OMNITOR (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 of cholesterol. In vivo studies in animals and in vitro studies in cultured animal and human cells have shown rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering.
OMNITOR (Rosuvastatin) reduces total cholesterol (total-C), LDL-C, ApoB, and non HDL-C (total cholesterol minus HDL-C) in patients with homozygous and heterozygous familial hypercholesterolemia (FH), nonfamilial forms of hypercholesterolemia, and mixed dyslipidemia. Rosuvastatin also reduces TG and produces increases in HDL-C. Rosuvastatin reduces total-C, LDL-C, VLDL-cholesterol (VLDL-C), ApoB. nonHDL-C and TG, and increases HDL-C in patients with isolated hypertriglyceridemia. The effect of rosuvastatin on cardiovascular morbidity and mortality has not been determined.

Absorption: The absolute bioavailability of rosuvastatin is approximately 20%.
Administration of OMNITOR (Rosuvastatin) with food decreased the rate of drug absorption by 20% as assessed by Cmax, but there was no effect on the extent of absorption as assessed by AUC.
Plasma concentrations of rosuvastatin do not differ following evening or morning drug administration.
Significant LDL-C reductions are seen when OMNITOR (Rosuvastatin) is given with or without food, and regardless of the time of day of drug administration.

Distribution: Mean volume of distribution at steady-state of OMNITOR (Rosuvastatin) is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.

Metabolism: OMNITOR (Rosuvastatin) is not extensively metabolized: approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin which is formed principally by cytochrome P450 2C9.

Excretion: Following oral administration, OMNITOR (Rosuvastatin) and its metabolites are primarily excreted in the feces (90%). Te elimination half-life (t1/2) of rosuvastatin is approximately 19 hours.

Indications and usage:
Rosuvastatin is indicated:
- As an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, non HDL-C and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Type IIa and IIb)

-As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV)

- To reduce LDL-C, total-C and ApoB in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Dosage and adminstration: The patient should be placed on a standard cholesterol-lowering diet before receiving rosuvastatin and should continue on this diet during treatment. OMNITOR (Rosuvastatin) can be administered as a single dose at any time of day, with or without food.
Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Type IIa and IIb)
The dose range for OMNITOR (Rosuvastatin) is 5 to 40mg once daily. Therapy with rosuvastatin should be individualized according to goal of therapy and response. The usual recommended starting dose of rosuvastatin is 10mg once daily.
Homozygous Familial Hypercholesterolemia: The recommended starting dose of OMNITOR (Rosuvastatin) is 20mg once daily in patients with homozygous FH. The maximum recommended daily dose is 40mg.
Dosage in patients taking Cyclosporine: In patients taking cyclosporine, therapy should be limited to OMNITOR (Rosuvastatin) 5mg once daily.

Concomitant Lipid-Lowering Therapy: The effect of OMNITOR (Rosuvastatin) on LDL-C and total-C may be enhanced when used in combination with a bile acid binding resin.

Contraindications: OMNITOR (Rosuvastatin) is contraindicated in patients with a known hypersensitivity to any component of this product.
Rosuvastatin is contraindicated in patients with active liver disease or with unexplained persistent elevations of serum transaminases.

Adverse reactions: OMNITOR (Rosuvastatin) is generally well tolerated. Adverse reactions have usually been mild and transient. The most frequent adverse events thought to be related to rosuvastatin were myalgia, constipation, asthenia, abdominal pain and nausea.

Warnings and special precautions:
- OMNITOR (Rosuvastatin) should be prescribed with caution in patients with predisposing factors for myopathy, such as renal impairment, advanced age and inadequately treated hypothyroidism.
- Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Rosuvastatin therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected.
- OMNITOR (Rosuvastatin) therapy should also be temporarily withheld 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, dehydration, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures)
Before instituting therapy with OMNITOR (Rosuvastatin), an attempt should be made to control hypercholesterolemia with appropriate diet and exercise, weight reduction in obese patients and treatment of underlying medical problems.

Pregnancy:
Pregnancy Category X
OMNITOR (Rosuvastatin) may cause fetal harm when administered to a pregnant woman. Rosuvastatin is contraindicated in women who are or may become pregnant. Safety in pregnant women has not been established. There are no adequate and well-controlled studies of rosuvastatin in pregnant women.
Nursing Mothers: It is not known whether OMNITOR (Rosuvastatin) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from rosuvastatin, a decision should be made whether to discontinue nursing or administration of rosuvastatin taking into account the importance of the drug to the lactating woman.
Hepatic Impairment: It is recommended that liver function tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter.
Liver enzyme changes generally occur in first 3 months of treatment with rosuvastatin. Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved.
Renal Impairment: Mild to moderate renal impairment (creatinine clearance > 30ml/min/1.73m2) had no influence on plasma concentrations of rosuvastatin when oral doses of 20mg rosuvastatin were administered for 14 days. However, plasma concentrations of rosuvastatin increased to a clinically significant extent (about 3-fold) in patients with severe renal impairment compared with healthy subjects.

Interactions: In vitro and In vivo data indicate that rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent. The following drugs may interact with rosuvastatin
Ketoconazole
Erythromycin
Itraconazole
Fluconazole
Cyclosporine
Warfarin
Digoxin
Fenofibrate
Gemfibrozil
Antacid
Oral contraceptives

Overdosage: 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. Hemodialysis does not significantly enhance clearance of OMNITOR (Rosuvastatin).

Storage: Store at controlled room temperature, 20-25oC (68-77oF).
Protect from light, heat and moisture. Keep all medicines out of the reach of children.