Composition:
Each coated tablet Contains: Atorvastatin U.S.P. (as calcium trihydrate) …..10, 20 & 40mg respectively.

Description
ORVA (Atorvastatin calcium) is a synthetic lipid – lowering agent. Atorvastatin is a selective and competitive inhibitor of 3–hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. The enzyme catalyzes the conversion of HMG – CoA to mevalonate, an early and rate – limiting step in cholesterol biosynthesis. Atorvastatin calcium is a white to off-white crystalline powder, which is insoluble in water.

Pharmacology
Orva (Atorvastatin) is rapidly absorbed after oral administration; maximum plasma concentration reaches within 1 to 2 hours. Extent of absorption increases in proportion to dose of Atorvastatin. The absolute bioavailability of Atorvastatin is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is 30%. The low systemic availability is attributed to presystemic clearance in gastrointestinal mucosa and hepatic first pass metabolism. Food decreases the rate and extent of drug absorption by approximately 25% & 9%, respectively. Mean volume of distribution of Orva (Atorvastatin) is 381 liters. Atorvastatin is ≥ 98% plasma protein bound. Atorvastatin is extensively metabolized to ortho and para hydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho and para hydroxylated metabolites is equivalent to that of Atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. Atorvastatin and its metabolites are eliminated primarily in bile following hepatic and extra-hepatic metabolism; however, the drug does not appear to undergo enterohepatic recirculation. The mean plasma elimination half-life of Atorvastatin is 14 hours in humans’ subjects; but that of inhibitory activity for HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites. Less than 2% of a dose of Atorvastatin is recovered in urine following oral administration.

INDICATIONS

Prevention of Cardiovascular Disease
In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such an age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, Orva 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 coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, Orva is indicated to:
  • Reduce the risk of myocardial infarction
  • Reduce the risk of stroke In patients with clinically evident coronary heart disease, Orva 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

Orva is indicated:

• As an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb).
• As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV).
• For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who do not respond adequately to diet.
• To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.
• As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present:
  • LDL-C remains ­ 190 mg/dL or
  • 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.

Therapy with lipid-altering agents should be a component of multiple-risk-factor intervention in individuals at increased risk for atherosclerotic vascular disease due to hypercholesterolemia.

Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.

CONTRAINDICATIONS
Orva (Atorvastatin) is contraindicated in patients, who are hypersensitive to any content of the formulation, who have active liver disease or unexplained persistent elevated serum transaminases level exceeding three times the upper limit of normal, pregnant and breast feeding mothers or in women with child bearing potential, who are not using adequate contraceptive measures.

POSSIBLE ADVERSE EFFECTS
Orva (Atorvastatin) is generally well tolerated. Adverse effects have been usually mild and transient. Most frequently adverse effects reported with Atorvastatin includes constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, asthenia, diarrhea, insomnia, angioneurotic edema, muscles cramps, myositis, myopathy, paraesthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, pruritus, rash, impotence, hyperglycemia, and hypoglycemia. Other adverse reactions includes allergic reactions (like anaphylaxis and urticaria), arthralgia, bullous rashes, (including erythema multiforme, Stevens – Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis and thrombocytopenia.

In clinical studies, Atorvastatin was used concomitantly with antihypertensive agents and estrogen replacements therapy without evidence of clinically significant adverse interactions.

DRUG INTERACTION:
The risk of myopathy is increased when Orva (Atorvastatin) is concurrently administrated with cyclosporine, fibric acid derivatives, erythromycin, azole antifungals and niacin.

WARNINGS
Atorvastatin should be used with caution in patients who consume substantial amount of alcohol and have a history of liver disease or unexplained persistent elevated transaminase levels. Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled seizures). Atorvastatin should not be used during pregnancy and lactation. Safety and efficacy of the drug is not established in pediatric patients; therefore, it should not be used in such cases.

Dosage and Administration
Before starting treatment with Atorvastatin, the patient should be put on standard cholesterol-lowering diet and should continue this diet during treatment with Orva (Atorvastatin). The recommended usual starting dose of Orva (Atorvastatin) is 10mg once daily. The dosage range is 10 to 80 mg once daily. Orva (Atorvastatin) can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance dose of Orva (Atorvastatin) should be individualized according to the patients’ characteristics, such as a goal of therapy and patients’ response. After initiation and upon titration of Orva (Atorvastatin), lipid levels should be analyzed within 2 to 4 weeks and dosage should be adjusted accordingly.

Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia:
The majority of the patients are controlled with 10 mg of Orva (Atorvastatin) once daily. A therapeutic response is evident within 2 weeks and maximum response is usually achieved within 4 weeks. The response is maintained during chronic therapy.

Homozygous Familial Hypercholesterolemia:
The dose of Orva (Atorvastatin) in homozygous familial hypercholesterolemia is 10 to 80 mg once daily. The drug should be used under strict medical supervision/advice.

Special Instruction to the Physician
Renal disease has no influence on the plasma concentrations or lipid lowering effects of Orva (Atorvastatin). Thus, dose adjustment in patients with renal dysfunction is not necessary.

Presentation
Orva (Atorvastatin) 10, 20 & 40 mg tablets are available in Cold -Form Cold-Seal pack of 10’s tablets respectively. Further medical information is available only for doctors on request.

Storage / Precautions
Protect from light & moisture, store below 30oC.
Keep out of the reach of children.

WARNING:
To be sold on the prescription of registered medical practitioner only.