ydroxy3 - methylglutaryl CoA )

Mevalonic acid

Cholesterol

RAZELHMG CoAreductase

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Mode of Action Causes upregulation of LDL cholesterol

receptors in the liver, thereby increasingclearance of LDL cholesterol from the plasma.

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.

RAZEL exerted anti-inflammatory

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Pharmacological actions

Potency (highest) Hepato-selectivity (High)

Action on LDL-C (upto 65%)

LDL Reduction Simvastatin Atorvastatin Rosuvastatin

< 25% 5 10 5

25-35% 10-20 10 5

35-45% 20-40 10-20 5-1045-55% 80 20-40 10-20

55-60% 80 20-40

60-65% 80

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Pharmacological Actions

Action on triglycerides (upto 40%)

Action on HDL (upto 13%); in fact HDL

decreases with increase in Atorvastatindose.

Action on ApoB and non HDL-C

Action on Metabolic Syndrome

Pleotropic effectreduce MMP

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Pharmacokinetics

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Indications

US FDA has approved Rosuvastatin for

the treatment of dyslipidemia.

RAZEL is recommended as an adjunct todiet and exercise for the treatment of

various lipid disorders including

Hypercholesterolemia Mixed dyslipidemia and

Isolated hypertriglyceridemia

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Dosage

Usual starting dose is 5-10 mg once daily

Adjustment to 20 mg can be made after 4

weeks, if necessary.

Rosuvastatin 40 mg should only be used in

patients with severe hypercholesterolemias

who do not achieve their treatment goal on 20mg.

Rosuvastatin may be given at any time of day,

with or without food.

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Adverse effects

RAZEL is very well tolerated compared to

other statins.

The most common adverse effectsreported are pharyngitis, pain, headache,

flue syndrome, myalgia.

Rhabdomyolysis has been reported withonly 80 mg dose (0.2%)

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Contraindications

Hypersensitivity to Rosuvastatin

Pregnant and Nursing mothers

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Precautions

Patients with history of

hypersensitivity to other statins.

Patients with liver disease

Patients with myopathy.

Patients receiving concomitant

cyclosporine.

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Precaution

Carcinogenesis, mutagenesis, impairment

of fertility

Not reported

Pregnancy

Safety has not been established

Nursing Mothers

Safety has not been established

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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.

Renal insufficiency:

Pharmacokinetics is not affected by mild to moderate renal

impairment.

Hepatic insufficiency:

The pharmacokinetics is not affected by mild to moderate

hepatic impairment.

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Drug Interactions

Cytochrome P450 2C9 and 2C19 are

the primary metabolic enzymes

No significant drug interactions has

been observed

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Features & Benefits

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Features & Benefits

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Rosuvastatin: Salient Features Selective and competitive inhibitor of HMG-CoA

reductase

Most potent HMG-CoA inhibitor (statin)

Hepatoselective statin- Less lipophilic than atorvastatin,

simvastatin, lovastatin and fluvastatin

Cardioprotective, vasoprotective and anti-inflammatory

actions independent of its lipid lowering properties

Limited systemic availability

No metabolism by CYP 450-3A4 enzyme- low

propensity for drug interactions

Plasma elimination half- life is 20 hours- longer duration

of action

No dosage adjustment required in elderly individuals

and patients with mild to moderate hepatic/ renal

insufficiency

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Rosuvastatin: Salient Features

Excellent overall clinical efficacy Excellent efficacy in reducing LDL-C (Upto 65%

reduction- 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- Lowest rate of withdrawalthan other statins

Convenient dosage schedule- Once a day

administration during any time of the day.

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Comparison of RAZEL with Atorvastatin

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Comparison of RAZEL with Atorvastatin

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TH NK YOU