Lipid Metabolism Regulator
Action And Clinical Pharmacology: Pravastatin is one of a new class of lipid-lowering compounds known as HMG-CoA reductase inhibitors (statins) that 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 is isolated from a strain of Penicillium citrinum. The active drug substance is the hydroxyacid form.
Pravastatin produces its lipid-lowering effect in 2 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 low density lipoproteins (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 very low density lipoproteins (VLDL), the LDL precursor.
Epidemiologic and clinical studies have associated the risk of coronary artery disease (CAD) with elevated levels of Total-C, LDL-C and decreased levels of HDL-C. These abnormalities of lipoprotein metabolism are considered as major contributors to the development of the disease. Other factors, e.g., interactions between lipids/lipoproteins and endothelium, platelets and macrophages, have also been incriminated in the development of human atherosclerosis and of its complications.
In long-term, prospective clinical trials effective treatment of hypercholesterolemia/dyslipidemia has consistently been associated with a reduction in the risk of CAD.
Treatment with pravastatin has been shown to reduce circulating Total-C, LDL-C, and apolipoprotein B, modestly reduce VLDL-C and triglycerides (TG) while producing increases of variable magnitude in HDL-C and apolipoprotein A. Clinical trials suggest that pravastatin’s effect on reducing clinical events appears to incorporate both cholesterol modification and some ancillary mechanism.
Pravastatin has complex pharmacokinetic characteristics.
Pharmacokinetics: Pravastatin is administered orally in the active form. Following oral ingestion, pravastatin is rapidly absorbed with peak plasma levels attained at about 1 to 1.5 hours. Average oral absorption of pravastatin, based on urinary recovery of radiolabeled drug after oral and i.v. dosing, is 34%; average absolute bioavailability of the parent drug is 17%. The therapeutic response to pravastatin is similar, whether taken with meals or 1 hour prior to meals, even though the presence of food in the gastrointestinal tract causes a reduction in systemic bioavailability (see Table I).
Pravastatin undergoes extensive first pass extraction in the liver (estimated hepatic extraction ratio, 66%), its primary site of action, and is excreted in the bile. Therefore, plasma levels of the drug are probably of limited value in predicting therapeutic effectiveness. Nevertheless, measurement of plasma pravastatin concentrations by gas chromatography and mass-spectrometry showed dose proportionality for area under the concentration-time curve (AUC) and maximum and steady-state plasma levels. Steady-state areas under the plasma concentration-time curves and maximum (Cmax) or minimum (Cmin) plasma concentrations showed no accumulation following once or twice-daily administration of pravastatin tablets.
Protein binding of pravastatin is approximately 50%. The plasma elimination half-life of pravastatin is between 1.5 and 2 hours (2.5 to 3 hours in hypercholesterolemic subjects). Approximately 20% of a radiolabeled oral dose is excreted in the urine and 70% in the feces. Pravastatin is extensively metabolized. The major metabolite is the 3 a-hydroxy isomer, which has one-tenth to one-fortieth of the inhibitory activity of the parent compound on HMG-CoA reductase.
After i.v. administration to healthy subjects, approximately 47% of the total drug clearance occurs via renal excretion of intact pravastatin, and about 53% is cleared by nonrenal routes, i.e., biliary excretion and biotransformation.
Studies of pravastatin administered as a single dose to healthy elderly male and female subjects (age 65 to 78 years) indicated a 30 to 50% increase in plasma levels.
No studies have been carried out in patients with renal insufficiency.
Indications And Clinical Uses: Therapy with lipid-altering agents should be considered a component of multiple risk factor intervention in those individuals at increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Pravastatin should be used in addition to a diet restricted in saturated fat and cholesterol when the response to diet and other nonpharmacological measures alone has been inadequate.
Hypercholesterolemia: As an adjunct to diet [at least an equivalent of the American Heart Association (AHA) Step 1 diet] for the reduction of elevated total and low density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolemia (Types IIa and IIb), when the response to diet and other nonpharmacologic measures alone has been inadequate.
Prior to initiating therapy with pravastatin, secondary causes for hypercholesterolemia, such as obesity, poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy or alcoholism, should be excluded and it should be determined that patients for whom treatment with pravastatin is being considered have an elevated LDL-C level as the cause for an elevated total serum cholesterol. A lipid profile should be performed to measure total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG).
