Simvatin Tablet

Primary hypercholesterolemia (type IIa and IIb) in patients who have not responded adequately to diet and other appropriate measures. Coronary heart disease and elevated plasma cholesterol level.

Simvastatin is a preparation of Simvastatin which acts as a Cholesterol lowering agent. The main mechanism of reduction of low density lipoprotein (LDL) cholesterol is that following inhibition of HMG-CoA reductase activity, the LDL receptor density on the liver cells is increased and this leads to an increased removal of LDL cholesterol from the plasma and increased catabolism of LDL cholesterol. In addition, there is a reduction in the very low- density lipoprotein (VLDL) cholesterol and reduced formation of LDL from VLDL. Simvastatin is extensively metabolised in the liver; which is also the main site of action of the drug.

The patient should be placed on a standard cholesterol lowering diet before receiving Simvastatin and should continue on this during treatment with Simvastatin. The usual starting dose is 10 mg/day given as a single dose in the evening. Adjustment of dosage, if required, should be made at intervals of not less than four weeks, to a maximum of 40 mg daily given as a single dose in the evening. If LDL-cholesterol levels fall below 2 mmol/L or total plasma cholesterol levels fall below 3.5 mmol/L consideration should be given to reducing the dose of Simvastatin. In hypercholesterolemia, the recommended starting dose is 5-10 mg once a day in the evening and the recommended dosing range is 5-40 mg per day as a single dose in the evening. In patients with coronary heart disease and hypercholesterolemia, the starting dose should be 20 mg once a day in the evening. Because Simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with renal insufficiency. Safety and effectiveness in children and adolescents have not been established.

Digoxin: Concomitant administration of Simvatin and Digoxin in normal volunteers resulted in a slight elevation (less than 0.3 µgm/ml) in drug concentrations in plasma compared to concomitant administration of placebo and Digoxin.

Coumarin derivatives: Slightly enhance the anticoagulant effect of Warfarin (mean changes in p rothrombin time less than two seconds) in normal volunteers maintained in a state of low therapeutic anticoagulation.

Others: In clinical studies, Simvatin was used concomitantly with ACE inhibitors, beta-blockers, calcium channel blockers, diuretics and NSAIDs without evidence of clinically significant adverse interactions.

Simvastatin should not be used in-

• Active liver disease
• Pregnant and breast feeding mother
• Women of child bearing age unless they have been adequately protected by contraception
• Hypersensitivity to any component of the preparation
• Patients with the homozygous familial hypercholesterolemia who have a complete absence of LDL receptors

Simvatin is generally well tolerated. Headache, fatigue, insomnia, gastrointestinal effects like nausea, constipation or diarrhoea, flatulence, dyspepsia, abdominal cramps and muscular effects like myalgia, myositis and myopathy have been reported. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been associated with Simvatin therapy. Hepatitis, pancreatitis, rash, Angio-oedema have also been reported. No potentially life threatening effects have been reported.

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

• If there is a history of liver disease
• Who take high alcohol
• Liver function test should be done before and during treatment
• If serum transaminase rises three times the upper limit of normal, treatment should be discontinued
• Avoid pregnancy during and for one month after treatment

There are no data available on overdose. No antidote is available. General measures should be adopted and liver function should be monitored.

Other Anti-anginal & Anti-ischaemic drugs, Statins

Store in a cool, dry place, Away from light keep out of reach of children.