SIMVASTATINTABLETS | Simvastatin
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahy-dro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ)). The molecular formula of simvastatin is CHO and its molecular weight is 418.57. Its structural formula is:
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Simvastatin tablets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg and 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, citric acid, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxides, isopropyl alcohol, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, talc and titanium dioxide.
Epidemiological studies have demonstrated that elevated levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), as well as decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Following an oral dose of C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (< 5%).
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.
The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. While the recommended therapeutic dose range is 5 to 80 mg/day, there was no substantial deviation from linearity of AUC of inhibitors in the general circulation with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal.
In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18 to 30 years of age. Clinical study experience in the elderly (n = 1522), suggests that there were no overall differences in safety between elderly and younger patients (see PRECAUTIONS, Geriatric Use).
Kinetic studies with another reductase inhibitor, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency (as measured by creatinine clearance).
In a study of 12 healthy volunteers, simvastatin at the 80 mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4.
The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Potent inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, Drug Interactions).
Gemfibrozil: Coadministration of gemfibrozil (600 mg twice daily for 3 days) with simvastatin (40 mg daily) resulted in clinically significant increases in simvastatin acid AUC (185%) and C (112%), possibly due to inhibition of simvastatin acid glucuronidation by gemfibrozil (see WARNINGS, Myopathy/Rhabdomyolysis, PRECAUTIONS, Drug Interactions, DOSAGE AND ADMINISTRATION).
Fenofibrate: Coadministration of fenofibrate (160 mg daily) with simvastatin (80 mg daily) for 7 days had no effect on plasma AUC (and C) of either total HMG-CoA reductase inhibitory activity or fenofibric acid; there was a modest reduction (approximately 35%) of simvastatin acid which was not considered clinically significant (see WARNINGS, Myopathy/Rhabdomyolysis, PRECAUTIONS, Drug Interactions).
Simvastatin is a substrate for CYP3A4 (see PRECAUTIONS, Drug Interactions). Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with, and 30 and 90 minutes following, a single dose of 60 mg simvastatin on the third day. This regimen of grapefruit juice resulted in mean increases in the concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [measured using a radioenzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 2.4-fold and 3.6-fold, respectively, and of simvastatin and its β-hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry] of 16-fold and 7-fold, respectively. In a second study, 16 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 20 mg simvastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [using a validated enzyme inhibition assay different from that used in the first study, both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 1.13-fold and 1.18-fold, respectively, and of simvastatin and its β-hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry] of 1.88-fold and 1.31-fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on simvastatin pharmacokinetics has not been studied.
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol 212 to 309 mg/dL (5.5 to 8 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20 to 40 mg/day (n = 2,221) or placebo (n = 2,223) for a median duration of 5.4 years. After six weeks of treatment with simvastatin the median (25th and 75th percentile) changes in LDL-C, TG, and HDL-C were -39% (-46, -31%), -19% (-31, 0%), and 6% (-3, 17%). Over the course of the study, treatment with simvastatin led to mean reductions in total-C, LDL-C and TG of 25%, 35%, and 10%, respectively, and a mean increase in HDL-C of 8%. Simvastatin significantly reduced the risk of mortality by 30% (p = 0.0003, 182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p = 0.00001, 111 vs 189 deaths). There was no statistically significant difference between groups in non-cardiovascular mortality. Simvastatin also significantly decreased the risk of having major coronary events (CHD mortality plus hospital-verified and silent non-fatal myocardial infarction [MI]) by 34% (p <0.00001, 431 vs 622 patients with one or more events). The risk of having a hospital-verified non-fatal MI was reduced by 37%.simvastatin significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (p <0.00001, 252 vs 383 patients). Furthermore, simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p = 0.033, 75 vs 102 patients). simvastatin reduced the risk of major coronary events to a similar extent across the range of baseline total and LDL cholesterol levels. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be adequately assessed. However, simvastatin significantly lessened the risk of having major coronary events by 34% (60 vs 91 women with one or more event). The randomization was stratified by angina alone (21% of each treatment group) or a previous MI. Because there were only 57 deaths among the patients with angina alone at baseline, the effect of simvastatin on mortality in this subgroup could not be adequately assessed. However, trends in reduced coronary mortality, major coronary events and revascularization procedures were consistent between this group and the total study cohort. Additionally, in this study, 1,021 of the patients were 65 and older. Cholesterol reduction with simvastatin resulted in similar decreases in relative risk for total mortality, CHD mortality, and major coronary events in these elderly patients, compared with younger patients.
