Covastin Film-Coated Tablets 10mg:
Each tablet contains Simvastatin U.S.P. 10 mg
Covastin Film-Coated Tablets 20mg:
Each tablet contains Simvastatin U.S.P. 20 mg
Covastin Film-Coated Tablets 40mg:
Each tablet contains Simvastatin U.S.P. 40 mg
MODE OF ACTION
Simvastatin, which is an inactive lactone, is hydrolyzed to
the corresponding β-hydroxyacid form after oral ingestion.
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.
Covastin reduces both normal and elevated low-density
lipoprotein cholesterol (LDL-C) concentrations in plasma.
LDL is formed from very-low-density lipoprotein (VLDL) and
is catabolized predominantly by the high-affinity LDL
receptor on hepatocyte membranes. The mechanism of the
LDL-lowering effect of simvastatin may involve both
reduction of VLDL cholesterol (VLDL-C) concentration, and
induction of the LDL receptor, leading to reduced production
and/or increased catabolism of LDL-C. In addition, Covastin
also reduces VLDL-C and triglycerides (TG) and increases
high-density lipoprotein cholesterol (HDL-C) concentrations.
Simvastatin is absorbed from the gastrointestinal tract and
is hydrolysed to its active β-hydroxyacid form. Other active
metabolites have been detected and a number of inactive
metabolites are also formed.
Simvastatin undergoes extensive first-pass metabolism in
the liver, its primary site of action, with subsequent excretion
of drug equivalents in the bile. As a consequence of
extensive hepatic extraction of simvastatin, the availability
of active metabolites of an oral dose to the general circulation
is low, reported to be less than 5%.
Both simvastatin and its β-hydroxyacid metabolite are highly
bound (approximately 95%) to human plasma proteins.
Peak plasma concentration of β-hydroxyacid metabolites
was attained within 1.3 to 2.4 hours postdose.
Simvastatin is mainly excreted in the feces via the bile as
metabolites. About 10 to 15% is recovered in the urine,
mainly in inactive forms.
Therapy with lipid-altering agents should be considered in
those individuals at increased risk for atherosclerosis-related
clinical events as a function of cholesterol level, the presence
of congestive heart failure, or other risk factors. Covastin
is used when the response to a saturated fat and cholesterol-
restricted diet and other non-pharmacological measures
alone has been inadequate.
Coronary Heart Disease
In patients with coronary heart disease and
hypercholesterolemia, Covastin is indicated to:
Reduce the risk of total mortality by reducing coronary
Reduce the risk of non-fatal myocardial infarction.
Reduce the risk for undergoing myocardial
revascularization procedures (coronary artery bypass
grafting and percutaneous transluminal coronary
Slow the progression of coronary atherosclerosis,
including reducing the development of new lesions and
new total occlusions.
Covastin is indicated as an adjunct to diet for reduction of
elevated total-cholesterol, LDL-C, apolipoprotein B (Apo B),
and TG in patients with primary hypercholesterolemia,
heterozygous familial hypercholesterolemia or combined
(mixed) hyperlipidemia when response to diet and other
nonpharmacological measures is inadequate. Covastin also
raises HDL-C and therefore lowers the LDL/HDL and total