PRAVASTATIN SODIUM

Contraindications, Pregnancy and Lactation Removed (4) 05/2022 Warnings and Precautions, Immune-Mediated Necrotizing Myopathy Updated (5.2) 05/2022 Contraindications, Pregnancy and Lactation Removed ( 4 ) 05/2022 Warnings and Precautions, Immune-Mediated Necrotizing Myopathy Updated ( 5.2 ) 05/2022

1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. Pravastatin Sodium is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce the risk of MI, revascularization, and cardiovascular mortality in hypercholesterolemic patients without clinically evident CHD. (1.1) Reduce the risk of total mortality by reducing coronary death, MI, revascularization, stroke/TIA, and the progression of coronary atherosclerosis in patients with clinically evident CHD. (1.1) Reduce elevated Total-C, LDL-C, ApoB, and TG levels and to increase HDL­ C in patients with primary hypercholesterolemia and mixed dyslipidemia. (1.2) Reduce elevated serum TG levels in patients with hypertriglyceridemia. (1.2) Treat patients with primary dysbetalipoproteinemia who are not responding to diet. (1.2) Treat children and adolescent patients ages 8 years and older with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (1.2) Limitations of use: Pravastatin sodium has not been studied in Fredrickson Types I and V dyslipidemias. (1.3) 1.1 Prevention of Cardiovascular Disease In hypercholesterolemic patients without clinically evident coronary heart disease (CHD), Pravastatin Sodium is indicated to: reduce the risk of myocardial infarction (MI). reduce the risk of undergoing myocardial revascularization procedures. reduce the risk of cardiovascular mortality with no increase in death from non-cardiovascular causes. In patients with clinically evident CHD, Pravastatin Sodium is indicated to: reduce the risk of total mortality by reducing coronary death. reduce the risk of MI reduce the risk of undergoing myocardial revascularization procedures. reduce the risk of stroke and stroke/transient ischemic attack (TIA). slow the progression of coronary atherosclerosis. 1.2 Hyperlipidemia Pravastatin Sodium is indicated: as an adjunct to diet to reduce elevated total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and triglyceride (TG) levels and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia ( Fredrickson Types IIa and IIb). 1 as an adjunct to diet for the treatment of patients with elevated serum TG levels ( Fredrickson Type IV). for the treatment of patients with primary dysbetalipoproteinemia ( Fredrickson Type III) who do not respond adequately to diet. as an adjunct to diet and lifestyle modification for treatment of heterozygous familial hypercholesterolemia (HeFH) in children and adolescent patients ages 8 years and older if after an adequate trial of diet the following findings are present: a. LDL-C remains ≥190 mg/dL or b. LDL-C remains ≥160 mg/dL and: there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors are present in the patient. 1.3 Limitations of Use Pravastatin Sodium has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons ( Fredrickson Types I and V).

1.1 Prevention of Cardiovascular Disease In hypercholesterolemic patients without clinically evident coronary heart disease (CHD), Pravastatin Sodium is indicated to: reduce the risk of myocardial infarction (MI). reduce the risk of undergoing myocardial revascularization procedures. reduce the risk of cardiovascular mortality with no increase in death from non-cardiovascular causes. In patients with clinically evident CHD, Pravastatin Sodium is indicated to: reduce the risk of total mortality by reducing coronary death. reduce the risk of MI re …

