Product Overview
[Drug Name]
Generic Name: Simvastatin Dispersible Tablets
Trade Name: Simvastatin Dispersible Tablets (10mg x 14 tablets)
[Main Ingredients]
The main ingredient of this product is simvastatin, whose chemical name is {1S-[1a,3a,7a,80(2S*,4S*)8a])-1,2,3,7,8a-hexahydro-3,7-dimethyl-8-{2-(tetrahydro-4-hydroxy-6-oxy-2H-pyran-2-yl)ethyl 1-1-naphthyl-2-dimethylbutyrate. Its structural formula is: Molecular formula: C-H2O, Molecular weight: 418.57.
[Properties]
This product is a white or off-white tablet.
[Indications/Main Functions]
1. When dietary therapy and other non-drug treatments are inadequate for hypercholesterolemia, simvastatin can be used to lower total cholesterol and low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. Simvastatin can also increase high-density lipoprotein cholesterol and thus reduce the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. In patients with combined hypercholesterolemia and hypertriglyceridemia, when hypercholesterolemia is the main abnormality, it can reduce elevated cholesterol levels. 2. Coronary heart disease and secondary prevention of coronary heart disease. For patients with coronary heart disease, simvastatin is suitable for: (1) reducing the risk of death; (2) reducing the risk of coronary heart disease death and non-fatal myocardial infarction; (3) reducing myocardial revascularization surgery (coronary artery bypass grafting and percutaneous coronary angioplasty); (4) delaying the progression of atherosclerosis, including the occurrence of new lesions and complete blockage. [Specification] 10mg*14 tablets [Usage and Dosage] Patients receiving this product should follow a standard cholesterol-lowering diet before treatment and continue to follow a standard cholesterol-lowering diet during treatment. 1. Hypercholesterolemia: The general starting dose is 10 mg daily, taken in the evening. For patients with mild to moderately elevated cholesterol levels, the starting dose is 5 mg daily. Dose adjustments should be made at least four weeks apart, with a maximum dose of 40 mg daily, taken in the evening. 2. When the LDL cholesterol level drops below 75 mg/dL (1.94 mmol/L) or the total cholesterol level drops below 140 mg/dL (3.6 mmol/L), the simvastatin dose should be reduced. For patients with coronary artery disease, a 0 mg daily dose can be used as the starting dose. 3. Concomitant therapy: Simvastatin is effective when used alone or in combination with a bile acid chelator. For patients taking concurrent immunosuppressants, the recommended dose of simvastatin is 10 mg daily. 4. Patients with Renal Impairment: Because simvastatin is not significantly excreted by the kidneys, dose adjustment is not necessary for patients with moderate renal impairment. However, for patients with severe renal impairment (creatinine clearance <30 mL/min), the use of doses exceeding 10 mg per day should be carefully considered and used with caution.
[Adverse Reactions]
Simvastatin is generally well tolerated, with most side effects being mild and transient. In controlled clinical trials, less than 2% of patients discontinued simvastatin due to side effects. In controlled clinical trials, adverse reactions (classified as possibly, suspected, or definitely) attributed to drug-relatedness at an incidence of greater than 1% included abdominal pain, constipation, and flatulence, while those at an incidence of 0.5%-0.9% included fatigue and headache. Reports of myopathy are rare. The following adverse reactions have been reported in uncontrolled clinical trials or postmarketing use: nausea, diarrhea, rash, dyspepsia, pruritus, alopecia, dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting, and anemia. Rhabdomyolysis and hepatitis/jaundice have rarely occurred. A frank hypersensitivity syndrome with one or more of the following features has been reported rarely: angioedema, lupus-like syndrome, polymyalgia rheumatica, vasculitis, thrombocytopenia, eosinophilia, arthritis, arthralgia, urticaria, fever, pyrexia, flushing, dyspnea, and malaise. Laboratory findings have rarely revealed significant and persistent elevations in serum transaminases. Liver function test abnormalities have been mild or transient. Elevations in serum creatine kinase (CK) derived from skeletal muscle have been reported.
[Contraindications]
This product is contraindicated in the following patients: 1. Hypersensitivity to any component of this product. 2. Active hepatitis or unexplained persistent elevations in serum transaminases. 3. Pregnant or lactating women. 4. Concomitant use with the tetralin calcium channel blocker mibefradil.
