ZIMVA Tablet

As adjunct to diet for the reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia who have a significant risk of coronary artery disease and in patients with combined hypercholesterolemia and hypertriglyceridemia.

Dosage

Patients should be placed on standard cholesterol-lowering diet before receiving simvastatin and should remain on this diet during treatment with the drug.

Adults: Initial - Oral, 10-20mg once daily in the evening, the dosage being adjusted at 4 weeks intervals until the desired effect on lipoprotein concentration is observed, to a maximum of 80mg daily given as a single dose in the evening.

Maintenance - 5-80mg once daily in the evening.

Children: safety and efficacy have not been established.

In patients with known hypersensitivity to simvastatin or any component of the drug formulation or any HMG-CoA reductase inhibitor, active hepatic disease, in pregnancy, or in woman who is expected to be pregnant and in nursing woman.

The most common adverse effects are nausea, diarrhea, rash, dyspepsia, pruritus, alopecia, dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting and anemia.

Rarely rhabdomyolysis and hepatitis-jaundice occurred.

An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features; angioedema, lupus-like syndrome, polymyalgia rheumatic, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, ESR increased, arthritis, arthralgia, urticaria, photosensitivity, fever, flushing, dyspnea, and malaise.

1. Anticoagulants (coumarin or indandione-derivative): may increase bleeding or prothrombin time.

2. Cyclosporin, gemfibrozil, niacin, azole-derivative antifungal or macrolide antibiotic: may be associated with an increased risk of rhabdomyolysis and acute renal failure.

Contraindicated: See the package insert about the details.

1. This drug should be discontinued and physicians should be consulted if patients develop symptoms of muscle pain.

2. Liver function tests should be performed before treatment begins and 6 and 12 weeks thereafter. Patients who take this drug regularly should have LFTs semiannually or as recommended by physicians. It transaminase levels rise to >3 times the upper limit of normal, patients should stop taking the drug and consult a physician.

3. Caution should be exercised when statins are taken concomitantly with digoxin or warfarin because serum concentration of digoxin or warfarin will be elevated and may be harmful.

4. The risk of myopathy or rhabdomyolysis may be increased when concomitant use of statin drug with the following drugs: azole antifungals, e.g., ketoconazole, itraconazole etc., macrolide antibiotics, e.g., erythromycin, clarithromycin etc., HIV protease inhibitors, e.g., indinavir, nelfinavir, saquinavir etc., verapamil, diltiazem, gemfibrozil, nicotinic acid, cyclosporine, amiodarone etc.

5. The risk of rhabdomyolysis may be increased in patients who take higher doses, elderly, or patient with hepatic or renal impairment, alcoholism, hypothyroidism etc.

6. Caution is recommended when concomitantly used with colchicine, especially in elderly or patients with renal function impairment due to the risk of myopathy or rhabdomyolysis.

7. This drug may increase the risk of hyperglycemia.

PRECAUTIONS

1. Should be used with caution in patients who consume substantial amounts of alcohol and/or have a past history of liver disease.

2. Serum cholesterol and triglyceride concentration should be monitored prior to and regularly during medication.

3. If serum transaminase concentrations increase to 3 times the upper limit of normal and/or creatinine kinase concentrations are markedly increased or myositis occurs. Simvastatin should be discontinued.

Simvastatin is an antihyperlipidemic drug. Following absorption, Simvastatin is hydrolyzed to the beta-hydroxy acid active metabolite, in tissues. This active metabolite competitively inhibits the enzyme HMG-CoA reductase, the rate limiting step enzyme in cholesterol biosynthesis. The primary site of action of simvastatin is the liver. Inhibition of cholesterol synthesis leads to the upregulation of LDL receptors and an increase in catabolism of LDL cholesterol and reduction in LDL production. There may also be a slightly in high-density lipoprotein (HDL) concentrations.