ROSUCOL Rosuvastatin Calcium 10mg Film-Coated Tablet 1's

Liver Enzymes: HMG CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. 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., semi-annually) thereafter. Liver enzyme changes generally occur in the first 3 months of treatment with Rosuvastatin. Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved. Should an increase in ALT or AST of >3 times ULN (upper limit of normal) persist, reduction of dose or withdrawal of Rosuvastatin is recommended. Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Hepatic Insufficiency: Patients with active liver disease or unexplained persistent transaminase elevations are contraindications to the use of Rosuvastatin.
Myopathy/Rhabdomyolysis: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with Rosuvastatin and with other drugs in this class. Uncomplicated myalgia has been reported in Rosuvastatin treated patients. Factors that may predispose patients to myopathy with HMG-CoA reductase inhibitors include advanced age (=65 years), hypothyroidism, and renal insufficiency. The incidence of myopathy increased at doses of Rosuvastatin above the recommended dosage range. Consequently: Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy, such as renal impairment, advanced age, and 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. The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of other lipid-lowering therapies or cyclosporine, the benefit of further alterations in lipid levels by the combined use of Rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of this combination. Combination therapy with Rosuvastatin and gemfibrozil should generally be avoided. The risk of myopathy during treatment with Rosuvastatin may be increased in circumstances which increase Rosuvastatin drug levels. 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, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).

 

HMG-CoA reductase inhibitors are contraindicated during pregnancy and in nursing mothers. Rosuvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient becomes pregnant while taking this drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus.

 

Store at temperatures not exceeding 30°C.

 

Pharmacology: Pharmacodynamics: Mechanism of Action: 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. Studies have shown Rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering. Rosuvastatin produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, it inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles. Rosuvastatin reduces total cholesterol (total-C), LDL-C, ApoB, and non-HDL-C (total cholesterol minus HDL-C). Rosuvastatin also reduces TG and produces increases in HDL-C. Rosuvastatin reduces total-C, LDL-C, VLDL-cholesterol (VLDL-C), ApoB, non-HDL-C and TG, and increases HDL-C in patients with isolated hypertriglyceridemia.
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 (C_max) 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 decreased the rate of drug absorption by 20% as assessed by C_max, 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 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 Rosuvastatin is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radio-labeled dose is recovered as metabolite. The major metabolite is N-desmethyl Rosuvastatin, which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-desmethyl Rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of Rosuvastatin. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by Rosuvastatin.
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.
Renal Insufficiency: 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/1.73 m²).
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 insufficiency: In patients with chronic alcohol liver disease, plasma concentrations of Rosuvastatin were modestly increased. In patients with Child-Pugh A disease, C_max and AUC were increased by 60% and 5%, respectively, as compared with patients with normal liver function. In patients with Child-Pugh B disease, C_max and AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.