Product Overview
[Drug Name]
Generic Name: Simvastatin Tablets
Trade Name: Jingbishuxin
English Name: Simvastatin
Chinese Pinyin: Xinfatating Pian
[Ingredients]
The main ingredient of this product is simvastatin. Molecular formula: C₂₅H₃₅O₅ Molecular weight: 418.57
[Appearance]
Film-coated tablets, appear white or off-white after removal of the film coating.
[Indications]
1. Hyperlipidemia. 1) For patients with primary hypercholesterolemia, including heterozygous familial hypercholesterolemia, hyperlipidemia, or mixed hyperlipidemia, when dietary control and other non-drug treatments are unsatisfactory, this product can be used in combination with dietary control to lower elevated total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. It can also increase high-density lipoprotein cholesterol, thereby reducing low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and the total-to-high-density lipoprotein cholesterol ratio. 2) For patients with homozygous familial hypercholesterolemia, this drug can be used in combination with dietary and non-dietary therapies to lower elevated total cholesterol, LDL cholesterol, and apolipoprotein B. 2. Coronary Heart Disease. For patients with coronary heart disease and hypercholesterolemia, this drug is indicated for: 1) Reducing the risk of death. 2) Reducing the risk of coronary heart disease death and non-fatal myocardial infarction. 3) Reducing the risk of stroke and transient ischemic attack. 4) Reducing the risk of cardiac revascularization surgery (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty) and slowing the progression of coronary atherosclerosis, including reducing the formation of new lesions and total blockages. 3. Children with Heterozygous Familial Hypercholesterolemia. For adolescent boys and girls aged 10-17 years (at least 1 year after menarche) with heterozygous familial hypercholesterolemia, this drug can be used in combination with dietary control to lower total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides.
[Dosage and Administration]
Patients should follow a standard cholesterol diet before starting simvastatin therapy and continue this diet during treatment.
Hypercholesterolemia: The initial dose is generally 10 mg daily, taken in the evening. For patients with mild to moderately elevated cholesterol levels, the initial 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.
The simvastatin dose should be reduced when the LDL cholesterol level drops to 75 mg/dL (1.94 mmol/L) or the total cholesterol level drops below 140 mg/dL (3.6 mmol/L).
Coronary Artery Disease: Patients with coronary artery disease can start with a 20 mg daily evening dose. If dose adjustments are necessary, refer to the instructions above (Usage and Dosage for Hypercholesterolemia).
Concomitant Therapy: Simvastatin is effective when used alone or in combination with a bile acid sequestrant. For patients taking concomitant immunosuppressants, the recommended dose of simvastatin is 10 mg daily. Patients with Renal Impairment: Because simvastatin is not significantly excreted by the kidneys, no dose adjustment is required 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]
1. This product is generally well tolerated, with most adverse reactions being mild and transient. In controlled clinical studies, less than 2% of patients discontinued treatment due to adverse reactions. In pre-marketing controlled clinical studies, adverse reactions considered by investigators to be drug-related (classified as possible, probable, or certain) with an incidence of ≥1% included abdominal pain, constipation, and flatulence; and fatigue and headache, with an incidence of 0.5-0.9%. Myopathy has been reported rarely. 2. In the HPS study (see Clinical Trials), a total of 20,536 patients received either 40 mg of simvastatin (n=10,269) or placebo (n=10,267) daily for a mean observation period of 5 years. The safety profile was similar between the two groups. This large trial only recorded serious adverse reactions and withdrawals due to side effects. Discontinuation rates due to adverse reactions were similar between the two groups (4.8% in the simvastatin group and 5.1% in the placebo group). The incidence of myopathy in the simvastatin group was less than 0.1%. Transaminase elevations (≥3 times the upper limit of normal on repeated measurements) occurred in 0.21% (n=21) of the simvastatin group and 0.09% (n=9) of the placebo group, respectively. 3. In the Nordic Simvastatin Survival Study (4S), 4,444 patients received either 20-40 mg of simvastatin daily (n=2,221) or placebo (n=2,223) for a median follow-up of 5.4 years. Safety and tolerability were similar between the two groups. 4. Reported in uncontrolled clinical studies or post-marketing use.
[Contraindications]
1. Hypersensitivity to any component of this product; 2. Active hepatitis or unexplained persistent elevation of serum transaminases; 3. Pregnant or lactating women.