2 DOSAGE AND ADMINISTRATION Adults: the recommended starting dose is 40 mg once daily. Use 80 mg dose only for patients not reaching LDL-C goal with 40 mg. (2.2) Significant renal impairment: the recommended starting dose is pravastatin 10 mg once daily. (2.3) Children (ages 8 to 13 years, inclusive): the recommended starting dose is 20 mg once daily. (2.4) Adolescents (ages 14 to 18 years): the recommended starting dose is 40 mg once daily. (2.4) 2.1 General Dosing Information 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 Sodium [see NCEP Treatment Guidelines for details on dietary therapy]. 2.2 Adult Patients The recommended starting dose is 40 mg once daily. If a daily dose of 40 mg does not achieve desired cholesterol levels, 80 mg once daily is recommended. Pravastatin Sodium 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. 2.3 Patients with Renal Impairment In patients with severe renal impairment, a starting dose of 10 mg pravastatin daily is recommended. 2.4 Pediatric Patients Children (Ages 8 to 13 Years, Inclusive) The recommended dose is 20 mg once daily in children 8 to 13 years of age. Doses greater than 20 mg have not been studied in this patient population. Adolescents (Ages 14 to 18 Years) The recommended starting dose is 40 mg once daily in adolescents 14 to 18 years of age. Doses greater than 40 mg have not been studied in this patient population. Children and adolescents treated with pravastatin should be reevaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C [see Indications and Usage (1.2) ]. 2.5 Concomitant Lipid-Altering Therapy Pravastatin Sodium may be used with bile acid resins. When administering a bile-acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, Pravastatin Sodium should be given either 1 hour or more before or at least 4 hours following the resin. [See Clinical Pharmacology (12.3) ] 2.6 Dosage in Patients Taking Cyclosporine In patients taking immunosuppressive drugs such as cyclosporine concomitantly with pravastatin, therapy should begin with 10 mg of pravastatin sodium once-a-day at bedtime and titration to higher doses should be done with caution. Most patients treated with this combination received a maximum pravastatin sodium dose of 20 mg/day. In patients taking cyclosporine, therapy should be limited to 20 mg of pravastatin sodium once daily [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ]. 2.7 Dosage in Patients Taking Clarithromycin In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily [see Drug Interactions (7.2) ].

2.1 General Dosing Information 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 Sodium [see NCEP Treatment Guidelines for details on dietary therapy].

2.2 Adult Patients The recommended starting dose is 40 mg once daily. If a daily dose of 40 mg does not achieve desired cholesterol levels, 80 mg once daily is recommended. Pravastatin Sodium 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.

2.3 Patients with Renal Impairment In patients with severe renal impairment, a starting dose of 10 mg pravastatin daily is recommended.

2.4 Pedi …

3 DOSAGE FORMS AND STRENGTHS Pravastatin sodium tablets, USP are supplied as: 10 mg of pravastatin sodium: yellow, rectangular shaped with rounded edges, biconvex, uncoated tablets debossed with ‘Y’ on one side and ‘37’ on the other side. 20 mg of pravastatin sodium: white to off-white, rectangular shaped with rounded edges, biconvex, uncoated tablets debossed with ‘T’ on one side and ‘36’ on the other side. 40 mg of pravastatin sodium: yellow, rectangular shaped with rounded edges, biconvex, uncoated tablets debossed with ‘Y’ on one side and ‘39’ on the other side. 80 mg of pravastatin sodium: yellow, oval shaped biconvex, uncoated tablets, debossed with ‘Y’ on one side and ‘38’ on the other side. Tablets: 10 mg, 20 mg, 40 mg, and 80 mg of pravastatin sodium. ( 3 )

4 CONTRAINDICATIONS Hypersensitivity to any component of this medication. (4.1, 6.2, 11) Active liver disease or unexplained, persistent elevations of serum transaminases. (4.2, 5.3 ) Pregnancy (4.3, 8.1, 8.3) Lactation (4.4, 8.2) 4.1 Hypersensitivity Hypersensitivity to any component of this medication. 4.2 Liver Active liver disease or unexplained, persistent elevations of serum transaminases [see Warnings and Precautions (5.3) ]. 4.3 Pregnancy Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they are contraindicated during pregnancy and in nursing mothers. PRAVASTATIN SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this class of drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1, 8.3) ]. 4.4 Lactation Pravastatin is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require Pravastatin Sodium treatment should not breastfeed their infants [see Use in Specific Populations (8.2) ].

4.1 Hypersensitivity Hypersensitivity to any component of this medication.

4.2 Liver Active liver disease or unexplained, persistent elevations of serum transaminases [see Warnings and Precautions (5.3) ].

4.3 Pregnancy Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they are contraindicated during pregnancy and in nursing mothers. PRAVASTATIN SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this class of drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1, 8.3) ].

