Description

Antichol (simvastatin) is a lipid-lowering agent derived synthetically from a fermentation product of Aspergillus terreus.
After oral ingestion, Antichol, an inactive lactone, is hydrolyzed to the corresponding •-hydroxyacid form. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes an early and rate-limiting step in the biosynthesis of cholesterol. Clinical studies show Antichol to be highly effective in reducing total plasma cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), triglycerides(TG), and very low density lipoprotein cholesterol (VLDL-C) concentrations, and increasing high-density lipoprotein cholesterol (HDL-C), in heterozygous familial and non familial forms of hypercholesterolemia,and in mixed hyperlipidemia, when elevated cholesterol was cause for concern and diet alone has been insufficient. Marked responses are seen within 2 weeks, and maximum therapeutic responses occur within 4-6 weeks. The response is maintained during continuation of therapy. When therapy with Antichol is stopped, cholesterol and lipids return to pretreatment levels. The active form of simvastatin is a specific inhibitor of HMG-CoA reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. Because the conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway of cholesterol, therapy with Antichol would not be expected to cause an accumulation of potentially toxic sterols. In addition, HMG-CoA is also metabolized readily back to acetyl-CoA, which participates in many biosynthetic processes in the body.

Presentation:
Antichol 10 : Pack of 1 x 10’s tablets.
Antichol 20 : Pack of 1 x 10’s tablets.

Composition:
Antichol 10 :
Each film coated tablet contains simvastatin USP ............. 10 mg.

Antichol 20 :
Each film coated tablet contains simvastatin USP ............. 20 mg.

Indications:
Coronary Heart Disease;
In patients with coronary heart disease, Antichol is indicated to:
Reduce the risk of death.
Reduce the risk of coronary death and non-fatal myocardial infarction.
Reduce the risk of stroke and transient ischemic attacks.(TIA)
Reduce the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty);
Slow the progression of coronary atherosclerosis, including reducing the development of new lesions and new total occlusions.

Hyperlipidemia;

Antichol is indicated as an adjunct to diet to reduce elevated total -C, LDL-C, TG, and apolipoprotein B (apo B) and to increase HDL-C in patients with primary hypercholesterolemia including heterozygous familial hypercholesterolemia (Fredrickson type IIa) or combined (mixed) hyperlipidemia (Fredrickson type llb), when response to diet and other nonpharmacological measures is inadequate. Antichol, therefore, lowers LDL-C/HDL-C and total-C/HDL-C ratios.

Antichol is indicated for the treatment of patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia).

Antichol is indicated for the treatment of patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia).

Antichol is also indicated as an adjunct to diet and other non-dietary measures for the treatment of patients with homozygous familial hypercholesterolemia to reduce elevated total-C, LDL-C and apo B.

Dosage and Administration:
The patients should be placed on a standard cholesterol- lowering diet before receiving Antichol and should continue on this diet during treatment with Antichol.

Coronary Heart Disease:
Patients with CHD can be treated with a starting dose of 20 mg/day given as a single dose in the evening. Adjustments of dosage, if required, should be made at intervals of not less than 4 weeks, to a maximum of 80 mg /day given as a single dose in the evening .

Hyperlipidemia:
The usual starting dose is 10mg/day given as a single dose in the evening, Patients with mild to moderate hypercholesterolemia can be treated with a starting dose of 5 mg of Antichol. Adjustment of dosage, if required, should be made as specified above.

Homozygous familial Hypercholesterolemia:
Based on the results of a controlled clinical study, the recommended dosage for patients with homozygous familial hypercholesterolemia is Antichol 40 mg/day in the evening or 80mg/day, in 3 divided doses of 20 mg, 20 mg and 40 mg in the evening.

Concomitant Therapy:
Antichol is effective alone or in combination with bile acid sequestrants.
In patients taking cyclosporine, fibrates or niacin concomitantly with Antichol, the maximum recommended dosage is 10mg/day.

Dosage in renal insufficiency:
Because Antichol does not undergo significant renal excretion, modification of dosage should not be necessary in patients with moderate renal insufficiency.
In patients with severe renal insufficiency (creatinine clearance <30ml/min), dosages above 10mg/day should be carefully considered and, if deemed necessary, implemented, cautiously.

Side Effects:
Gastrointestinal: Abdominal pain, constipation, flatulence, nausea, diarrhoea, dyspepsia, vomiting, pancreatitis.
C.N.S.: Paraesthesia, peripheral neuropathy, dizziness, headache.
Generals: Asthenia, myopathy, muscle cramps, myalgia, urticaria, alopecia.

Contraindications:
Hypersensitivity to any component of this preparation. Active liver disease or unexplained persistent elevations of serum transaminases. Pregnancy and nursing.

Cautions:
Muscle Effects:
Simvastatin and other inhibitors of HMG-CoA reductase occasionally caused myopathy, which is manifested as muscle pain or weakness associated with grossly elevated creatine kinase (CK).
Rhabdomyolysis, with or without acute renal failure, secondary myoglobinuria, has been reported rarely.

Hepatic Effects:
In clinical studies, persistent increases (to more than 3xULN) in serum transaminases have occurred in a few adult patients who received simvastatin. When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels.
It is recommended that LFTs be performed before treatment begins and periodically thereafter, in all patients. If the transaminase levels show evidence of progression and are persistent, the drug should be discontinued.

Use in Pregnancy and Lactation:
Antichol is contraindicated during pregnancy.
It is not known whether simvastatin or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions, women taking Antichol should not breast feed their infants.

Drug Interactions:
Gemfibrozil and other fibrates, lipid lowering-doses, (> 1g /day) of niacin increase the risk of myopathy when given concomitantly with simvastatin, probably because they can produce myopathy when given alone.
Simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants as a result the P.T. reported as I.N.R. increased respectively .

Over Dosage:
A few cases of overdosage have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 450 mg . General measures should be adopted.

Storage:
Store below 30 C.
Protect from heat & moisture.