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.

Prevention of Cardiovascular Disease:

• In hypercholesterolemic patients without clinically evident coronary heart disease (CHD), PRAVACHOL (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, PRAVACHOL 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

Hyperlipidemia:

PRAVACHOL 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)
• 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

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

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.

PRAVACHOL may be used with bile acid resins. When administering a bile-acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, PRAVACHOL should be given either 1 hour or more before or at least 4 hours following the resin.

In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily.

PRAVACHOL is contraindicated in patients with:

• Active liver disease or unexplained persistent elevations of serum transaminases
• Women who are pregnant or may become pregnant and nursing mothers

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.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. 

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.

Statins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function.

Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production.

Cases of myopathy, including rhabdomyolysis, have been reported with pravastatin coadministered with colchicine, and caution should be exercised when prescribing pravastatin with colchicine.

The risk of myopathy during treatment with statins is increased with concurrent therapy with either erythromycin, cyclosporine, niacin, or fibrates.

In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily.

Other macrolides (e.g., erythromycin and azithromycin) have the potential to increase statin exposures while used in combination. Pravastatin should be used cautiously with macrolide antibiotics due to a potential increased risk of myopathies.

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.

Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are coadministered with gemfibrozil, concomitant administration of PRAVACHOL with gemfibrozil should be avoided.

The risk of skeletal muscle effects may be enhanced when pravastatin is used in combination with niacin; a reduction in PRAVACHOL dosage should be considered in this setting.

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.

Pravastatin is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require PRAVACHOL treatment should not breastfeed their infants.

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• Use in patients under the age of 8. GoToSource

• Lessen ischemic neurological deficits after aneurysmal subarachnoid hemorrhage. GoToSource

• Refractory chronic graft-versus-host disease. GoToSource

• Systemic sclerosis. GoToSource

• Non-alcoholic fatty liver disease and nonalcoholic steatohepatitis. GoToSource

• Prevention of preeclampsia. GoToSource

• Reduce recurrent urinary tract infections. GoToSource

• Treatment of gallstones. GoToSource

Rhabdomyolysis (breakdown of muscle tissue). GoToSource

New-onset diabetes mellitus. GoToSource

Myopathy. GoToSource

Peripheral neuropathy (nerve damage) including mononeuropathy, gynecomastia (male breast enlargement), irritability and aggression, dyspnea (shortness of breath), pancreatitis (inflammation of the pancreas), drug eruption and colitis. GoToSource

Pollakiuria (daytime urinary frequency) and nocturia (excessive urination at night). GoToSource

Cognitive and memory impairments; sleep disturbance, impotence and decreased libido. GoToSource

Amyotrophic lateral sclerosis (ALS)-like conditions. GoToSource

Liver injury. GoToSource

Lawsuits filed for rhabdomyolysis, kidney damage and type 2 diabetes.