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These highlights do not include all the information needed to use pravastatin sodium safely and effectively. See full prescribing information for pravastatin sodium tablets. Initial U.S. Approval: 1991 | pravastatin sodium

05:56 EDT 27th August 2014 | BioPortfolio
Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

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.

In hypercholesterolemic patients without clinically evident coronary heart disease (CHD), pravastatin sodium tablets are indicated to:

Pravastatin sodium tablets are indicated:

a.            LDL-C remains ≥ 190 mg/dL or

b.            LDL-C remains ≥ 160 mg/dL and:

Pravastatin sodium has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

The patient should be placed on a standard cholesterol-lowering diet before receiving pravastatin sodium tablets and should continue on this diet during treatment with pravastatin sodium tablets [see NCEP Treatment Guidelines for details on dietary therapy].

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. In patients with significant renal impairment, a starting dose of 10 mg daily is recommended. Pravastatin sodium tablets 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.

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)].

Pravastatin sodium tablets may be used with bile acid resins. When administering a bile-acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, pravastatin sodium tablets should be given either 1 hour or more before or at least 4 hours following the resin. [See Clinical Pharmacology (12.3).]

The combination of statins and fibrates should generally be used with caution. [See Warnings and Precautions (5.1).]

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)].

In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily [see Drug Interactions (7.2)].

Pravastatin sodium tablets, USP are supplied as:

10 mg tablets: white to off-white, oval-shaped, biconvex uncoated tablets debossed with the logo of ‘ZC46’ on one side and plain on the other side.

20 mg tablets: white to off-white, oval-shaped, biconvex uncoated tablets debossed with the logo of ‘ZC45’ on one side and plain on the other side.

40 mg tablets: white to off-white, oval-shaped, biconvex uncoated tablets debossed with the logo of ‘ZC44’ on one side and plain on the other side.

Hypersensitivity to any component of this medication.

Active liver disease or unexplained, persistent elevations of serum transaminases [see Warnings and Precautions (5.2)].

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)].

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with pravastatin and other drugs in this class. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects.

Uncomplicated myalgia has also been reported in pravastatin-treated patients [see Adverse Reactions (6)]. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), was rare (< 0.1%) in pravastatin clinical trials. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Predisposing factors include advanced age (> 65), uncontrolled hypothyroidism, and renal impairment. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Pravastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Pravastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.

The risk of myopathy during treatment with statins is increased with concurrent therapy with either erythromycin, cyclosporine, niacin, or fibrates. However, neither myopathy nor significant increases in CPK levels have been observed in   3 reports involving a total of 100 post-transplant patients (24 renal and 76 cardiac) treated for up to 2 years concurrently with pravastatin 10 to 40 mg and cyclosporine. Some of these patients also received other concomitant immunosuppressive therapies. Further, in clinical trials involving small numbers of patients who were treated concurrently with pravastatin and niacin, there were no reports of myopathy. Also, myopathy was not reported in a trial of combination pravastatin (40 mg/day) and gemfibrozil (1200 mg/day), although    4 of 75 patients on the combination showed marked CPK elevations versus 1 of 73 patients receiving placebo. There was a trend toward more frequent CPK elevations and patient withdrawals due to musculoskeletal symptoms in the group receiving combined treatment as compared with the groups receiving placebo, gemfibrozil, or pravastatin monotherapy. The use of fibrates alone may occasionally be associated with myopathy. The benefit of further alterations in lipid levels by the combined use of pravastatin sodium with fibrates should be carefully weighed against the potential risks of this combination.