4.4 Lactation Pravastatin is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require Pravastatin Sodium treatment should not breastfeed their infants [see Use in Specific Populations (8.2) ].

6 ADVERSE REACTIONS 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. In short-term clinical trials, the most commonly reported adverse reactions (≥2% and > placebo) regardless of causality were: musculoskeletal pain, nausea/vomiting, upper respiratory infection, diarrhea, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Adverse Clinical Events Short-Term Controlled Trials In the pravastatin sodium tablets placebo-controlled clinical trials database of 1313 patients (age range 20 to 76 years, 32.4% women, 93.5% Caucasians, 5% Blacks, 0.9% Hispanics, 0.4% Asians, 0.2% Others) with a median treatment duration of 14 weeks, 3.3% of patients on pravastatin sodium tablets and 1.2% patients on placebo discontinued due to adverse events regardless of causality. The most common adverse reactions that led to treatment discontinuation and occurred at an incidence greater than placebo were: liver function test increased, nausea, anxiety/depression, and dizziness. All adverse clinical events (regardless of causality) reported in ≥2% of pravastatin-treated patients in placebo-controlled trials of up to 8 months duration are identified in Table 1: Table 1: Adverse Events in ≥2% of Patients Treated with Pravastatin 5 to 40 mg and at an Incidence Greater Than Placebo in Short-Term Placebo-Controlled Trials (% of patients) Body System/Event 5 mg N=100 10 mg N=153 20 mg N=478 40 mg N=171 Any Dose N=902 Placebo N=411 Cardiovascular Angina Pectoris 5.0 4.6 4.8 3.5 4.5 3.4 Dermatologic Rash 3.0 2.6 6.7 1.2 4.5 1.4 Gastrointestinal Nausea/Vomiting Diarrhea Flatulence Dyspepsia/Heartburn Abdominal Distension 4.0 8.0 2.0 0.0 2.0 5.9 8.5 3.3 3.3 3.3 10.5 6.5 4.6 3.6 2.1 2.3 4.7 0.0 0.6 0.6 7.4 6.7 3.2 2.5 2.0 7.1 5.6 4.4 2.7 2.4 General Fatigue Chest Pain Influenza 4.0 4.0 4.0 1.3 1.3 2.6 5.2 3.3 1.9 0.0 1.2 0.6 3.4 2.7 2.0 3.9 1.9 0.7 Musculoskeletal Musculoskeletal Pain Myalgia 13.0 1.0 3.9 2.6 13.2 2.9 5.3 1.2 10.1 2.3 10.2 1.2 Nervous System Headache Dizziness 5.0 4.0 6.5 1.3 7.5 5.2 3.5 0.6 6.3 3.5 4.6 3.4 Respiratory Pharyngitis Upper Respiratory Infection Rhinitis Cough 2.0 6.0 7.0 4.0 4.6 9.8 5.2 1.3 1.5 5.2 3.8 3.1 1.2 4.1 1.2 1.2 2.0 5.9 3.9 2.5 2.7 5.8 4.9 1.7 Investigation ALT Increased g-GT Increased CPK Increased 2.0 3.0 5.0 2.0 2.6 1.3 4.0 2.1 5.2 1.2 0.6 2.9 2.9 2.0 4.1 1.2 1.2 3.6 The safety and tolerability of pravastatin sodium tablets at a dose of 80 mg in 2 controlled trials with a mean exposure of 8.6 months was similar to that of pravastatin sodium tablets at lower doses except that 4 out of 464 patients taking 80 mg of pravastatin had a single elevation of CK >10 times ULN compared to 0 out of 115 patients taking 40 mg of pravastatin. Long-Term Controlled Morbidity and Mortality Trials In the pravastatin sodium tablets placebo-controlled clinical trials database of 21,483 patients (age range 24 to 75 years, 10.3% women, 52.3% Caucasians, 0.8% Blacks, 0.5% Hispanics, 0.1% Asians, 0.1% Others, 46.1% Not Recorded) with a median treatment duration of 261 weeks, 8.1% of patients on pravastatin sodium tablets and 9.3% patients on placebo discontinued due to adverse events regardless of causality. Adverse event data were pooled from 7 double-blind, placebo-controlled trials (West of Scotland Coronary Prevention Study [WOS]; Cholesterol and Recurrent Events study [CARE]; Long-term Intervention with Pravastatin in Ischemic Disease study [LIPID]; Pravastatin Limitation of Atherosclerosis in the Coronary Arteries study [PLAC I]; Pravastatin, Lipids and Atherosclerosis in the Carotids study [PLAC II]; Regression Growth Eva …