[Precautions]
1. Hepatic Reactions: In clinical trials, a small number of patients taking simvastatin experienced significant, persistent elevations in serum transaminases (more than three times the normal value). However, after discontinuation of the drug, transaminases returned to pre-treatment levels, without jaundice or other related clinical signs or symptoms, and without allergic reactions. Patients with elevated transaminases should undergo more frequent testing and precautions before treatment. If a patient's transaminase levels continue to rise, particularly if they exceed three times the normal value and remain elevated, the drug should be discontinued. 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 transaminase elevations. As with other lipid-lowering drugs, moderate elevations of transaminases (less than three times the normal value) have been reported in patients treated with simvastatin. These changes typically occur shortly after treatment with simvastatin, are generally transient, and are not associated with any symptoms, so discontinuation of the drug is not necessary. 2. Muscle Reactions: Mild, transient elevations of creatine kinase (CK) (derived from skeletal muscle) are common in patients treated with simvastatin, but these elevations are not clinically significant. Myopathy should be considered in patients with diffuse myalgia, weakness, and/or significant elevations of creatine kinase (CK) phosphate (greater than ten times the normal value). 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 therapy should be discontinued immediately. Treatment with methylhydroxyglutaryl coenzyme A (HMG-CoA) reductase inhibitors should be discontinued in patients with acute or severe condition-suggestive myopathy and those at risk for secondary acute renal failure due to rhabdomyolysis. 3. Ophthalmological Examination: Even in the absence of any drug treatment, the incidence of lens opacities increases with age. Long-term clinical data indicate that simvastatin has no adverse effects on the human lens. 4. Pregnancy: No data are available regarding the use of simvastatin during pregnancy. Simvastatin is contraindicated in pregnant women. Because atherosclerosis is a chronic process, discontinuing lipid-lowering medications during pregnancy has little effect on the long-term efficacy of treatment for primary hypercholesterolemia. Furthermore, cholesterol and other products of its biosynthetic pathway are essential for fetal development, including the synthesis of steroids and cell membranes. Because HMG-CoA reductase inhibitors, such as simvastatin, reduce cholesterol synthesis and may also reduce other products of the cholesterol biosynthetic pathway, simvastatin use during pregnancy may be harmful to the fetus. In women of childbearing age, simvastatin should only be used in women whose pregnancy is unlikely. If a woman becomes pregnant while taking simvastatin, she should discontinue simvastatin and be informed of the potential harm to the fetus. 5. Breastfeeding Women: It is not known whether simvastatin and its metabolites are excreted in human milk, as many drugs are excreted in human milk and because of the potential for serious side effects, women taking simvastatin should not breastfeed. 6. Pediatric Use: The safety and efficacy of simvastatin in children have not been established. Simvastatin is not currently recommended for use in children. 7. Elderly Use: In controlled clinical trials of simvastatin in elderly patients (over 65 years of age), its effects on lowering total cholesterol and LDL-C were comparable to those in other populations, without a significant increase in the frequency of side effects or laboratory abnormalities. 8. Homozygous Familial Hypercholesterolemia: Because patients with homozygous familial hypercholesterolemia completely lack low-density lipoprotein (LDL) receptors, simvastatin is less effective in treating this condition. 9. Hypertriglyceridemia: Simvastatin has only a moderate triglyceride-lowering effect and is not suitable for treating conditions characterized by elevated triglycerides (such as types I, IV, and V hyperlipidemia).
[Use in Special Populations]
Precautions for Children:
The safety and efficacy of this medication in children have not been established. Simvastatin is not currently recommended for children.
Precautions for Pregnancy and Lactation:
Pregnant or lactating women.
Precautions for the Elderly:
In controlled clinical trials of simvastatin in elderly patients (over 65 years of age), its efficacy in lowering total cholesterol and low-density lipoprotein (LDL) cholesterol was comparable to that observed in other populations, without a significant increase in the frequency of adverse reactions or laboratory abnormalities. Drug Interactions: 1. The risk of rhabdomyolysis is increased when simvastatin is coadministered with other drugs that significantly inhibit cytochrome P450 3A4 at therapeutic doses (e.g., cyclosporine, mibefradil, itraconazole, ketoconazole, erythromycin, clarithromycin, and nefazodone), or with fibric acid derivatives or niacin. 2. The incidence and severity of myopathy may be increased when simvastatin is coadministered with methylhydroxyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, including gemfibrozil and other fibrates, and lipid-lowering doses of niacin (≥1 g/day). Furthermore, elevated plasma levels of HMG-CoA reductase inhibitor activity may 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 blood levels of methylhydroxyglutaryl coenzyme A (HMG-CoA) reductase inhibitors and, therefore, increase the risk of myopathy. These drugs include cyclosporine, tetralins, the calcium channel blocker mibefradil, itraconazole, ketoconazole, and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, and the antidepressant nefazodone. 3. Coumarin derivatives: Clinical studies have shown that simvastatin can moderately enhance the anticoagulant effect of coumarin anticoagulants. Therefore, in adults, frequent prothrombin time monitoring is recommended during early anticoagulant therapy and concurrent use of simvastatin to ensure that the prothrombin time does not significantly change. Even after a stable prothrombin time has been achieved in patients taking coumarin derivatives, continued prothrombin time monitoring is recommended for a fixed period. The 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.
[Pharmacological Action]
In two clinical studies, simvastatin was found to moderately enhance the anticoagulant effect of bean-based anticoagulants. Regular monitoring of the prothrombin time should be performed in adults before early anticoagulant therapy and before simvastatin use to determine if there is a significant change in the prothrombin time. Continued monitoring of the prothrombin time for a fixed period is recommended after a stable prothrombin time has been achieved in patients taking bean-based anticoagulants. The 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.
[Storage] Store tightly closed below 30°C. Avoid sudden temperature increases above 50°C.
[Strength] 20 mg
[Packaging Size] 20 mg x 28 tablets
[Expiry Date] 24 months
Approval Number: National Medicine Standard H20000009
Manufacturer: Zhejiang Jingxin Pharmaceutical Co., Ltd.