Statins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. In 3 long-term (4.8 to 5.9 years), placebo-controlled clinical trials (WOS, LIPID, CARE), 19,592 subjects (19,768 randomized) were exposed to pravastatin or placebo [see Clinical Studies (14)]. In an analysis of serum transaminase values (ALT, AST), incidences of marked abnormalities were compared between the pravastatin and placebo treatment groups; a marked abnormality was defined as a post-treatment test value greater than 3 times the upper limit of normal for subjects with pretreatment values less than or equal to the upper limit of normal, or 4 times the pretreatment value for subjects with pretreatment values greater than the upper limit of normal but less than 1.5 times the upper limit of normal. Marked abnormalities of ALT or AST occurred with similar low frequency (≤ 1.2%) in both treatment groups. Overall, clinical trial experience showed that liver function test abnormalities observed during pravastatin therapy were usually asymptomatic, not associated with cholestasis, and did not appear to be related to treatment duration. In a 320-patient placebo-controlled clinical trial, subjects with chronic (> 6 months) stable liver disease, due primarily to hepatitis C or non-alcoholic fatty liver disease, were treated with 80 mg pravastatin or placebo for up to 9 months. The primary safety endpoint was the proportion of subjects with at least one ALT ≥ 2 times the upper limit of normal for those with normal ALT (≤ the upper limit of normal) at baseline or a doubling of the baseline ALT for those with elevated ALT (> the upper limit of normal) at baseline. By Week 36, 12 out of 160 (7.5%) subjects treated with pravastatin met the prespecified safety ALT endpoint compared to  20 out of 160 (12.5%) subjects receiving placebo. Conclusions regarding liver safety are limited since the study was not large enough to establish similarity between groups (with 95% confidence) in the rates of ALT elevation.

It is recommended that liver function tests be performed prior to the initiation of therapy and when clinically indicated.

Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of pravastatin [see Contraindications (4.2)]. Caution should be exercised when pravastatin is administered to patients who have a recent (< 6 months) history of liver disease, have signs that may suggest liver disease (e.g., unexplained aminotransferase elevations, jaundice), or are heavy users of alcohol.

Patients who develop increased transaminase levels or signs and symptoms of active liver disease while taking pravastatin should be evaluated with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) returns to normal. Should an increase in AST or ALT of 3 times the upper limit of normal or greater persist, withdrawal of pravastatin therapy is recommended.

Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Results of clinical trials with pravastatin in males and post-menopausal females were inconsistent with regard to possible effects of the drug on basal steroid hormone levels. In a study of 21 males, the mean testosterone response to human chorionic gonadotropin was significantly reduced (p < 0.004) after 16 weeks of treatment with 40 mg of pravastatin. However, the percentage of patients showing a ≥ 50% rise in plasma testosterone after human chorionic gonadotropin stimulation did not change significantly after therapy in these patients. The effects of statins on spermatogenesis and fertility have not been studied in adequate numbers of patients. The effects, if any, of pravastatin on the pituitary-gonadal axis in pre-menopausal females are unknown. Patients treated with pravastatin who display clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should also be exercised if a statin or other agent used to lower cholesterol levels is administered to patients also receiving other drugs (e.g., ketoconazole, spironolactone, cimetidine) that may diminish the levels or activity of steroid hormones.

In a placebo-controlled study of 214 pediatric patients with HeFH, of which 106 were treated with pravastatin (20 mg in the children aged 8 to 13 years and 40 mg in the adolescents aged 14 to 18 years) for 2 years, there were no detectable differences seen in any of the endocrine parameters (ACTH, cortisol, DHEAS, FSH, LH, TSH, estradiol [girls] or testosterone [boys]) relative to placebo. There were no detectable differences seen in height and weight changes, testicular volume changes, or Tanner score relative to placebo.

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.

Short-Term Controlled Trials

In the pravastatin sodium 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 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:

The safety and tolerability of pravastatin sodium 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 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 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 and 9.3% patients on placebo discontinued due to adverse events regardless of causality.

Adverse event data were pooled from 7 doubleblind, 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 Evaluation Statin Study [REGRESS]; and Kuopio Atherosclerosis Prevention Study [KAPS]) involving a total of 10,764 patients treated with pravastatin 40 mg and 10,719 patients treated with placebo. The safety and tolerability profile in the pravastatin group was comparable to that of the placebo group. Patients were exposed to pravastatin for a mean of 4 to 5.1 years in WOS, CARE, and LIPID and 1.9 to 2.9 years in PLAC I, PLAC II, KAPS, and REGRESS. In these long-term trials, the most common reasons for discontinuation were mild, non-specific gastrointestinal complaints. Collectively, these 7 trials represent 47,613 patient-years of exposure to pravastatin. All clinical adverse events (regardless of causality) occurring in ≥ 2% of patients treated with pravastatin in these studies are identified in Table 2.

In addition to the events listed above in the long-term trials table, events of probable, possible, or uncertain relationship to study drug that occurred in < 2 % of pravastatin-treated patients in the long-term trials included the following:

Dermatologic

scalp hair abnormality (including alopecia), urticaria.

Endocrine/Metabolic

sexual dysfunction, libido change.