For patients with total triglycerides less than 4.52 mmol/L (400 mg/dL), LDL-C can be estimated using the following equation:
LDL-C (mmol/L) = Total Cholesterol – [(0.37 x triglycerides) + HDL-C] LDL-C (mg/dL) = Total Cholesterol – [(0.16 x triglycerides) + HDL-C]
When total triglyceride levels exceed 4.52 mmol/L (400 mg/dL), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation.
Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the Total-C be used to monitor therapy.
As with other lipid-lowering therapy, pravastatin is not indicated when hypercholesterolemia is due to hyperalphalipoproteinemia (elevated HDL-C). The efficacy of pravastatin has not been evaluated in conditions where the major abnormality is elevation of chylomicrons, VLDL or LDL (i.e., hyperlipoproteinemia or dyslipoproteinemia types I, III, IV or V).
Coronary Heart Disease: Pravastatin was also found to reduce the rate of progression of atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower Total and LDL-cholesterol to target levels. In 2 trials including this type of patients (i.e., in a secondary prevention intervention), pravastatin monotherapy was shown to reduce the rate of progression of atherosclerosis as evaluated by quantitative angiography and B-mode ultrasound. This effect may be associated with an improvement in the coronary endpoints (fatal or nonfatal myocardial infarction) (see Precautions).
In hypercholesterolemic patients without clinically evident coronary heart disease, pravastatin is indicated to: reduce the risk of myocardial infarction; reduce the risk for undergoing myocardial revascularization procedures; reduce the risk of cardiovascular mortality with no increase in death from noncardiovascular causes.
In the West of Scotland Study (WOS), the effect of pravastatin treatment on fatal and nonfatal coronary heart disease (CHD) was assessed in 6 595 patients (aged 45 to 66 years) without a previous myocardial infarction, but with elevated LDL-C levels between 4 to 6.7 mmol/L (156 to 254 mg/dL). The patients were followed for a median of 4.8 years.
Pravastatin significantly reduced the rate of first coronary events (either CHD death or nonfatal myocardial infarction) by 31% (248 events in the placebo group [CHD death = 44, nonfatal myocardial infarction = 204] vs 174 events in the pravastatin group [CHD death = 31, nonfatal myocardial infarction = 143], p = 0.0001). The effect of these cumulative cardiovascular event rates was evident after 6 months of treatment. The risk reduction with pravastatin was similar and significant throughout the entire range of baseline LDL cholesterol levels. This reduction was also similar and significant across the age range studied with a 40% risk reduction for patients younger than 55 years and a 27% risk reduction for patients 55 years and older.
Pravastatin also significantly decreased the risk for undergoing myocardial revascularization procedures (coronary artery bypass graft surgery by 37% [80 vs 51 patients, p = 0.009] and coronary angiography by 31% [128 vs 90, p = 0.007]). Cardiovascular deaths were decreased by 32% (73 vs 50, p = 0.03), and there was no increase in deaths from noncardiovascular causes.
The West of Scotland Study excluded female patients, elderly subjects and most patients with familial hypercholesterolemia (FH). Consequently it has not been established to what extent the findings of the WOS study can be extrapolated to these subpopulations of hypercholesterolemic patients.
In patients with heterozygous FH, optimal reduction in total and LDL cholesterol necessitates a combination drug therapy in the majority of patients. (For homozygous FH see Precautions, Use in Homozygous Familial Hypercholesterolemia.)
Because information on familial combined hyperlipidemic (FCH) patients is not available from the WOS study, the effect of pravastatin in this subgroup of high risk dyslipidemic patients could not be assessed.
Contra-Indications: Hypersensitivity to any component of this medication. Active liver disease or unexplained persistent elevations in liver function tests (see Warnings).
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 HMG-CoA reductase inhibitors such as pravastatin decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. Therefore, pravastatin is contraindicated during pregnancy.
Lactation: See Precautions.
