COMPOSITION

Each film-coated tablet contains:

ATORNET - 5
Each film-coated tablet contains: 
Atorvastatin calcium equivalent to Atorvastatin ... 5mg
ATORNET - 10 
Each film-coated tablet contains: 
Atorvastatin calcium equivalent to Atorvastatin ... 10 mg
ATORNET-20
Each film-coated tablet contains:
Atorvastatin calcium equivalent to Atorvastatin ... 20mg


DESCRIPTION

Atorvastatin is a selective competitive inhibitor of 3-hydroxy-3-methyl-glutaryl- coenzyme A (HMG-CoA) reductase enzyme. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the synthesis of cholesterol.
In animal models, atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic low density lipoprotein (LDL) receptors on the cell surface to enhance uptake and catabolism of LDL; atorvastatin also reduces LDL production and the number of LDL particles. Atorvastatin reduces LDL-cholesterol (LDL-C) in some patients with homozygous familial hypercholesterolemia, a population that rarely responds to other lipid- lowering medication(s).
The primary site of action of HMG-CoA reductase inhibitors is the liver. Inhibition of cholesterol synthesis in the liver leads to upregulation of LDL-receptors and an increase in LDL- catabolism. There is also some reduction of LDL production as a result of inhibition of hepatic synthesis of very low density lipoprotein (VLDL), the precursor of LDL-C. Atorvastatin reduces total cholesterol, LDL-C and apo B in patients with homozygous and heterozygous familial hypercholesterolemia, non familial forms of hypercholesterolemia and mixed dyslipidemias. Atorvastatin also reduces VLDL-cholesterol (VLDL-C) and triglycerides and produces variable increases in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1. Atorvastatin reduces total cholesterol, LDL-C, VLDL-C, apo B, triglycerides, and non-HDL-C, and increases HDL-C in patients with isolated hypertriglyceridemia. Atorvastatin also reduces intermediate density lipoprotein cholesterol (IDL-C) in patients with dysbetalipoproteinemia. Atorvastatin as well as some of its metabolites are pharmacologically active in humans. Drug dosage rather than systemic drug concentration correlates better.
 
INDICATIONS
 
PREVENTION OF CARDIOVASCULAR DISEASE
In adult patients without clinically evident coronary heart disease (CHD), but with multiple risk factors for CHD such as age, smoking, hypertension, low HDL-C, or a family history of early CHD,

ATORNET is indicated to:

      Reduce the risk of myocardial infarction
      Reduce the risk of stroke
      Reduce the risk for revascularization procedures and angina

In patients with type 2 diabetes, and without clinically evident CHD, but with multiple risk factors for CHD such as retinopathy, albuminuria, smoking, or hypertension,

ATORNET is indicated to:

     Reduce the risk of myocardial infarction
     Reduce the risk of stroke

In patients with clinically evident CHD,

ATORNET is indicated to:

    Reduce the risk of non-fatal myocardial infarction
    Reduce the risk of fatal and non-fatal stroke
    Reduce the risk for revascularization procedures
    Reduce the risk of hospitalization for CHF
    Reduce the risk of angina

HYPERCHOLESTEROLEMIA
 
ATORNET is indicated:
As an adjunct to diet to reduce elevated total cholesterol, LDL-cholesterol, apo B and triglyceride levels and to increase HDL-C in patients with primary hypercholesterolaemia (heterozygous familial and nonfamilial) and mixed dyslipidaemia (Fredrickson Types IIa and lIb).
As adjunctive therapy to diet for the treatment of patients with elevated serum triglyceride levels (Fredrickson Type IV). 
For the treatment of patients with primary dysbetalipoproteinaemia (FredricksonType III) who do not respond adequately to diet. 
To reduce total cholesterol and LDL-C in patients with homozygous familial hypercholesterolaemia as an adjunct to other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.
As an adjunct to diet to reduce total cholesterol, LDL-C and apo B levels in boys and menarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolaemia, if after an adequate trial of diet therapy, the following findings are present: 
a. LDL-C remains > 190 mg/dl or 
b. LDL-C remains > 160 mg/dl and 
there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient.
Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterolonly when the response to diet and other nonpharmacological measures has been inadequate [see National Cholesterol Education Program (NCEP) Guidelines, summarized in the table below].
 

TABLE. NCEP GUIDELINES FOR LIPID MANAGEMENT

Risk category

LDL goal (mg/dl)

LDL level at which to consider drug therapy (mg/dl)

CHD or CHD risk equivalents* 
(10-yr risk>20%)
<100 >= 130 
(100-129: drug optional)
2+ risk factors ** (10-yr risk < 20%) <130 10 - yr risk 10%-20%:>= 130 
10 - yr risk <10%: >= 160
0-1 risk factor ** <160 (160-189; LDL - lowering drug optional)

Coronary heart disease or peripheral vascular disease (including symptomatic carotid artery disease).** Other risk factors for coronary heart disease (CHD) include: age (males >= 45 years, females >= 55 years or premature menopause without estrogen replacement therapy); family history of premature CHD, current cigarette smoking, hypertension, confirmed HDL-C =< 40 mg/dL ( =< 0.91 mmol/L); and diabetes mellitus. Subtract 1 risk factor if HDL-C is >= 60 mg/dL ( >= 1.6 mmol/L). After the LDL-C goal has been achieved, if the triglyceride level is still >= 200 mg/dl, non HDL-C (total cholesterol minus HDL-C) becomes a secondary target of therapy. Non HDL-C goals are set 30 mg/dl higher than LDL-C goals for each risk category.

DOSAGE AND ADMINISTRATION
Hypercholesterolaemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidaemia
 
(Fredrickson Types IIa and Iib)
The recommended starting dose of atorvastatin is 10 or 20 mg once daily. Patients who require a large reduction in LDL (more than 45%) may be started at 40 mg once daily. The dosage range is 5 to 80 mg once daily. Atorvastatin can be administered as a single dose at any time of the day, with or without food. Therapy should be individualized according to the goal of therapy and response. After initiation and/or up-titration of atorvastatin, lipid levels should be analysed within 2 to 4 weeks and the dosage adjusted accordingly.
Heterozygous Familial Hypercholesterolaemia in Pediatric Patients (10-17 years of age)
The recommended starting dose of atorvastatin is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
 
Homozygous Familial Hypercholesterolaemia
The dosage of atorvastatin in these patients is 10 to 80 mg daily. Atorvastatin should be used as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) in these patients or if such treatments are unavailable.
Dosage in Patients Taking Cyclosporine, Clarithromycin or a combination of Ritonavir plus
 
Saquinavir or Lopinavir plus Ritonavir
In patients taking cyclosporine, therapy should be limited to ATORNET - 10 once daily. In patients taking clarithromycin or in patients with HIV taking a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, for doses of atorvastatin exceeding 20 mg appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin is employed
 
CONTRAINDICATIONS
Hypersensitivity to any component of this medication Active liver disease or unexplained persistent elevations of serum transaminases exceeding three times the upper limit of normal Pregnancy and Lactation