General

flushing.

Immunologic

allergy, edema head/neck.

Musculoskeletal

muscle weakness.

Nervous System

vertigo, insomnia, memory impairment, neuropathy (including peripheral neuropathy).

Special Senses

taste disturbance.

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
4.6
4.8
3.5
4.5
3.4
Dermatologic
Rash 
3
2.6
6.7
1.2
4.5
1.4
Gastrointestinal
Nausea/Vomiting
Diarrhea
Flatulence
Dyspepsia/Heartburn
Abdominal Distension 
4
8
2
0
2
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
0.6
0.6
7.4
6.7
3.2
2.5
2
7.1
5.6
4.4
2.7
2.4
General






Fatigue 
4
1.3
5.2
0
3.4
3.9
Chest Pain
Influenza 
4
4
1.3
2.6
3.3
1.9
1.2
0.6
2.7
2
1.9
0.7
Musculoskeletal






Musculoskeletal Pain 
13
3.9
13.2
5.3
10.1
10.2
Myalgia 
1
2.6
2.9
1.2
2.3
1.2
Nervous System
Headache
Dizziness 
5
4
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
6
7
4
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
5.9
3.9
2.5
2.7
5.8
4.9
1.7
Investigation
ALT Increased
g-GT Increased
CPK Increased 
2
3
5
2
2.6
1.3
4
2.1
5.2
1.2
0.6
2.9
2.9
2
4.1
1.2
1.2
3.6
Table 2. Adverse Events in ≥ 2% of Patients Treated with Pravastatin 40 mg and at an Incidence Greater Than Placebo in Long-Term Placebo-Controlled Trials
Body  System / Event 
Pravastatin  ( N = 10 , 764 ) 
%  of  patients
Placebo  ( N = 10 , 719 ) 
%  of  patients
Dermatologic
Rash (including dermatitis) 
7.2
7.1
General


Edema
3
2.7
Fatigue
8.4
7.8
Chest Pain 
10
9.8
Fever
2.1
1.9
Weight Gain
3.8
3.3
Weight Loss 
3.3
2.8
Musculoskeletal


Musculoskeletal Pain 
24.9
24.4
Muscle Cramp
5.1
4.6
Musculoskeletal Traumatism 
10.2
9.6
Nervous System


Dizziness 
7.3
6.6
Sleep Disturbance 
3
2.4
Anxiety/Nervousness
4.8
4.7
Paresthesia 
3.2
3
Renal/Genitourinary
Urinary Tract Infection
2.7
2.6
Respiratory


Upper Respiratory Tract Infection 
21.2
20.2
Cough 
8.2
7.4
Influenza 
9.2
9
Pulmonary Infection
3.8
3.5
Sinus Abnormality
Tracheobronchitis 
7
3.4
6.7
3.1
Special Senses
Vision Disturbance (includes blurred vision, diplopia) 
3.4
3.3
Infections
Viral Infection 
3.2
2.9

In addition to the events reported above, as with other drugs in this class, the following events have been reported rarely during postmarketing experience with pravastatin sodium, regardless of causality assessment:

Musculoskeletal

myopathy, rhabdomyolysis.

Nervous System

dysfunction of certain cranial nerves (including alteration of taste, impairment of extraocular movement, facial paresis), peripheral nerve palsy.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Hypersensitivity

anaphylaxis, angioedema, lupus erythematosus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, hemolytic anemia, positive ANA, ESR increase, arthritis, arthralgia, asthenia, photosensitivity, chills, malaise, toxic epidermal necrolysis, erythema multiforme (including Stevens-Johnson syndrome).

Gastrointestinal

abdominal pain, constipation, pancreatitis, hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma.

Dermatologic

a variety of skin changes (e.g., nodules, discoloration, dryness of mucous membranes, changes to hair/nails).

Renal

urinary abnormality (including dysuria, frequency, nocturia).

Respiratory

dyspnea.

Reproductive

gynecomastia.

Laboratory Abnormalities

liver function test abnormalities, thyroid function abnormalities.

Increases in ALT, AST values and CPK have been observed [see Warnings and Precautions (5.1, 5.2)].

Transient, asymptomatic eosinophilia has been reported. Eosinophil counts usually returned to normal despite continued therapy. Anemia, thrombocytopenia, and leukopenia have been reported with statins.

