Product Overview
[Drug Name]
Generic Name: Simvastatin Tablets
Trade Name: Zocor Simvastatin Tablets 20mg x 7 tablets
[Main Ingredient]
The main ingredient of this product is simvastatin. Scientific Name: 2-Dimethylbutyric Acid-8-{(4R,6R-6-2-(1S,2S,6S,88-1.267.88-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl]ethyltetrakis(4-hydroxy-2H-pyran-2-one)}
[Properties]
This product is a film-coated tablet that appears white or off-white after removal of the coating.
[Indications/Main Functions]
1. Hyperlipidemia. 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 reduce blood cholesterol. Elevated total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides, and elevated high-density lipoprotein cholesterol, thereby reducing the ratio of LDL cholesterol to HDL cholesterol and total cholesterol to HDL cholesterol. 2) For patients with homozygous familial hypercholesterolemia, this product can be used in combination with dietary control 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 product is indicated for: 1) Reducing the risk of death. 2) Reducing the risk of death from coronary heart disease 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. This product is indicated for lowering total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in adolescent boys and girls aged 10-17 years (at least 1 year after menarche) with heterozygous familial hypercholesterolemia, in combination with dietary modification.
[Specifications]
20mg*7 tablets
[Dosage and Administration]
Patients should follow a standard cholesterol-lowering diet before treatment with this product and continue to do so during treatment. The recommended starting dose is 20 mg once daily, taken in the evening. For patients requiring only moderate lowering of LDL cholesterol, the starting dose is 10 mg. The recommended dose for patients taking concomitant cyclosporine, danazol, fibrates (except fenofibrate) or niacin, amiodarone, verapamil, and those with severe renal insufficiency is as follows. The recommended dose range is 5-80 mg once daily, taken in the evening. The dose should be individually adjusted based on baseline LDL cholesterol levels, recommended treatment goals, and patient response, with dose adjustments spaced at least 4 weeks apart. Cholesterol levels should be monitored regularly. If the LDL cholesterol level drops below 75 mg/dL (1.94 mmol/L) or the total plasma cholesterol level drops below 140 mg/dL (3.6 mmol/L), a dose reduction of this drug should be considered. --Homozygous Familial Hypercholesterolemia: Based on the results of a controlled clinical study, the recommended dose of this drug for patients with homozygous familial hypercholesterolemia is 40 mg daily, taken once in the evening; or 80 mg daily, divided into 20 mg, 20 mg, and 40 mg in the evening. This drug can be used in combination with other lipid-lowering therapies (such as LDL aspiration), or it can be used alone when these methods are unavailable.
[Adverse Reactions]
1. This drug 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 controlled pre-marketing 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 was reported rarely. 2. In the HPS study (see Clinical Trials), 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. Withdrawals 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 was less than 0.1% in the simvastatin group. 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), 4444 patients received either 20-40 mg of simvastatin daily (n=2221) or placebo (n=223) for a median follow-up of 5.4 years. Safety and tolerability were similar between the two groups. 4. This has been reported in uncontrolled clinical studies or post-marketing use.
[Contraindications]
1. Hypersensitivity to any component of this product. 2. Active liver disease or persistently elevated serum transaminases. 3. Pregnant and lactating women (see Precautions, Use in Pregnant and Lactating Women).
[Drug Interactions]
1. Interaction with CYP3A4. Simvastatin is metabolized by CYP3A4 but does not inhibit CYP3A4; therefore, it does not affect the plasma concentrations of other drugs metabolized by CYP3A4. Potent CYP3A4 inhibitors (see below) may increase the risk of myopathy by reducing the elimination of simvastatin (see Precautions, Myopathy/Rhabdomyolysis). Itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone. 2. Interactions with other lipid-lowering drugs that can cause myopathy when used alone. The risk of myopathy is increased with the following lipid-lowering drugs. Although these drugs are not effective CYP3A4 inhibitors, they can cause myopathy when used alone: gemfibrozil, other fibrates (except fenofibrate), niacin (>1 gram per day). When fenofibrate is used with simvastatin, there is no evidence that the risk of myopathy exceeds the combined risk of either drug when used alone. 3. Other Interactions. 1) Cyclosporine or Danazol: Concomitant use of cyclosporine or danazol increases the risk of myopathy/rhabdomyolysis, particularly when used with high-dose simvastatin (see Precautions, Myopathy/Rhabdomyolysis). 2) Amiodarone or verapamil: Concomitant use of amiodarone or verapamil with high-dose simvastatin increases the risk of myopathy/rhabdomyolysis (see Precautions, Myopathy/Rhabdomyolysis) 3) Diltiazem: Take diltiazem and simvastatin 80 mg at the same time.
