DESCRIPTION
id: f6bb6943-b1b2-4cfb-b34b-02e2a43b9fb7
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahy-dro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ]]. The molecular formula of simvastatin is C25H38O5 and its molecular weight is 418.57. Its structural formula is:
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Simvastatin tablets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg and 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, citric acid, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxides, isopropyl alcohol, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, talc and titanium dioxide.
CLINICAL PHARMACOLOGY
id: 752f3217-8828-47cd-8de1-4e507fe2e94d
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
Epidemiological studies have demonstrated that elevated levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), as well as decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
INDICATIONS AND USAGE
id: a1ed219b-5cf1-49ee-a690-cbdbaf15d0cd
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol (see National Cholesterol Education Program [NCEP] Treatment Guidelines, below).
In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet.
CONTRAINDICATIONS
id: 937e7117-18ce-4d59-8302-55c71266a248
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Hypersensitivity to any component of this medication.
Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS).
Pregnancy and lactation. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as simvastatin to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, simvastatin is contraindicated during pregnancy and in nursing mothers. Simvastatin
should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see PRECAUTIONS, Pregnancy).
ADVERSE REACTIONS
id: 6cba0cd9-f1d3-4b8c-acea-0cb21b34a3ea
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with mean duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse experiences attributable to simvastatin. Adverse reactions have usually been mild and transient. simvastatin has been evaluated for serious adverse reactions in more than 21,000 patients and is generally well tolerated.
OVERDOSAGE
id: 4192faf9-4586-440d-b9bc-c3298d082c0c
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.
A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae. Until further experience is obtained, no specific treatment of overdosage with simvastatin can be recommended.
The dialyzability of simvastatin and its metabolites in man is not known at present.
DOSAGE AND ADMINISTRATION
id: 50cff537-b5aa-43ae-9410-440a806cd520
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
The patient should be placed on a standard cholesterol-lowering diet. In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet. The dosage should be individualized according to the goals of therapy and the patient’s response. (For the treatment of adult dyslipidemia, see NCEP Treatment Guidelines. For the reduction in risks of major coronary events, see CLINICAL PHARMACOLOGY, Clinical Studies in Adults.) The dosage range is 5-80 mg/day (see below).
The recommended usual starting dose is 20 to 40 mg once a day in the evening. For patients at high risk for a CHD event due to existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter. See below for dosage recommendations in special populations (i.e., homozygous familial hypercholesterolemia, adolescents and renal insufficiency) or for patients receiving concomitant therapy (i.e., cyclosporine, danazol, amiodarone, verapamil, or gemfibrozil).
HOW SUPPLIED
id: b1930dfb-5be1-4b6e-be5d-6ebbf6601eb4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Simvastatin Tablets 5 mg are peach colored, round, film-coated tablets, debossed RX6 on one side and plain on the other side.
Simvastatin Tablets 10 mg are peach colored, round, film-coated tablets, debossed RX790 on one side and plain on the other side.
Simvastatin Tablets 20 mg are tan colored, round, film-coated tablets, debossed RX791 on one side and plain on the other side.
Simvastatin Tablets 40 mg are brick red colored, round, film-coated tablets, debossed RX792 on one side and plain on the other side.
Simvastatin Tablets 80 mg are brick red colored, round, film-coated tablets, debossed RX793 on one side and plain on the other side.
They are supplied by State of Florida DOH Central Pharmacy as follows:
|
NDC
|
Strength
|
Quantity/Form
|
Color
|
Source Prod. Code
|
| 53808-0793-1 |
20 mg |
30 Tablets in a Blister Pack |
Tan color |
63304-791 |
Storage
Store at 20 – 25° C (68 – 77° F). (See USP Controlled Room Temperature).
Manufactured for:
Ranbaxy Pharmaceuticals Inc.
Jacksonville, FL 32257 USA
This Product was Repackaged By:
State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States
Label Image for 20mg
id: 4db6e91d-f956-4547-8561-51d1652fb464
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