7 DRUG INTERACTIONS • See full prescribing information for details regarding concomitant use of pravastatin sodium with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 2.5 , 7.1 ) • Bile Acid Sequestrants: in patients taking a bile acid sequestrant, administer pravastatin sodium at least 1 hour before or at least 4 hours after the bile acid sequestrant ( 7.2 ) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pravastatin Sodium Pravastatin sodium is a substrate of the transport protein OATP1B1. Pravastatin sodium plasma levels can be significantly increased with concomitant administration of inhibitors of OATP1B1. Table 3 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with pravastatin sodium and instructions for preventing or managing them [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )]. Table 3: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pravastatin Sodium Gemfibrozil Clinical Impact: There is an increased risk of myopathy/rhabdomyolysis when pravastatin Sodium is administered with gemfibrozil Intervention: Avoid concomitant use of gemfibrozil with pravastatin sodium. Cyclosporine Clinical Impact: The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine with pravastatin sodium. Intervention: Initiate with a dosage of pravastatin sodium 10 mg once daily. Do not exceed pravastatin sodium 20 mg once daily [see Dosage and Administration ( Error! Hyperlink reference not valid. )]. Select Macrolide Antibiotics Clinical Impact: The risk of myopathy and rhabdomyolysis is increased by concomitant use of clarithromycin or erythromycin with pravastatin sodium. Other macrolides (e.g., azithromycin) have the potential to increase pravastatin sodium exposures and increase the risk of myopathy and rhabdomyolysis when used concomintantly. Intervention: For patients taking erythromycin or clarithromycin, do not exceed 40 mg pravastatin sodium once daily [see Dosage and Administration ( Error! Hyperlink reference not valid. )]. Niacin Clinical Impact: Cases of myopathy and rhabdomyolysis have been observed with concomitant use of niacin with pravastatin sodium. Intervention: Consider if the benefit of using niacin concomitantly with pravastatin sodium outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug. Fibrates (other than Gemfibrozil) Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with pravastatin sodium. Intervention: Consider if the benefit of using fibrates concomitantly with pravastatin sodium outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug. Colchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with pravastatin sodium. Intervention: Consider if the benefit of using colchicine concomitantly with pravastatin sodium outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug. 7.2 Drug Interactions that Decrease the Efficacy of Pravastatin Sodium Table 4 presents drug interactions that may decrease the efficacy of pravastatin sodium and instructions for preventing or managing them. Table 4: Drug Interactions that Decrease the Efficacy of Pravastatin Sodium Bile Acid Sequestrants Clinical Impact: Concomitant cholestyramine or colestipol administra …

8 USE IN SPECIFIC POPULATIONS • Pregnancy: May cause fetal harm () • Lactation: Breastfeeding not recommended during treatment with pravastatin sodium () 8.1 Pregnancy Risk Summary Discontinue pravastatin sodium when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. pravastatin sodium decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pravastatin sodium may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology ()]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. 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 hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with pravastatin sodium use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data). In animal reproduction studies, no evidence of fetal malformations was seen in pregnant rats or rabbits orally administered pravastatin during the period of organogenesis at doses that resulted in 10 times and 120 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 80 mg/day, based on body surface area (mg/m 2 ). An imbalance in some fetal skeletal variations, increased offspring mortality, and developmental delays occurred when pregnant rats were exposed to 10 times to 12 times the MRHD during organogenesis to parturition (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data A Medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential cofounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for cofounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Embryofetal and neonatal mortality was observed in rats given pravastatin during the period of organogenesis or during organogenesis continuing through weaning. In pregnant rats given oral gavage doses of 4, 20, 100, 500, and 1000 mg/kg/day from gestation days 7 through 17 (organogenesis) increased mortality of offspring and increased cervical rib skeletal anomalies were observed at ≥100 mg/kg/day systemic exposure, 10 times the human exposure at 80 mg/day MRHD based on body surface area (mg/m 2 ). In other studies …

12.1 Mechanism of Action Pravastatin is a reversible inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

12.2 Pharmacodynamics Inhibition of HMG-CoA reductase by pravastatin accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins. The maximum LDL-C reduction of pravastatin sodium is usually achieved by 4 weeks and is maintained after that.