[Precautions]
1. Liver 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 concerning clinical signs or symptoms, and without allergic reactions. Patients with elevated transaminases should be monitored closely before treatment. If transaminases continue to rise, particularly if they exceed three times the normal value and persist, 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 transaminases elevations. As with other lipid-lowering drugs, moderate elevations in transaminases (less than three times the normal value) have also been reported in patients treated with simvastatin. These changes typically occur shortly after treatment with simvastatin but are generally transient and not associated with any symptoms, so discontinuation of the drug is not necessary. 2. Muscle Reactions: Patients treated with simvastatin commonly experience mild, transient elevations in creatine kinase (CK) (derived from skeletal muscle), but these 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. Simvastatin treatment should be discontinued immediately if a significant elevation in CK is detected or myalgia is diagnosed or suspected. Treatment with methylhydroxyglutaryl 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. 3. Ophthalmological Examination: The incidence of lens opacities increases with age, even in the absence of any medication. Long-term clinical data show that simvastatin has no adverse effects on the human lens. 4. Pregnancy Use: No data are available regarding the use of simvastatin in pregnant women. Simvastatin is contraindicated during pregnancy. Because atherosclerosis is a chronic process, discontinuing lipid-lowering medications during pregnancy has little impact on the long-term effectiveness of treating 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 other products of the cholesterol biosynthetic pathway, simvastatin use during pregnancy may be harmful to the fetus. Among women of childbearing age, simvastatin should only be used in those with a low probability of pregnancy. If a woman becomes pregnant while taking simvastatin, simvastatin should be discontinued and the woman should 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. Because many drugs are excreted in human milk, and given the potential serious side effects of this drug, breastfeeding women taking simvastatin should not be administered. 6. Pediatric Use: The safety and effectiveness of this drug in children have not been established. Simvastatin is not currently recommended for children. 7. Elderly Use: 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 side effects or laboratory abnormalities. 8. Homozygous Familial Hypercholesterolemia: Because patients with homozygous familial hypercholesterolemia completely lack the low-density lipoprotein (LDL) receptor, simvastatin is less effective in this population. 9. Hypertriglyceridemia: Simvastatin has only a modest triglyceride-lowering effect and is not suitable for treating conditions characterized by elevated triglycerides, such as types I, IV, and V hyperlipidemia.
[Pediatric Use]
The safety and efficacy of simvastatin in patients aged 10-17 years with heterozygous familial hypercholesterolemia were evaluated in a controlled trial conducted in adolescent boys and girls (at least 1 year after menarche). Adverse events in patients treated with simvastatin were generally similar to those in the placebo group. No studies have been conducted in this population at doses greater than 40 mg. In this limited controlled study, simvastatin did not show significant effects on growth or sexual maturation in adolescent males or females, or on menstrual cycle length in adolescent females. (See Dosage and Administration; Adverse Reactions; Clinical Trials.) Adolescent females are advised to use appropriate contraceptive methods during simvastatin treatment. (See Contraindications; Precautions; Use in Pregnant and Lactating Women.) Simvastatin has not been studied in patients younger than 10 years of age or in premenarchal girls.
[Use in Elderly Patients]
In controlled clinical studies of simvastatin in elderly patients (>65 years), its effects on lowering total cholesterol and low-density lipoprotein cholesterol were similar to those seen in other populations, and there was no significant increase in the incidence of adverse reactions or laboratory abnormalities.
[Overdose]
There have been rare reports of overdoses; the maximum dose administered was 3.6 g. All patients recovered without sequelae. Conventional measures are generally used to manage overdose.
[Pharmacology and Toxicology]
Simvastatin can lower both normal and elevated low-density lipoprotein cholesterol (LDL-C) concentrations. LDL is formed from very low-density lipoprotein (VLDL) and is primarily catabolized through the high-affinity LDL receptor. The mechanisms by which simvastatin lowers LDL-C include: a decrease in VLDL-cholesterol concentrations, induction of LDL receptors, leading to a decrease in LDL cholesterol and increased LDL-C catabolism. Apolipoprotein B (apoB) levels also decrease significantly during simvastatin treatment. Since each LDL particle contains one molecule of apoB and apoB is rarely present in other lipoproteins, this suggests that simvastatin not only removes cholesterol from LDL but also reduces circulating LDL particle concentrations. Furthermore, simvastatin can increase high-density lipoprotein cholesterol (HDL-C) concentrations and lower plasma triglycerides (TG). All of these can lead to lowering of total cholesterol/HDL-C and LDL-C/HDL-C.