The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on simvastatin 40 mg and 10,267 on placebo). Patients were allocated to treatment using a covariate adaptive method which took into account the distribution of 10 important baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients had a mean age of 64 years (range 40 to 80 years), were 97% Caucasian and were at high risk of developing a major coronary event because of existing coronary heart disease (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males 65 years of age and older (6%). At baseline, 3,421 patients (17%) had LDL-C levels below 100 mg/dL, of whom 953 (5%) had LDL-C levels below 80 mg/dL; 7,068 patients (34%) had levels between 100 and 130 mg/dL; and 10,047 patients (49%) had levels greater than 130 mg/dL.
The HPS results showed that simvastatin 40 mg/day significantly reduced: total and CHD mortality; non-fatal myocardial infarctions, stroke, and revascularization procedures (coronary and non-coronary) (see Table 1).
Two composite endpoints were defined in order to have sufficient events to assess relative risk reductions across a range of baseline characteristics (see Figure 1). A composite of major coronary events (MCE) was comprised of CHD mortality and non-fatal MI (analyzed by time-to-first event; 898 patients treated with simvastatin had events and 1,212 patients on placebo had events). A composite of major vascular events (MVE) was comprised of MCE, stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures (analyzed by time-to-first event; 2,033 patients treated with simvastatin had events and 2,585 patients on placebo had events). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p <0.0001). Furthermore, treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetics showed risk reductions for MCE and MVE due to simvastatin treatment regardless of baseline HbA1c levels or obesity with the greatest effects seen for diabetics without CHD.
Figure 1: The Effects of Treatment with Simvastatin on Major Vascular Events and Major Coronary Events in HPS
N = number of patients in each subgroup. The inverted triangles are point estimates of the relative risk, with their 95% confidence intervals represented as a line. The area of a triangle is proportional to the number of patients with MVE or MCE in the subgroup relative to the number with MVE or MCE, respectively, in the entire study population. The vertical solid line represents a relative risk of one. The vertical dashed line represents the point estimate of relative risk in the entire study population.
|Endpoint||Simvastatin(N = 10,269)n (%)†||Placebo (N = 10,267)n (%)†||Risk Reduction (%) (95% CI)||p-Value|
|Mortality||1,328 (12.9)||1,507 (14.7)||13(6 to 19)||p = 0.0003|
|CHD mortality||587 (5.7)||707 (6.9)||18(8 to 26)||p = 0.0005|
|Non-fatal MI||357 (3.5)||574 (5.6)||38(30 to 46)||p <0.0001|
|Stroke||444 (4.3)||585 (5.7)||25(15 to 34)||p <0.0001|
|Coronary revascularization||513 (5)||725 (7.1)||30(22 to 38)||p <0.0001|
|Peripheral and other non-coronary revascularization||450 (4.4)||532 (5.2)||16(5 to 26)||p = 0.006|
In the Multicenter Anti-Atheroma Study, the effect of simvastatin on atherosclerosis was assessed by quantitative coronary angiography in hypercholesterolemic patients with coronary heart disease. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were evaluated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. Simvastatin significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.
Simvastatin has been shown to be highly effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hypercholesterolemia and in mixed hyperlipidemia. A marked response was seen within 2 weeks, and the maximum therapeutic response occurred within 4 to 6 weeks. The response was maintained during chronic therapy. simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C (see Table 2).
In the Upper Dose Comparative Study, the mean reduction in LDL-C was 47% at the 80 mg dose. Of the 664 patients randomized to 80 mg, 475 patients with plasma TG ≤ 200 mg/dL had a median reduction in TG of 21%, while in 189 patients with TG > 200 mg/dL, the median reduction in TG was 36%. In these studies, patients with TG > 350 mg/dL were excluded.
Lower Dose Comparative Study
|Simvastatin5 mg q.p.m.||109||-19||-26||10||-12|
|Simvastatin10 mg q.p.m.||110||-23||-30||12||-15|
Scandinavian Simvastatin Survival Study
|Simvastatin20 mg q.p.m.||2221||-28||-38||8||-19|
Upper Dose Comparative Study
|Simvastatin 40 mg q.p.m.||433||-31||-41||9||-18|
|Simvastatin 80 mg q.p.m.||664||-36||-47||8||-24|
Multi-Center Combined Hyperlipidemia Study
|Simvastatin 40 mg q.p.m.||123||-25||-29||13||-28|
|Simvastatin80 mg q.p.m.||124||-31||-36||16||-33|
The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 3.