In a 2 year, doubleblind, placebo-controlled study involving 100 boys and 114 girls with HeFH (n=214; age range 8 to 18.5 years, 53% female, 95% Caucasians, < 1% Blacks, 3% Asians, 1% Other), the safety and tolerability profile of pravastatin was generally similar to that of placebo. [See Warnings and Precautions (5.3), Use in Specific Populations (8.4), and Clinical Pharmacology (12.3).]

For the concurrent therapy of either cyclosporine, fibrates, niacin (nicotinic acid), or erythromycin, the risk of myopathy increases [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

The risk of myopathy/rhabdomyolysis is increased with concomitant administration of cyclosporine. Limit pravastatin to 20 mg once daily for concomitant use with cyclosporine [see Dosage and Administration (2.5), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

The risk of myopathy/rhabdomyolysis is increased with concomitant administration of clarithromycin. Limit pravastatin to 40 mg once daily for concomitant use with clarithromycin [see Dosage and Administration (2.6), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

Pregnancy Category X

[See Contraindications (4.3).]

Safety in pregnant women has not been established. Available data in women inadvertently taking pravastatin while pregnant do not suggest any adverse clinical events. However, there are no adequate and well-controlled studies in pregnant women. Therefore, it is not known whether pravastatin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Pravastatin should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus and patients have been informed of the potential hazards.

Rare reports of congenital anomalies have been received following intrauterine exposure to other statins. In a reviewof approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a ≥ 3- to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. As safety in pregnant women has not been established and there is no apparent benefit to therapy with pravastatin sodium during pregnancy [see Contraindications (4.3)], treatment should be immediately discontinued as soon as pregnancy is recognized. Pravastatin sodium should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards.

Pravastatin was neither embryolethal nor teratogenic in rats at doses up to 1000 mg/kg daily or in rabbits at doses of up to 50 mg/kg daily. These doses resulted in 10 times (rabbit) or 120 times (rat) the human exposure at 80 mg/day maximum recommended human dose (MRHD) based on surface area (mg/m).

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 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).

In pregnant rats given oral gavage doses of 10, 100, and 1000 mg/kg/day from gestation day 17 through lactation day 21 (weaning) increased mortality of offspring and developmental delays were observed at 100 mg/kg/day systemic exposure, 12 times the human exposure at 80 mg/day MRHD based on body surface area (mg/m).

A small amount of pravastatin is excreted in human breastmilk. 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 (4.4)].

Pravastatin crosses the placenta and is found in fetal tissue at 30% maternal plasma levels following a single 20 mg/kg dose given to pregnant rats on gestation day 18. Similar studies in lactating rats indicate secretion of pravastatin into breastmilk at 0.2 to 6.5 times higher levels than maternal plasma at exposures equivalent to 2 times human exposure at the MRHD.

The safety and effectiveness of pravastatin sodium in children and adolescents from 8 to 18 years of age have been evaluated in a placebo-controlled study of     2 years duration. Patients treated with pravastatin had an adverse experience profile generally similar to that of patients treated with placebo with influenza and headache commonly reported in both treatment groups. [See Adverse Reactions (6.4).] Doses greater than 40 mg have not been studied in this population. Children and adolescent females of childbearing potential should be counseled on appropriate contraceptive methods while on pravastatin therapy [see Contraindications (4.3) and Use in Specific Populations (8.1)]. For dosing information [see Dosage and Administration (2.3).]

Doubleblind, placebo-controlled pravastatin studies in children less than 8 years of age have not been conducted.

The beneficial effect of pravastatin in elderly subjects in reducing cardiovascular events and in modifying lipid profiles was similar to that seen in younger subjects. The adverse event profile in the elderly was similar to that in the overall population. Other reported clinical experience has not identified differences in responses to pravastatin between elderly and younger patients.

Mean pravastatin AUCs are slightly (25% to 50%) higher in elderly subjects than in healthy young subjects, but mean maximum plasma concentration (C), time to maximum plasma concentration (T), and half-life (t) values are similar in both age groups and substantial accumulation of pravastatin would not be expected in the elderly [see Clinical Pharmacology (12.3)].

Since advanced age (≥ 65 years) is a predisposing factor for myopathy, pravastatin sodium should be prescribed with caution in the elderly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Pravastatin has not been evaluated in patients with rare homozygous familial hypercholesterolemia. In this group of patients, it has been reported that statins are less effective because the patients lack functional LDL receptors.

