INDICATIONS AND USAGE
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 Orally Disintegrating Tablets can be started simultaneously with diet.
Reductions in Risk of CHD Mortality and Cardiovascular Events
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 Orally Disintegrating Tablets are indicated to:Reduce the risk of total mortality by reducing CHD deaths.Reduce the risk of non-fatal myocardial infarction and stroke.Reduce the need for coronary and non-coronary revascularization procedures.
Patients with Hypercholesterolemia Requiring Modifications of Lipid Profiles
Simvastatin Orally Disintegrating Tablets are indicated to:Reduce elevated total-C, LDL-C, Apo B, and TG, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIbClassification of Hyperlipoproteinemias
TypeLipoproteinselevatedLipid Elevations
majorminor
C = cholesterol, TG = triglycerides,
LDL = low-density lipoprotein,
VLDL = very-low-density lipoprotein
IDL = intermediate-density lipoprotein
I (rare)chylomicronsTG
C
IIaLDLC
IIbLDL, VLDLCTG
III (rare)IDLC/TG
IVVLDLTG
C
V (rare)chylomicrons, VLDLTG
C
).Treat patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia).Treat patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH)
Simvastatin Orally Disintegrating 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, 10-17 years of age, with heterozygous familial hypercholesterolemia, if after an adequate trial of diet therapy the following findings are present:1.LDL cholesterol remains 190 mg/dL; or2.LDL cholesterol remains 160 mg/dL andThere is a positive family history of premature cardiovascular disease (CVD) orTwo or more other CVD risk factors are present in the adolescent patient.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.
General Recommendations
Prior to initiating therapy with simvastatin, 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
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 Orally Disintegrating 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:TABLE 6
NCEP Treatment Guidelines:LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changesand Drug Therapy in Different Risk Categories
Risk CategoryLDL Goal (mg/dL)LDL Level at Which to Initiate Therapeutic Lifestyle Changes (mg/dL)LDL Level at Which to Consider Drug Therapy (mg/dL)
CHDCHD, coronary heart disease or CHD risk equivalents (10-year risk >20%)<100100130(100-129: drug optional)Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory.
2+ Risk factors(10-year risk 20%)<13013010-year risk 10-20%: 13010-year risk <10%: 160
0-1 Risk factorAlmost all people with 0-1 risk factor have a 10-year risk <10%; thus, 10-year risk assessment in people with 0-1 risk factor is not necessary.<160160190(160-189: LDL-lowering drug optional)
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.TABLE 7
NCEP Classification of Cholesterol Levels in Pediatric Patients with a Familial History of Either HeFH or Premature CVD
CategoryTotal-C (mg/dL)LDL-C (mg/dL)
Acceptable<170<110
Borderline170-199110-129
High200130
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 Orally Disintegrating Tablets are 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).