|Placebo||74||+2(-7, +7)||+1(-8, +14)||+3(-3, +10)||-9(-25, +13)||-7(-25, +11)||+1(-9, +8)|
|Simvastatin40 mg/day||74||-25(-34, -19)||-28(-40, -17)||+11(+5, +23)||-29(-43, -16)||-37(-54, -23)||-32(-42, -23)|
|80 mg/day||74||-32(-38, -24)||-37(-46, -26)||+15(+5, +23)||-34(-45, -18)||-41(-57, -28)||-38(-49, -32)|
The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG > 0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 4. In this study the median baseline values (mg/dL) were: total-C = 324, LDL-C = 121, HDL-C = 31, TG = 411, VLDL-C = 170, and non HDL-C = 291.
|TREATMENT||N||Total-C||LDL-C + IDL||HDL-C||TG||VLDL-C+IDL||Non-HDL-C|
|Placebo||7||-8(-24, +34)||-8(-27, +23)||-2(-21, +16)||+4(-22, +90)||-4(-28, +78)||-8(-26, -39)|
|Simvastatin 40 mg/day||7||-50(-66, -39)||-50(-60, -31)||+7(-8, +23)||-41(-74, -16)||-58(-90, -37)||-57(-72, -44)|
|Simvastatin 80 mg/day||7||-52(-55, -41)||-51(-57, -28)||+7(-5, +29)||-38(-58, +2)||-60(-72, -39)||-59(-61, -46)|
In a controlled clinical study, 12 patients 15 to 39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. Eleven of the 12 patients had reductions in LDL-C. In those patients with reductions, the mean LDL-C changes for the 40 and 80 mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80 mg dose.
In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other inhibitors of HMG-CoA reductase and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin (hCG). In another 24-week study, simvastatin 20 to 40 mg had no detectable effect on spermatogenesis. In 4S, in which 4,444 patients were randomized to simvastatin 20 to 40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadal axis in pre-menopausal women are unknown.
In a double-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10 to 17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (heFH) were randomized to simvastatin (n = 106) or placebo (n = 67) for 24 weeks (base study). Inclusion in the study required a baseline LDL-C level between 160 and 400 mg/dL and at least one parent with an LDL-C level > 189 mg/dL. The dosage of simvastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter. In a 24-week extension, 144 patients elected to continue therapy and received simvastatin 40 mg or placebo.
Simvastatin significantly decreased plasma levels of total-C, LDL-C, and Apo B (see Table 5). Results from the extension at 48 weeks were comparable to those observed in the base study.
After 24 weeks of treatment, the mean achieved LDL-C value was 124.9 mg/dL (range: 64to 289 mg/dL) in the simvastatin 40 mg group compared to 207.8 mg/dL (range: 128 to 334mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children with heterozygous familial hypercholesterolemia. The long-term efficacy of simvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
|Placebo||24 Weeks||67||% Change from Baseline(95% CI)||1.6(-2.2, 5.3)||1.1(-3.4, 5.5)||3.6(-0.7, 8)||-3.2(-11.8, 5.4)||-0.5(-4.7, 3.6)|
|Mean baseline, mg/dL (SD)||278.6(51.8)||211.9(49)||46.9(11.9)||90(50.7)||186.3(38.1)|
|Simvastatin||24 Weeks||106||% Change from Baseline (95% CI)||-26.5(-29.6, -23.3)||-36.8(-40.5, -33)||8.3(4.6, 1.9)||-7.9(-15.8, 0)||-32.4 (-35.9, -29)|
|Mean baseline, mg/dL (SD)||270.2(44)||203.8(41.5)||47.7(9)||78.3(46)||179.9(33.8)|
Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol (see National Cholesterol Education Program [NCEP] Treatment Guidelines, below).
In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet.
In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin is indicated to:
Simvastatin tablets are indicated to:
Simvastatin tablets are indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with heterozygous familial hypercholesterolemia, if after an adequate trial of diet therapy the following findings are present:
The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C < 130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined.
Prior to initiating therapy with simvastatin tablets, secondary causes for hypercholesterolemia (e.g., hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total-C, HDL-C, and TG. For patients with TG less than 400 mg/dL (< 4.5 mmol/L), LDL-C can be estimated using the following equation:
LDL-C = total-C – [(0.20 x TG) + HDL-C]
For TG levels > 400 mg/dL (> 4.5 mmol/L), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In many hypertriglyceridemic patients, LDL-C may be low or normal despite elevated total-C. In such cases, simvastatin tablets are not indicated.
