COMPOSITION:
AKROZ 5
Each Film-coated tablet contains
rosuvastatin calcium equivalent to rosuvastatin……5mg
AKROZ 10
Each Film-coated tablet contains
rosuvastatin calcium equivalent to rosuvastatin….10mg
THERAPEUTIC CLASS: Dyslipidemic agent
PHARMACOLOGY:
Pharmacodynamic:
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. In in vivo and in vitro studies, 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, rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles.
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%. The 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.
Distribution
The 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 radiolabeled dose is recovered as a metabolite. The major metabolite is N-desmethylrosuvastatin, which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-desmethylrosuvastatin 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. 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 alcoholic 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, Cmax and AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.
INDICATIONS:
Hyperlipidemia and Mixed Dyslipidemia
Hypertriglyceridemia
DOSAGE AND ADMINISTRATION:
The dose range for rosuvastatin is 5 to 40 mg orally once daily. Rosuvastatin can be administered as a single dose at any time of day, with or without food. When initiating rosuvastatin therapy or switching from another HMG-CoA reductase inhibitor therapy, the appropriate rosuvastatin starting dose should first be utilized, and only then titrated according to the patient’s response and individualized goal of therapy. The 40 mg dose of rosuvastatin should be used only for those patients who have not achieved their LDL-C goal utilizing the 20 mg dose.
CONTRAINDICATIONS:
– Patients with a known hypersensitivity to any component of this product.
– Hypersensitivity reactions including rash, pruritus, Urticaria, and angioedema have been reported with rosuvastatin.
– Patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels
– Women who are pregnant or may become pregnant.
-Nursing mothers
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.
OVERDOSAGE:
There is no specific treatment in the event of an overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Hemodialysis does not significantly enhance the clearance of rosuvastatin.