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.

Pravastatin sodium 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 is designated chemically as 1-Naphthalene-heptanoic 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))-.

Structural formula:

CHNaO     MW 446.52

Pravastatin sodium is white to yellowish white powder or crystalline powder, hygroscopic in nature. It is a relatively polar hydrophilic compound with a partition coefficient (octanol/water) of 0.59 at a pH of 7. It is freely soluble in water and in methanol. Soluble in ethanol.

Each pravastatin sodium tablet intended for oral administration contains 10 mg or 20 mg or 40 mg or 80 mg of pravastatin sodium. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose anhydrous, magnesium stearate, microcrystalline cellulose, polyoxyl 35 castor oil and sodium carbonate anhydrous.

Pravastatin is a reversible inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, pravastatin reduces VLDL and TG and increases HDL-C.

General

Absorption

Pravastatin sodium is administered orally in the active form. In studies in man, peak plasma pravastatin concentrations occurred 1 to 1.5 hours upon oral administration. Based on urinary recovery of total radiolabeled drug, the average oral absorption of pravastatin is 34% and absolute bioavailability is 17%. While the presence of food in the gastrointestinal tract reduces systemic bioavailability, the lipi

Manufacturer

American Health Packaging

Active Ingredients

Source

Drugs and Medications [36 Associated Drugs and Medications listed on BioPortfolio]

Pravachol [E.R. Squibb & Sons, L.L.C.]

These highlights do not include all the information needed to use PRAVACHOL safely and effectively. See full prescribing information for PRAVACHOL. PRAVACHOL (pravastatin sodium) Tablets Initial U.S. ...

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Clinical Trials [1312 Associated Clinical Trials listed on BioPortfolio]

Fed, Bioequivalence Study of Pravastatin Sodium 80 mg Tablets Versus Pravachol® 80 mg Tablets In Subjects

This study was designed to compare the rate and extent of absorption of pravastatin sodium from the following formulations under fed conditions: 1. Pravastatin Sodium 80 mg Tablets (Gen...

Fasting Bioequivalence Study of Pravastatin Sodium 80 mg Tablets Versus Pravachol® 80 mg Tablets In Normal Healthy Subjects

The objective of this study was to compare the rate and extent of absorption of pravastatin sodium from a test formulation of Pravastatin Sodium 80 mg Tablets versus the reference Pravacho...

Pravastatin Sodium 80 mg Tablets Under Fasting Conditions

The objective of this study is to evaluate the comparative bioavailability between pravastatin sodium 80 mg tablets (Distributed by Teva Pharmaceuticals, USA) and Pravachol® 80 mg tablets...

Bioequivalence Study of Pravastatin Sodium Tablets 80 mg Under Fasting Conditions

This is a single Dose Two-Way Crossover Fasting Bioequivalence Study of Pravastatin 80 mg Tablets of Dr.Reddy's Laboratories Limited with Pravachol 80 mg, Bristol Myers Squibb in Healthy V...

Pravastatin 80 mg Tablets Dosed in Healthy Subjects Under Non-Fasting Conditions

This study compared the relative bioavailability (rate and extent of absorption) of Pravastatin Sodium Tablets 80 mg by Teva Pharmaceutical Industries, Ltd. with that of Pravachol® Tablet...

PubMed Articles [1591 Associated PubMed Articles listed on BioPortfolio]

Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair.

Different genetic variants in the SLCO1B1 gene have been shown to have functional importance in individual variability in pravastatin pharmacokinetics, resulting in different inflammatory responses to...

Quantification of pravastatin acid, lactone and isomers in human plasma by UHPLC-MS/MS and its application to a pediatric pharmacokinetic study.

An ultra high pressure liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method for the simultaneous quantitation of pravastatin and major metabolites, 3'α-hydroxy-pravastatin, pravalacto...

Achieving the WHO sodium target: estimation of reductions required in the sodium content of packaged foods and other sources of dietary sodium.

Excess sodium intake is one of the top 2 dietary risk factors contributing to the global burden of disease. As such, many countries are now developing national sodium reduction strategies, a key compo...

Characterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats.

Quantitative assessment of potential drug-drug interactions (DDIs) is one of the major focuses in drug development. The aim of the present study was to quantitatively evaluate in vitro-in vivo discr...

Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.

Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes...

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