Uses of Simastin: - High cholesterol - Prevention of heart attack and stroke Hyperlipidaemias, stroke prevention Acute liver disease or unexplained persistent elevations of serum transaminases. Patients of Chinese descent should not take simvastatin 80 mg/day w/ lipid-modifying dose of niacin-containing products (≥1 g). Simvastatin 80 mg should not be started in new patients and to those taking lower doses. Concurrent use w/ potent CYP3A4 inhibitors e.g. itraconazole, ketoconazole, posaconazole, clarithromycin, erythromycin, telithromycin, nefazodone, HIV protease inhibitors (e.g. nelfinavir), boceprivir, telaprevir., gemfibrozil, ciclosporin, danazol, grapefruit juice. Pregnancy and lactation.

Other Anti-anginal & Anti-ischaemic drugs, Statins

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.

How to use Simvastatin: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Simvastatin may be taken with or without food, but it is better to take it at a fixed time. Administration: May be taken with or without food. Adult Dose: Oral Hyperlipidaemias, Hypercholesterolemia Adult: Initially, 10-20 mg once daily. Patients w/ high CV risk or require a large reduction in cholesterol: Initially, 40 mg once daily. May adjust dose at intervals of at least 4 wk to max 80 mg once daily. All doses to be taken in the evening. Patients w/ homozygous familial hypercholesterolaemia: 40 mg once daily in the evening or 80 mg/day in 3 divided doses of 20 mg, 20 mg and an evening dose of 40 mg. Cardiovascular risk reduction Adult: High-risk patients (e.g. patients w/ DM or atherosclerotic CV disease): 20-40 mg once daily. Moderate-risk patients: 10 mg once daily. Dosage Modifications Coadministration with dronedarone, verapamil, or diltiazem: Do not exceed 10 mg/day Coadministration with amiodarone, amlodipine, or ranolazine: Do not exceed 20 mg/day Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter 80 mg/day should be used only for individuals who have been taking simvastatin 80 mg chronically (eg, >12 months) without evidence of myopathy or rhabdomyolysis Patients tolerating 80 mg who need to be initiated on an interacting drug that is contraindicated or associated with a maximum dose for simvastatin should be switched to an alternative statin with less potential for drug-drug interactions Patients unable to achieve their LDL-C goal utilizing 40 mg/day should not be titrated to 80 mg (increased risk for myopathy) but should instead be placed on alternative LDL-C-lowering treatment that provides greater LDL-C lowering Child Dose: Child Heterozygous familial hypercholesterolaemia: 10-17 yr Initially, 10 mg once daily May increase at intervals of 4 wk to max 40 mg/day. All doses to be taken in the evening. Hypercholesterolemia <10 years: Safety and efficacy not established Renal Dose: Renal impairment: Mild to moderate: No dosage adjustment needed. Severe: Initially, 5 mg once daily w/ close monitoring.

May increase bleeding risk w/ anticoagulants. Reduced serum levels w/ bosentan, efavirenz and rifampicin. Increased risk of myopathy and rhabdomyolysis w/ colchicine, amiodarone, verapamil and diltiazem. Increased risk of myopathy w/ amlodipine, fusidic acid. Potential reduction of cytotoxic effect of rituximab. Increased hepatotoxicity w/ ezetimibe. Potentially Fatal: Concurrent use w/ itraconazole, ketoconazole, posaconazole, clarithromycin, erythromycin, telithromycin, nefazodone, niacin, HIV protease inhibitors (e.g. nelfinavir), boceprivir, telaprevir, gemfibrozil, ciclosporin and danazol may increase the risk of myopathy, rhabdomyolysis and acute renal failure.

Acute liver disease or unexplained persistent elevations of serum transaminases. Patients of Chinese descent should not take simvastatin 80 mg/day w/ lipid-modifying dose of niacin-containing products (≥1 g). Simvastatin 80 mg should not be started in new patients and to those taking lower doses. Concurrent use w/ potent CYP3A4 inhibitors e.g. itraconazole, ketoconazole, posaconazole, clarithromycin, erythromycin, telithromycin, nefazodone, HIV protease inhibitors (e.g. nelfinavir), boceprivir, telaprevir., gemfibrozil, ciclosporin, danazol, grapefruit juice. Pregnancy and lactation.

Common - Abdominal pain - Constipation - Headache - Upper respiratory tract infection 1-10% CPK elevation (>3x ULN) (5%),Constipation (2%),Upper respiratory infection (9%),Flatulence (1-2%),Transaminases increased (>3x ULN) (1%),Headache (3-7%),Myalgia (5%),Eczema (5%),Vertigo (5%),Abdominal pain (7%) <1% Myalgia,Myopathy,Arthralgia,Arthritis,Eosinophilia,Chills,Angioedema,Rhabdomyolysis,Abdominal pain Potentially Fatal: Severe rhabdomyolysis with acute renal failure.

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.

Precaution: History of liver disease. Increased risk of rhabdomyolysis in severe infection, hypotension, major surgical trauma, uncontrolled seizures or severe metabolic, endocrine and electrolyte disorder. Alcoholism; premenarcheal females; children <10 yr. Discontinue treatment if there is marked or persistent increase in serum-aminotransferase concentrations. Monitoring Parameters Monitor creatine kinase (CK) periodically and LFT. Discontinue if there is significant or persistent increase in CK levels, serum aminotransferase levels or evidence of myopathy. Lactation: Contraindicated; potentially unsafe

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

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

Other Anti-anginal & Anti-ischaemic drugs, Statins

Simvastatin, an antilipemic agent is a competitive inhibitor of HMG-CoA reductase, the enzyme that catalyses the early and rate-limiting step in cholesterol biosynthesis reduces total cholesterol, LDL-cholesterol and triglycerides and increases HDL-cholesterol levels.

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.