PRAVASTATIN SODIUM TABLETS, Rx only

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Pravastatin sodium is one of a class of lipid-lowering compounds, the HMG-CoA reductase inhibitors, which reduce cholesterol biosynthesis. These agents are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme catalyzing the early rate-limiting step in cholesterol biosynthesis, conversion of HMG-CoA to mevalonate. Pravastatin sodium is designated chemically as 1-naphthaleneheptanoic acid, 1,2,6,7,8,8a-hexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, monosodium salt, [1S-[1α (βS*,δS*),2α,6α,8β(R*),8aα]]-. It has the following structural formula: C₂₃ H₃₅ NaO₇ M.W. 446.52 Pravastatin sodium is an odorless, white to off-white, fine or crystalline powder. It is a relatively polar hydrophilic compound with a partition coefficient (octanol/water) of 0.59 at a pH of 7.0. It is soluble in methanol and water (> 300 mg/mL), slightly soluble in isopropanol, and practically insoluble in acetone, acetonitrile, chloroform, and ether. Pravastatin sodium tablets are available for oral administration as 10 mg, 20 mg, and 40 mg tablets. Inactive ingredients include: calcium phosphate dibasic, croscarmellose sodium, crospovidone, lactose, microcrystalline cellulose, povidone, and sodium stearyl fumarate. The 10 mg tablet also contains ferric oxide red, the 20 mg tablet also contains ferric oxide yellow, and the 40 mg tablet also contains Yellow DC No. 10 and FDC Blue No. 1.

CLINICAL PHARMACOLOGY

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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Cholesterol and triglycerides in the bloodstream circulate as part of lipoprotein complexes. These complexes can be separated by density ultracentrifugation into high (HDL), intermediate (IDL), low (LDL), and very low (VLDL) density lipoprotein fractions. Triglycerides (TG) and cholesterol synthesized in the liver are incorporated into very low density lipoproteins (VLDLs) and released into the plasma for delivery to peripheral tissues. In a series of subsequent steps, VLDLs are transformed into intermediate density lipoproteins (IDLs), and cholesterol-rich low density lipoproteins (LDLs). High density lipoproteins (HDLs), containing apolipoprotein A, are hypothesized to participate in the reverse transport of cholesterol from tissues back to the liver. Pravastatin sodium produces its lipid-lowering effect in two ways. First, as a consequence of its reversible inhibition of HMG-CoA reductase activity, it effects modest reductions in intracellular pools of cholesterol. This results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL. Second, pravastatin inhibits LDL production by inhibiting hepatic synthesis of VLDL, the LDL precursor. Clinical and pathologic studies have shown that elevated levels of total cholesterol (Total-C), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB – a membrane transport complex for LDL) promote human atherosclerosis. Similarly, decreased levels of HDL-cholesterol (HDL-C) and its transport complex, apolipoprotein A, are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of Total-C and LDL-C and inversely with the level of HDL-C. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including VLDL, IDL, and remnants, can also promote atherosclerosis. Elevated plasma TG are frequently found in a triad with low HDL-C levels and small LDL particles, as well as in association with non-lipid metabolic risk factors for coronary heart disease. As such, total plasma TG has not consistently been shown to be an independent risk factor for CHD. Furthermore, the independent effect of raising HDL or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined. In both normal volunteers and patients with hypercholesterolemia, treatment with pravastatin sodium tablets reduced Total-C, LDL-C, and apolipoprotein B. Pravastatin sodium also reduced VLDL-C and TG and produced increases in HDL-C and apolipoprotein A. The effects of pravastatin on Lp (a), fibrinogen, and certain other independent biochemical risk markers for coronary heart disease are unknown. Although pravastatin is relatively more hydrophilic than other HMG-CoA reductase inhibitors, the effect of relative hydrophilicity, if any, on either efficacy or safety has not been established. In one primary (West of Scotland Coronary Prevention Study – WOS)¹ prevention study, pravastatin has been shown to reduce cardiovascular morbidity and mortality across a wide range of cholesterol levels (see Clinical Studies).

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Therapy with pravastatin sodium tablets should be considered in those individuals at increased risk for atherosclerosis-related clinical events as a function of cholesterol level, the presence or absence of coronary heart disease, and other risk factors.

CONTRAINDICATIONS

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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).

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Pravastatin is generally well tolerated; adverse reactions have usually been mild and transient. In 4 month-long placebo-controlled trials, 1.7% of pravastatin-treated patients and 1.2% of placebo-treated patients were discontinued from treatment because of adverse experiences attributed to study drug therapy; this difference was not statistically significant. (See also PRECAUTIONS, Geriatric Use).

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

To date, there has been limited experience with overdosage of pravastatin. If an overdose occurs, it should be treated symptomatically with laboratory monitoring and supportive measures should be instituted as required. (See WARNINGS).

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The patient should be placed on a standard cholesterol-lowering diet before receiving pravastatin sodium and should continue on this diet during treatment with pravastatin (see NCEP Treatment Guidelines for details on dietary therapy). Pravastatin can be administered orally as a single dose at any time of the day, with or without food. Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed at this time and dosage adjusted according to the patient’s response to therapy and established treatment guidelines.

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Pravastatin sodium tablets are supplied as: 10 mg tablets: Pink, unscored, round tablet, debossed “93” on one side and “771” on the other side. 20 mg tablets: Light yellow, unscored, round tablet, debossed “93” on one side and “7201” on the other side. 40 mg tablets: Light green, unscored, round tablet, debossed “93” on one side and “7202” on the other side. They are supplied by State of Florida DOH Central Pharmacy as follows:

REFERENCES

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displayName: REFERENCES SECTION
FDA Article Code: 34093-5

Shepherd J, et al. Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia (WOS). N Engl J Med 1995;333:1301-7.
Pitt B, et al. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I): Reduction in Atherosclerosis Progression and Clinical Events. J Am Coll Cardiol 1995;26:1133-9.
Jukema JW, et al. Effects of Lipid Lowering by Pravastatin on Progression and Regression of Coronary Artery Disease in Symptomatic Man With Normal to Moderately Elevated Serum Cholesterol Levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation 1995; 91:2528-2540.
Crouse JR, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries: Design Features of a Clinical Trial with Carotid Atherosclerosis Outcome (PLAC II). Controlled Clinical Trials 1992;13:495.
Salonen R, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A Population-based Primary Preventive Trial of the Effect of LDL Lowering on Atherosclerotic Progression in Carotid and Femoral Arteries. Research Institute of Public Health, University of Kuopio, Finland. Circulation 1995;92:1758.
Fredrickson DS, et al. Fat Transport in Lipoproteins-An Integrated Approach to Mechanisms and Disorders. N Engl J Med 1967; 276:34-42, 94-102, 148-156, 215-224, 273-281.
Manson JM, Freyssinges C, Ducrocq MB, Stephenson WP. Postmarketing Surveillance of Lovastatin and Simvastatin Exposure During Pregnancy. Reproductive Toxicology 1996;10(6):439-446.

10mg Label

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

20mg Label

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

40mg Label

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4