Lipid determinations should be performed at intervals of no less than four weeks and dosage adjusted according to the patient's response to therapy.
The NCEP Treatment Guidelines are summarized in Table 6:
After the LDL-C goal has been achieved, if the TG is still ≥ 200 mg/dL, non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.
At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge.
The NCEP classification of cholesterol levels in pediatric patients with a familial history of either hypercholesterolemia or premature cardiovascular disease is summarized in Table 7.
Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the total-C be used to monitor therapy.
Simvastatin is indicated to reduce elevated LDL-C and TG levels in patients with Type IIb hyperlipidemia (where hypercholesterolemia is the major abnormality). However, it has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).
|Risk Category||LDL Goal (mg/dL)||LDL Level at Which to Initiate Therapeutic Lifestyle Changes (mg/dL)||LDL Level at Which to Consider Drug Therapy (mg/dL)|
||< 100||≥ 100||≥ 130 (100 to 129: drug optional)S
|2+ Risk factors (10-year risk ≤ 20%)||< 130||≥ 130||10-year risk 10 to 20%: ≥ 130 10-year risk <10%: ≥ 160|
|0 to 1 Risk factor
||< 160||≥ 160||≥ 190 (160 to 189: LDL-lowering drug optional)|
|Category||Total-C (mg/dL)||LDL-C (mg/dL)|
|U.S. National Library of Medicine|
Drugs and Medications
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use simvastatin safely and effectively. See full prescribing information for simvastatin tablets. Si...
These highlights do not include all the information needed to use simvastatin safely and effectively. See full prescribing information for simvastatin tablets. Simvastatin Tablets, USP Initial U.S. Ap...
SIMVASTATIN ORALLY DISINTEGRATING TABLETS(SIMVASTATIN)
These highlights do not include all the information needed to use simvastatin safely and effectively. See full prescribing information for simvastatin tablets. Simvastatin Tablets, USP Initial U.S. Ap...
These highlights do not include all the information needed to use simvastatin safely and effectively. See full prescribing information for simvastatin tablets, USP. Simvastatin Tablets, USP Initial U....
This study will assess whether co-administration of ezetimibe 10 mg with simvastatin 20 mg will be more effective than treatment with simvastatin 20 mg alone in reducing LDL-C concentratio...
Both simvastatin 40 mg and simvastatin/ezetimibe 10/10 mg result in LDL-C reductions of approximately the same magnitude. However, the differential effects of these two treatment options o...
The purpose of this study is to determine whether, in patients with chronic proteinuric nephropathy and dyslipidemia, ezetimibe-simvastatin combined therapy is more effective than statin a...
To investigate the effect of multiple doses of SLV337 on the pharmacokinetics of simvastatin and simvastatin acid when co-administered in healthy male subjects
The purpose of this study is to evaluate whether coadministration of ezetimibe 10 mg/day with simvastatin 20 mg/day for 12 weeks will result in greater reduction of LDL-C, total cholestero...
In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alon...
Abstract:：To prepare ethosome loading simvastatin,an orthogonal test was applied to optimize the prescriptions, and the qualities of simvastatin ethosome were characterized by the shape, particle si...
We have prospectively tested the effects of simvastatin on the pharmacokinetics of anastrozole and on estrogen concentrations in postmenopausal women with hormone receptor-positive breast cancer who w...
ABSTRACT: BACKGROUND: Treatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have d...
Biotech & Healthcare Channels World News Life Science Events Corporate Database Market Reports Categories
Clinical Trials - Daily Updated Database search the latest medical and pharmaceutical trials.
Drugs Database search our comprehensive database of prescription drugs.
Research Literature - Daily Updated Database search biomedical papers and journals.
Drugs and Medication Quicklinks
Searches Linking to this Drug Record
denticare/ 2%neutral /sodium fluoride gel.msds, medicom denti care denti rinse buy, clinical effectiveness of neutral sodium fluoride, denticare chx rinse msds, denticare fluoride rinse msds, Denticare 2% Neutral Sodium Fluoride Rinse msds, neutral flouride rinse, neutral flouride rinse, medicom Denti-care Denti-rinse msds, medicom Denti-care Denti-rinse msds, denti-care denti-rinse, denti-care denti-rinse, Denti-Care 2% Sodium Fluoride Rinse MSDS, 2% neutral sodium fluoride oral rinse, fluoride 2% Neutral sodium msds denticare