11 DESCRIPTION Pravastatin sodium, USP is one of a class of lipid-lowering compounds, the statins, which reduce cholesterol biosynthesis. These agents are competitive inhibitors of HMG-CoA reductase, the enzyme catalyzing the early rate-limiting step in cholesterol biosynthesis, conversion of HMG-CoA to mevalonate. Pravastatin sodium, USP 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, [1 S -[1α (β S *,δ S *),2α,6α,8β( R *),8aα]]-. It has the following structural formula: C 23 H 35 NaO 7 M.W. 446.52 Pravastatin sodium, USP 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 USP are available for oral administration as 10 mg, 20 mg, 40 mg, and 80 mg tablets. Inactive ingredients include: calcium phosphate dibasic, crospovidone, lactose anhydrous, microcrystalline cellulose, and povidone. Additionally, the 10 mg, 20 mg, and 40 mg tablet contains croscarmellose sodium and sodium stearyl fumarate. Additionally, the 10 mg tablet contains ferric oxide red; the 20 mg tablet contains ferric oxide yellow; the 40 mg tablet contains FD&C Blue No. 1 Aluminum Lake and Yellow D&C No. 10; and the 80 mg tablet contains magnesium stearate. pravastatin sodium structural formula

OVERDOSAGE 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 .)

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Pravastatin sodium tablets, USP are supplied as: 10 mg tablets: Pink coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘1’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-008-15 Bottle of 90 tablets with a child-resistant closure 16729-008-16 Bottle of 500 tablets 16729-008-17 Bottle of 1000 tablets 20 mg tablets: Yellow coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘2’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-009-15 Bottle of 90 tablets with a child-resistant closure 16729-009-16 Bottle of 500 tablets 16729-009-17 Bottle of 1000 tablets 40 mg tablets: Light Green coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘8’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-010-15 Bottle of 90 tablets with a child-resistant closure 16729-010-16 Bottle of 500 tablets 16729-010-17 Bottle of 1000 tablets 80 mg tablets: Yellow coloured, mottled, oval shaped, uncoated tablets, debossed ‘PB’ on one side and ‘4’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-011-15 Bottle of 90 tablets with a child-resistant closure 16729-011-16 Bottle of 500 tablets 16729-011-17 Bottle of 1000 tablets Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.

16.1 How Supplied Pravastatin sodium tablets, USP are supplied as: 10 mg tablets: Pink coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘1’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-008-15 Bottle of 90 tablets with a child-resistant closure 16729-008-16 Bottle of 500 tablets 16729-008-17 Bottle of 1000 tablets 20 mg tablets: Yellow coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘2’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-009-15 Bottle of 90 tablets with a child-resistant closure 16729-009-16 Bottle of 500 tablets 16729-009-17 Bottle of 1000 tablets 40 mg tablets: Light Green coloured, mottled, rounded rectangular shaped, biconvex, uncoated tablets, debossed ‘PB’ on one side and ‘8’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-010-15 Bottle of 90 tablets with a child-resistant closure 16729-010-16 Bottle of 500 tablets 16729-010-17 Bottle of 1000 tablets 80 mg tablets: Yellow coloured, mottled, oval shaped, uncoated tablets, debossed ‘PB’ on one side and ‘4’ on other side. They are supplied in bottles containing desiccant canister as follows. NDC Number Size 16729-011-15 Bottle of 90 tablets with a child-resistant closure 16729-011-16 Bottle of 500 tablets 16729-011-17 Bottle of 1000 tablets Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.