Simvastatin Tablets (5mg)

Product name: General name: Simvastatin Tablets English name: Simvastatin Tablets Chinese generic name in Pin Yin: Xinfatating Pian Main Composition: Simvastatin Chemical name: 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetra-hydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1,3,7,8-(2S*,4S*),-8a]]. Chemical formula: C25H38O5 Molecular Weight: 418.57Description: White to off-white tablets or film-coated tablets, White to off-white when decoated.Pharmacology & Toxicology The inactive lactone, simvastatin, is hydrolyzed to its active metabolites after oral absorption. The hydrolysate can in vivo competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. This conversion is an early and rate limiting step in the production of cholesterol within the body. The effect of this inhibition, is that simvastatin reduces total plasma cholesterol and low-density lipoprotein (LDL)-cholesterol concentrations by decreasing the synthesis of cholesterol and increasing the synthesis of low-density lipoprotein (LDL)-receptor in liver. It is also noted that a moderate decrease in serum triglycerides(TG) and an increase in high-density lipoprotein (HDL)-cholesterol concentrations. Therefore, simvastatin has protective and therapeutic effect of atherosclerosis and coronary heart desease(CHD). In mice, simvastatin has carcinogenicity after giving 3- to 4-fold of human dosage. However, it is not noted that the incidence of carcinoma increased in human large scale long-term clinical trial. The studies have demonstrated that simvastatin does not have mutagenic potential.Pharmacokinetics Simvastatin is well absorbed after oral administration, concentration in liver is higher than other tissues after absorption. Simvastatin undergoes extensive first-pass extraction in the liver and is hydrolyzed to metabolites. Its main metaboliteβ-hydroxyacid metabolite and other two metabolites show activity. Both simvastatin and its β-hydroxyacid metabolites are highly bound (approximately 95%) to human plasma proteins. Peak plasma concentration was attained within 1.3 to 2.4 hours postdose. Simvastatin has a plasma half-life(t1/2) of 3 hours. Following an oral dose simvastatin in man, 60% of the dose was excreted in feces and 13% in urine. Curative effect emerges within two weeks of treatment and reaches the peak within 4 to 6 weeks. The therapeutic effect can maintain 4 to 6 weeks even after cessation of dosing because of long-term treatment.Indications: Simvastatin is indicated in: 1. Hypercholesterolaemia (1)Reduction of elevated total, LDL-cholesterol, Apo-B, and triglycerides levels in patients with primary hypercholesterolaemia, heterozygous familial hypercholesterolaemia, and mixed hypercholesterolaemia in whom response to diet and other non-pharmaceutical measures have been inadequate. Simvastatin can also increase high-density lipoprotein (HDL)-cholesterol concentrations and then reduce the ratio of LDL/HDL and total-C/HDL.(2) Reduction of elevated total, LDL-cholesterol, and Apo-B levels in patients with homozygous familial hypercholesterolaemia in whom response to diet and other non-pharmaceutical measures have been inadequate. 2. Coronary Heart Disease (1) Reduce the risk of total mortality; (2) Reduce the risk of mortality by decreasing coronary death and the risk of non-fatal myocardial infarction; (3) Reduce the risk of stroke and transient cerebral ischemia; (4) Reduce the risk of undergoing myocardial revascularization procedures (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty); (5) Simvastatin is also indicated to delay the progression of coronary atherosclerosis, including incidence of new focus and fully blocked.Dosage and Directions for Use: For oral administration. Break a tablet off with fingers and thumb for smaller dose when needed. 1 Hypercholesterolaemia The usual initial dose is 10mg/day (5mg tablet: 2 tablets; 10mg tablet: 1 tablet; 20mg tablet: half a tablet) given as a single dose in the evening. The initial dose for the patients with slightly or moderately elevated cholesterol levels is 5 mg/day (5mg tablet: 1 tablet; 10mg tablet: half a tablet; 20mg tablet: 1/4 tablet). The dosage may be adjusted, if needed, but at intervals of more than 4 weeks. The maximum dosage that may be given is 40mg daily (5mg tablet: 8 tablets; 10mg tablet: 4 tablets; 20mg tablet: 2 tablets) as a single dose in the evening. If LDL-cholesterol levels fall below 75mg/dL (1,94 mmol/L) or total plasma cholesterol levels fall below 140mg/dL /L (3,6mmol) consideration should be given to a reduction in dose of SIMVASTATIN.2 Homozygous Familial Hypercholesterolaemia Based on the results from the controlled clinical studies, the recommended dosage for patients with homozygous familial hypercholesterolaemia is 40 mg/day given as a single dose in the evening or 80 mg/day in 3 divided doses of 20 mg, 20 mg, and an evening dose of 40 mg. Simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable, simvastatin can be used alone. 3 Coronary Heart Disease A starting dose of 20mg/day (5mg tablet: 4 tablets; 10mg tablet: 2 tablets; 20mg tablet: 1 tablet) may be given as a single dose in the evening. The dosage may be adjusted, if needed, in accordance with the instructions under Hypercholesterolaemia.4 Concomitant Therapy Simvastatin is effective as a single agent. It is also effective when used in combination with bile-acid sequestrants. If simvastatin is used in combination with immunosuppressive agents, the recommended dose of simvastatin is 10 mg/day (5mg tablet: 2 tablets; 10mg tablet: 1 tablet; 20mg tablet: 1/2 tablet). 5 Renal Insufficiency Patients with moderate renal insufficiency may not require dosage adjustments due to the fact that simvastatin does not undergo significant renal excretion. Implementation of dosages above 10mg/day (5mg tablet: 2 tablets; 10mg tablet: 1 tablet; 20mg tablet: 1/2 tablet) require careful consideration and caution in patients with severe renal insufficiency (creatine clearance <30mL/min).Storage:Close tightly and keep dark, store in a cool place.Package: Aluminum packing: 10 tablets/plate, 1- or 2- plates per box.Shelf-life: Two years