Manufacturers’ Warnings In Clinical States: Liver Dysfunction: HMG-CoA reductase inhibitors have been associated with biochemical abnormalities of liver function. As with other lipid-lowering agents, including nonabsorbable bile acid-binding resins, increases in liver enzymes to less than 3 times the upper limit of normal have occurred during therapy with pravastatin. The significance of these changes, which usually appear during the first few months of treatment initiation, is not known. In the majority of patients treated with pravastatin, in clinical trials, these increased values declined to pretreatment levels despite continuation of therapy at the same dose.
Marked persistent increases (greater than 3 times the upper limit of normal) in serum transaminases were seen in 6 out of 1 142 (0.5%) patients treated with pravastatin in clinical trials (see Adverse Effects). The increases usually appeared 3 to 12 months after the start of therapy with pravastatin. These elevations were not associated with clinical signs and symptoms of liver disease and usually declined to pretreatment levels upon discontinuation of therapy. Patients rarely had persistent marked abnormalities possibly attributable to therapy.
Liver function tests should be performed at baseline and periodically thereafter in all patients. Special attention should be given to patients who develop increased transaminase levels. Liver function tests should be repeated to confirm an elevation and subsequently monitored at more frequent intervals. If increases in ALT and AST equal or exceed 3 times the upper limit of normal and persist, therapy should be discontinued.
Caution should be exercised when pravastatin is administered to patients with a history of liver disease or heavy alcohol ingestion. Active liver disease or unexplained serum transaminase elevations are contraindications to the use of pravastatin; if such condition develops during therapy, the drug should be discontinued.
Muscle Effects: Elevations of creatinine phosphokinase levels (CPK [MM fraction]), myalgia, myopathy and rhabdomyolysis have been reported with the use of HMG-CoA reductase inhibitors, including pravastatin.
Muscle weakness and rhabdomyolysis have been reported in patients receiving other HMG-CoA reductase inhibitors concomitantly with itraconazole and cyclosporine.
The benefits and risks of using HMG-CoA reductase inhibitors concomitantly with immunosuppressive drugs, fibrates, erythromycin, systemic azole derivative antifungal agents or lipid-lowering doses of niacin should be carefully considered.
Myalgia has been associated with pravastatin therapy. Rare cases of rhabdomyolysis associated with pravastatin (and macrocreatine kinase in 1 case) have been reported.
Myopathy (markedly elevated CPK of greater than 10 times the upper limit of normal with myalgia) was very rarely reported in pravastatin treated patients in clinical trials. Rhabdomyolysis with renal dysfunction secondary to myoglobinuria has also very rarely been reported with pravastatin. However, myopathy should be considered in any patients with diffuse myalgia, muscle tenderness or weakness, and/or marked elevation of CPK.
As with other statins, the risk of myopathy including rhabdomyolysis may be substantially increased by concomitant immunosuppressive therapy including cyclosporine, and by concomitant therapy with gemfibrozil, erythromycin or niacin (see Precautions).
Myopathy has not been observed in clinical trials involving small numbers of patients who were treated with pravastatin together with immunosuppressants, fibric acid derivatives or niacin.
The use of fibrates alone is occasionally associated with myopathy. In a limited size clinical trial of combined therapy with pravastatin (40 mg/day) and gemfibrozil (1 200 mg/day), myopathy was not reported, although a trend towards CPK elevations and musculoskeletal symptoms was seen. The combined use of pravastatin and fibrates should generally be avoided.
No information is available on the combined therapy of pravastatin with erythromycin.
Pravastatin therapy should be discontinued if marked elevation of CPK levels occurs or if myopathy is diagnosed or suspected.
Interruption of therapy with pravastatin should be considered in any patient with an acute, serious condition, suggestive of a myopathy or having a risk factor predisposing to the development of renal failure or rhabdomyolysis, such as severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disorders and uncontrolled seizures.
Precautions: General: In secondary prevention intervention, the effects of pravastatin-induced changes in lipoprotein levels, including reduction of total and LDL cholesterol, on total mortality have not been established.
Before instituting therapy with pravastatin an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in overweight and obese patients, and to treat other underlying medical problems (see Indications). The patient should be advised to inform subsequent physicians of the prior use of pravastatin.
Pravastatin may elevate creatine phosphokinase and transaminase levels. This should be considered in the differential diagnosis of chest pain in a patient on therapy with pravastatin.
Effect on the Lens: Current data from clinical trials do not indicate an adverse effect of pravastatin on the human lens.
