ROSLIX

(Rosuvastatin Tablets 5mg)

COMPOSITION :

ROSLIX Each Film-coated tablet contains Rosuvastatin calcium equivalent to Rosuvastatin: 5mg

PHARMACOLOGY

Pharmacodynamics

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the ratelimiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol.

Pharmacokinetics

Absorption

In clinical pharmacology studies in man, peak plasma concentrations of Rosuvastatin were reached 3 to 5 hours following oral dosing. Both peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in approximate proportion to Rosuvastatin dose. The absolute bioavailability of Rosuvastatin is approximately 20%. Administration of Rosuvastatin with food did not affect the AUC of Rosuvastatin. The AUC of Rosuvastatin does not differ following evening or morning drug administration.

Excretion

Following oral administration, Rosuvastatin and its metabolites are primarily excreted in the feces (90%). The elimination half-life (t1/2) of Rosuvastatin is approximately 19 hours. After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.

Special Populations

Geriatric :

There were no differences in plasma concentrations of Rosuvastatin between the nonelderly and elderly populations (age > 65 years).

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 20 mg 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 (CLcr < 30 mL/min/1.73m2 ) compared with healthy subjects (CLcr> 80 mL/min/1.73m2).

Hemodialysis :

Steady-state plasma concentrations of Rosuvastatin in patients on chronic hemodialysis were approximately 50% greater compared with healthy volunteer subjects with normal renal function.

Hepatic Impairment :

In patients with chronic alcohol liver disease, plasma concentrations of Rosuvastatin were modestly increased.

INDICATIONS

Hyperlipidemia and Mixed Dyslipidemia. Primary Prevention of Cardiovascular Disease, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, to: Reduce the risk of stroke, Reduce the risk of myocardial infarction, Reduce the risk of arterial revascularization procedures.

DOSAGE AND ADMINISTRATION

The dose range for Rosuvastatin is 5 to 40 mg orally once daily. ROSLIX can be administered as a single dose at any time of day, with or without food.

WARNINGS AND PRECAUTIONS

Drug Interactions

Cyclosporine :

Cyclosporine significantly increased Rosuvastatin exposure. Therefore, in patients taking cyclosporine, therapy should be limited to ROSLIX 5 mg once daily.

Gemfibrozil :

Gemfibrozil significantly increased Rosuvastatin exposure. Therefore, combination therapy with ROSLIX and gemfibrozil should be avoided. If used, do not exceed ROSLIX 10 mg once daily.

Lopinavir/Ritonavir :

The combination of lopinavir and ritonavir significantly increased Rosuvastatin exposure. Therefore, in patients taking a combination of lopinavir and ritonavir, the dose of ROSLIX should be limited to 10 mg once daily. The effect of other protease inhibitors on Rosuvastatin pharmacokinetics have not been examined.

Coumarin Anticoagulants :

Rosuvastatin significantly increased INR in patientsreceiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with ROSLIX

Niacin :

The risk of skeletal muscle effects may be enhanced when Rosuvastatin is used in combination with niacin; a reduction in ROSLIX dosage should be considered in this setting.

Fenofibrate :

When Rosuvastatin was co-administered with fenofibrate no clinically significant increase in the AUC of Rosuvastatin or fenofibrate was observed. The benefit of further alterations in lipid levels by the combined use of ROSLIX with fibrates should be carefully weighed against the potential risks of this combination.

Skeletal Muscle Effects :

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. These risks can occur at any dose level, but are increased at the highest dose (40 mg).

Pregnancy

Rosuvastatin is contraindicated in women who are or may become pregnant.

Nursing mothers

It is not known whether Rosuvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk.

ROSLIX treatment should be advised not to nurse their infants.

UNDESIRABLE EFFECTS

Rosuvastatin is generally well tolerated. The most frequent adverse events thought to be related to Rosuvastatin were headache, myalgia, constipation, asthenia, abdominal pain, and nausea.