Simvastatin

 

Pharmacokinetics

  


Simvastatin is absorbed from the gastrointestinal tract and is
hydrolysed to its active beta-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. Less than 5% of the oral dose has been reported
to reach the circulation as active metabolites. Both simvastatin and its
beta-hydroxyacid metabolite are about 95% bound to plasma proteins. It
is mainly excreted in the faeces via the bile as metabolites. About 10
to 15% is recovered in the urine, mainly in inactive forms. The
half-life of the active metabolite is 1.9 hours.

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Indication
& Dosage

 


Oral

HYPERCHOLESTEROLEMIA WITH I.H.D; HYPERCHOLESTEROLEMIA IN TYPE IIa AND
TYPE IIb HPERLIPOROTEINEMIAS; COMINED HYPERTRIGLYCERIDEMIA AND
HYPERCHOLESTEROLEMAIA: Initially 5-10mg OD in the evening. Max dose
40mg/day. Dosage individualized and dose adjustments made at intervals
of 4 weeks or more.

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Action

 


It is a prodrug which gets bioactivated in the liver to form the
active beta-hydroxyacid derivative. This inhibits the conversion of HMG-Co
A to mevalonic acid  by blocking the enzyme HMG-Co A reductase, an
early and rate limiting step in the biosynthesis of cholesterol.
Simvastatin has been demonstrated to reduce total cholesterol, LDL-cholesterol,
and triglycerides by 25%, 35% and 10% respectively; increase in HDL is
upt 12%. Major trials have documented simvastatin’s beneficial role in
substatially reducing both cardiovascular morbidity and mortality.

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Interaction

 

There is an increased risk of myopathy if certain drugs such as
immunosuppressants (notably cyclosporin), fibric acid derivatives, or
nicotinic acid are given concurrently with statins; for further details
see Effects on Skeletal Muscle, under Adverse Effects. Bleeding and
increases in prothrombin time have been reported in patients taking
simvastatin with coumarin anticoagulants. Raised concentrations of
simvastatin have occurred in patients also given mibefradil.

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Adverse
Effect & Precautions





Constipation, diarrhoea, nausea,
dyspepsia, flatulence, dizziness, skin rash, fatigue, myopathy.



Precaution: Past history of liver disease, in patients who consume
substantial quantities of alcohol, renal failure, severe acute
infection. major surgery, trauma, electrolyte disorders and uncontrolled
seizures. Liver function tests should be performed during therapy with
simvastatin. Patients should be advised to report any unexplained muscle
pain, tenderness, particularly if accompained by malaise or fever.

Pregnancy: Contraindicated.

Breast Feeding: COntraindicated.

Man: Use with caution.

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Brands
available in market

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