Homozygous Familial Hypercholesterolemia: Pravastatin has not been evaluated in patients with rare homozygous familial hypercholesterolemia. Most HMG-CoA reductase inhibitors are less or not effective in this subgroup of hypercholesterolemic patients.
Effect on Lipoprotein(a): In some patients, the beneficial effect of lowered total cholesterol and LDL-C levels may be partly blunted by a concomitant increase in the lipoprotein (a)[Lp(a)] level. Further research is ongoing to elucidate the significance of Lp(a) variations. Therefore, until further experience is obtained, where feasible, it is suggested that measurements of serum Lp(a) be followed up in patients placed on pravastatin therapy.
Effect on CoQ10 Levels (Ubiquinone): A significant short-term decrease in plasma CoQ10 levels in patients treated with pravastatin has been observed. Longer clinical trials have also shown reduced serum ubiquinone levels during treatment with pravastatin and other HMG CoA reductase inhibitors. The clinical significance of a potential long-term statin-induced deficiency of CoQ10 has not yet been established. It has been reported that a decrease in myocardial ubiquinone levels could lead to impaired cardiac function in patients with borderline congestive heart failure.
Carcinogenesis: A 21-month oral study in mice, with doses of 10 to 100 mg/kg daily of pravastatin did not demonstrate any carcinogenic potential. In a 2-year oral study in rats, a statistically significant increase in the incidence of hepatocellular carcinoma was observed in male rats given 100 mg/kg daily (125 times the maximum human dose) of pravastatin. This change was not seen in male rats given 40 mg/kg daily (50 times the recommended human dose) or less, or in female rats at any dose level.
Pregnancy: Pravastatin is contraindicated during pregnancy (see Contraindications).
Safety in pregnant women has not been established. Although pravastatin was not teratogenic in rats at doses as high as 1 000 mg/kg daily nor in rabbits at doses of up to 50 mg/kg daily, pravastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of potential hazards. If a woman becomes pregnant while taking pravastatin, pravastatin should be discontinued and the patient advised again as to the potential hazards to the fetus.
Lactation: A negligible amount of pravastatin is excreted in human breast milk. Because of the potential for adverse reactions in nursing infants, if the mother is being treated with pravastatin, nursing should be discontinued or treatment with pravastatin stopped.
Children: Only limited experience with the use of statins in children is available. There is no experience to date with the use of pravastatin in such patients.
Geriatrics: Pharmacokinetic evaluation of pravastatin in patients over the age of 65 years indicates an increased AUC. There were no reported increases in the incidence of adverse effects in these or other studies involving patients in that age group. As a precautionary measure, the lowest dose should be administered initially.
Patients with Impaired Renal Function: There have been no studies on the use of pravastatin in patients with renal failure. As a precautionary measure, the lowest dose should be used in these patients (see Warnings, Muscle Effects).
Hypersensitivity: With lovastatin an apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus-like syndrome, polymyalgia rheumatica, thrombocytopenia, leukopenia, hemolytic anemia, positive antinuclear antibody (ANA), erythrocytes sedimentation rate (ESR) increase, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever and malaise.
Although to date hypersensitivity syndrome has not been described as such, in few instances eosinophilia and skin eruptions appear to be associated with pravastatin treatment. If hypersensitivity is suspected pravastatin should be discontinued. Patients should be advised to report promptly any signs of hypersensitivity such as angioedema, urticaria, photosensitivity, polyarthralgia, fever, malaise.
Endocrine Function: HMG-CoA reductase inhibitors interfere with cholesterol synthesis and as such could theoretically blunt adrenal and/or gonadal steroid production.
In one long-term study investigating the endocrine function in hypercholesterolemic patients, pravastatin exhibited no effect upon basal and stimulated cortisol levels, as well as on aldosterone secretion. Although no change was reported in the testicular function, conflicting results were observed in the analysis of sperm motility after administration of pravastatin. A case of reversible impotence has been reported in a 57-year old man administered pravastatin 20 mg/day and metoprolol. A causal relationship to therapy with pravastatin has not been established. Further studies are needed to clarify the effects of HMG CoA reductase inhibitors on male fertility. Furthermore, the effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown.