[Drug Interactions]
1. The risk of rhabdomyolysis is increased when simvastatin is used in combination with other drugs that significantly inhibit cytochrome P450 3A4 at therapeutic doses (e.g., cyclosporine, mibefradil, itraconazole, ketoconazole, erythromycin, clarithromycin, and nefazodone), or with fibrates or niacin. 2. Concomitant use of simvastatin with methylhydroxyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, including gemfibrozil and other fibrates, and lipid-lowering doses of niacin (≥1 g/day), increases the incidence and severity of myopathy. Furthermore, elevated plasma levels of methylhydroxyglutaryl coenzyme A (HMG-CoA) reductase inhibitor activity may also increase the risk of myopathy. Simvastatin and other HMG-CoA reductase inhibitors are metabolized by the cytochrome P450 isoenzyme 3A4. Several drugs that significantly inhibit this metabolic pathway at therapeutic doses can increase HMG-CoA reductase inhibitor blood levels and, therefore, increase the risk of myopathy. These drugs include cyclophosphamide, tetrahydrocannabinol, the calcium channel blocker mibefradil, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, and the antidepressant nefazodone. Coumarin derivatives: Clinical studies have shown that simvastatin can moderately enhance the anticoagulant effect of coumarin anticoagulants. Therefore, in adults beginning early anticoagulant therapy and concurrently taking simvastatin, frequent prothrombin time measurements should be performed to ensure that the prothrombin time does not significantly change. After a stable prothrombin time is achieved in patients taking coumarin-based biologics, continued prothrombin time monitoring is recommended for a fixed period. This same procedure should be followed if the simvastatin dose is changed. In patients not taking anticoagulants, simvastatin therapy has not been reported to affect bleeding or prothrombin time.
[Precautions]
1. Patients should follow a standard cholesterol diet before receiving simvastatin treatment and continue this diet during treatment. 2. Hepatic Reactions: This drug should be used with caution in patients who consume significant amounts of alcohol and/or have a history of liver disease. Simvastatin should be contraindicated in patients with active liver disease or unexplained elevations in aminotransferase levels. In clinical trials, a small number of patients taking simvastatin experienced significant, persistent elevations in serum aminotransferase levels (more than three times the normal value). However, after discontinuation of the drug, aminotransferase levels returned to pre-treatment levels, without jaundice or other concerning clinical signs or symptoms, and without allergic reactions. Patients with elevated aminotransferase levels should be monitored closely before treatment. If a patient's aminotransferase levels continue to rise, particularly if the elevation exceeds three times the normal value and persists, the drug should be discontinued. As with other lipid-lowering drugs, moderate elevations in aminotransferase levels (less than three times the normal value) have also been reported in patients treated with simvastatin. These changes typically occur shortly after simvastatin treatment begins, but are generally transient and asymptomatic, so discontinuation of the drug is not necessary. 3. Muscle Reactions: Mild, transient elevations in creatine kinase (CK) (derived from skeletal muscle) are common in patients treated with simvastatin, but these elevations are not clinically significant. Diffuse myalgia, weakness, and/or significant elevations in creatine kinase (CK) (greater than ten times the normal value) should be considered a myopathy. Therefore, patients should be advised to report any unexplained myalgia, weakness, or weakness to their doctor immediately. If a significant elevation in creatine kinase (CK) is detected or myalgia is diagnosed or suspected, simvastatin treatment should be discontinued immediately. Treatment with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors should be discontinued in patients with acute or severe conditions suggestive of myopathy or those at risk for secondary acute renal failure due to rhabdomyolysis. 4. Ophthalmological examination: Even without any medication, the incidence of lens opacities increases with age. Long-term clinical studies have shown that simvastatin has no adverse effects on the human lens. 5. Homozygous familial hypercholesterolemia: Because patients with homozygous familial hypercholesterolemia completely lack low-density lipoprotein (LDL) receptors, simvastatin is less effective in treating this condition. 6. Hypertriglyceridemia: Simvastatin has only a moderate effect on lowering triglycerides and is not suitable for treating conditions characterized by elevated triglycerides (such as Types 1. IV and V hyperlipidemia). 7. This drug should be used with caution in patients with excessive alcohol consumption and/or a history of liver disease.
[Pediatric Use]
The safety and efficacy of this medication for pediatric use have not been established and is not recommended for pediatric use.
[Use in Elderly Patients]
See package insert for details.
[Overdose]
Not yet established.
[Pharmacology and Toxicology]
This drug is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-COA) reductase, inhibiting endogenous cholesterol synthesis and acting as a lipid-lowering agent. Simvastatin can lower both normal and elevated low-density lipoprotein cholesterol (LDL-C) levels. Low-density lipoprotein (LDL) is produced from very low-density lipoprotein (VLDL) and is metabolized primarily through binding to LDL receptors. Simvastatin's mechanism of LDL-lowering is through reduced VLDL cholesterol concentration and LDL receptor induction, resulting in reduced LDL-C production and/or increased catabolism. Apolipoprotein B (ApoB) also decreases during simvastatin treatment. Because each LDL particle contains one molecule of ApOB, and because only very low ApOB levels are found in patients with elevated LDL-C (without concomitant elevation of VLDL), this suggests that simvastatin not only lowers cholesterol by lowering LDL but also reduces peripheral LDL particle concentrations. Furthermore, simvastatin lowers VLDL and triglycerides (TG) while increasing HDL-C. The effects of simvastatin on lipoproteins, fibrinogen, and other biochemical markers of coronary artery disease are still unclear.