Patients treated with pravastatin who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should be exercised if an HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered to patients receiving other drugs (e.g., ketoconazole, spironolactone, or cimetidine) that may decrease the levels of endogenous steroid hormones.
Drug Interactions: Concomitant Therapy with Other Lipid Metabolism Regulators: Combined drug therapy should be approached with caution as information from controlled studies is limited.
Bile Acid Sequestrants: Preliminary evidence suggests that the cholesterol-lowering effects of pravastatin and the bile acid sequestrants, cholestyramine/colestipol are additive.
When pravastatin was administered 1 hour before or 4 hours after cholestyramine or 1 hour before colestipol and a standard meal, there was no clinically significant decrease in bioavailability or therapeutic effect. Concomitant administration resulted in an approximately 40 to 50% decrease in the mean AUC of pravastatin (see Dosage, Concomitant Therapy).
Gemfibrozil, Nicotinic Acid and Probucol: Gemfibrozil, nicotinic acid and probucol do not statistically significantly affect the bioavailability of pravastatin. However, in a limited size clinical trial, a trend toward CPK elevations and musculoskeletal symptoms was seen in patients treated concurrently with pravastatin and gemfibrozil. No results are available from clinical studies involving combination of pravastatin with probucol.
Myopathy, including rhabdomyolysis, has occurred in patients who were receving coadministration of HMG-CoA reductase inhibitors with fibric acid derivatives and niacin, particularly in subjects with pre-existing renal insufficiency (see Warnings, Muscle Effects).
Other Concomitant Therapy: Digoxin: Coadministration of digoxin and other HMG CoA reductase inhibitors has been shown to increase the steady state digoxin concentrations. The potential effects of coadministration of digoxin and pravastatin are not known. As a precautionary measure, patients taking digoxin should be closely monitored.
Antipyrine: Antipyrine was used as a model for drugs metabolized by the microsomal hepatic enzyme system (cytochrome P450 system). Pravastatin had no effect on the pharmacokinetics of antipyrine.
Coumarin Anticoagulants: Bioavailability parameters at steady state for pravastatin were not altered following concomitant administration with warfarin. Dosing of the 2 drugs did not produce any changes in the anticoagulant action of warfarin (i.e., no increase was seen in mean prothrombin time after 6 days of concomitant therapy). However, until further clinical experience is gained careful monitoring of prothrombin time is recommended in patients taking coumarin anticoagulants concomitantly with pravastatin.
Antacids and Cimetidine: On the average, antacids (1 hour prior to pravastatin) reduce and cimetidine increases the bioavailability of pravastatin. These changes were not statistically significant. The clinical significance of these interactions is not known but is probably minimal as judged from the interaction with food (see Pharmacology).
No information is available regarding interactions with erythromycin (see Warnings, Muscle Effects).
Although specific interaction studies were not performed during clinical trials, no noticeable drug interactions were reported when pravastatin was added to diuretics, antihypertensives, digitalis, angiotensin converting-enzyme (ACE) inhibitors, calcium channel blockers, or nitroglycerin.
Propranolol: Coadministration of propranolol and pravastatin reduced the AUC values by 23% and 16% respectively.
Cyclosporine: In a multicentre study, the AUC values of pravastatin were shown to be 5-fold higher in the presence of cyclosporine. There was no accumulation of pravastatin after multiple doses.
Adverse Reactions: Based on experience in a total of over 4 300 patients, of whom 3 537 were treated for 1 year or more and over 2 800 were treated for 2 years or more, pravastatin is generally well tolerated. Adverse events, both clinical and laboratory, are usually mild and transient. In all clinical studies (controlled and uncontrolled), approximately 2% of patients were discontinued from treatment due to adverse experiences attributable to pravastatin.
All adverse drug events (possibly, probably or definitively related to the drug) reported in ³0.5% of patients in placebo-controlled studies of up to 6 years duration are presented.
The following additional events have occurred during long-term studies with pravastatin: pruritus, scalp hair abnormalities, skin dryness, abnormal stool, appetite change, chest pain (noncardiovascular), weakness, excess sweating, hot flashes, paresthesia, equilibrium disturbance, mood change, eye symptoms (including soreness, dryness or itching), tinnitus and impotence (see Precautions, Endocrine Function).
In the West of Scotland Study (see Indications) involving 6 595 patients treated with pravastatin (n=3 216) or placebo (n=3 203), the adverse event profile in the pravastatin group was comparable to that of the placebo group over the median 4.8 years of the study.
The following have also been reported with other statins: hepatitis, cholestatic jaundice, anorexia, psychic disturbances including anxiety, hypospermia and hypersensitivity (see Precautions).
Lens: See Precautions.
Laboratory Test Abnormalities: Increases in serum transaminases and in creatine phosphokinase (CPK) in patients treated with pravastatin have been discussed (see Warnings).
Symptoms And Treatment Of Overdose: Symptoms: There have been 2 reports of overdosage with pravastatin, both of which were asymptomatic and not associated with clinical laboratory abnormalities. tag_Treatment
Treatment: In the event of overdosage, treatment should be symptomatic and supportive, and appropriate therapy instituted. Until further experience is obtained, no specific therapy of overdosage can be recommended. The dialyzability of pravastatin and its metabolites is not known.
Dosage And Administration: Prior to initiating pravastatin, the patient should be placed on at least an equivalent of the AHA Step I diet, which should be continued during treatment. If appropriate, a program of weight control and physical exercise should be implemented.
Hypercholesterolemia and Coronary Heart Disease: The recommended starting dose is 10 to 20 mg once daily at bedtime. If serum cholesterol is markedly elevated [e.g., Total Cholesterol greater than 7.75 mmol/L (300 mg/dL)] dosage may be initiated at 40 mg/day. Pravastatin may be taken without regard to meals.
Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed and dosage adjusted according to the patient’s response to therapy. Consideration should be given to reducing the dosage of pravastatin if cholesterol levels fall below the targeted range, such as that recommended by the Second Report of the U.S. National Cholesterol Education Program (NCEP). The recommended dosage range is 10 to 40 mg administered once a day at bedtime.
Concomitant Therapy: Some patients may require combination therapy with one or more lipid-lowering agents. Pharmacokinetic interaction with pravastatin administered concurrently with nicotinic acid, probucol, or gemfibrozil did not statistically significantly affect the bioavailability of pravastatin. The combined use of pravastatin and fibrates should however generally be avoided (see Warnings, Muscle Effects). No results are available from clinical studies involving the concomitant administration of pravastatin with probucol.
The lipid-lowering effects of pravastatin on Total and Low Density Lipoprotein Cholesterol are additive when combined with a bile acid-binding resin. However, when administering a bile acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, pravastatin should not be administered concomitantly, but should be given either 1 hour or more before or at least 4 hours following the resin (see Precautions, Drug Interactions, Concomitant Therapy with Other Lipid Metabolism Regulators).
Availability And Storage: 10 mg: Each pink to peach, rounded, rectangular-shaped, biconvex tablet, with a P embossed on one side and PRAVACHOL 10 engraved on the other, contains: pravastatin sodium 10 mg. Nonmedicinal ingredients: croscarmellose sodium, lactose, magnesium oxide, magnesium stearate, microcrystalline cellulose, povidone and red ferric oxide. Bottles of 100. Packages of 30 and 100 individually foil wrapped tablets.
20 mg: Each yellow, rounded, rectangular-shaped, biconvex tablet, with a P embossed on one side and PRAVACHOL 20 engraved on the other, contains: pravastatin sodium 20 mg. Nonmedicinal ingredients: croscarmellose sodium, lactose, magnesium oxide, magnesium stearate, microcrystalline cellulose, povidone and yellow ferric oxide. Bottles of 100. Packages of 30 and 100 individually foil wrapped tablets.
40 mg: Each green, rounded, rectangular-shaped, biconvex tablet, with a P embossed on one side and PRAVACHOL 40 engraved on the other, contains: pravastatin sodium 40 mg. Nonmedicinal ingredients: croscarmellose sodium, D&C yellow no. 10, FD&C blue no. 1, lactose, magnesium oxide, magnesium stearate, microcrystalline cellulose and povidone. Bottles of 100. Packages of 30 and 100 individually foil wrapped tablets.
Store at room temperature (15 to 30°C). Protect from moisture and light. (Shown in Product Recognition Section)
PRAVACHOL® Squibb Pravastatin Sodium Lipid Metabolism Regulator
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