Class: HMG-CoA Reductase Inhibitors
- Statins
VA Class: CV350
Chemical Name: [1S-[1α(βS*,δS*),2α,6α,8β(R*),8aα]]-1,2,6,7,8,8a-Hexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid monosodium salt
CAS Number: 81131-70-6
Brands: Pravachol

Medically reviewed by Drugs.com on Dec 13, 2021. Written by ASHP.

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).

Uses for Pravastatin

Reduction in Risk of Cardiovascular Events

Adjunct to nondrug therapies (i.e., lifestyle modifications) in patients with hypercholesterolemia without clinical evidence of CHD to reduce the risk of MI, to reduce the risk of undergoing myocardial revascularization procedures, and to reduce the risk of cardiovascular mortality (with no increase in death from noncardiovascular causes).

Adjunct to diet and lifestyle modifications in patients with clinical evidence of CHD to reduce the risk of total mortality by reducing coronary death, to reduce the risk of MI, to reduce the risk of undergoing myocardial revascularization procedures, and to reduce the risk of stroke or TIA.

Adjunct to diet and lifestyle modifications in patients with clinical evidence of CHD to slow the progression of coronary atherosclerosis.

Extensive evidence demonstrates that statins can substantially reduce LDL-cholesterol concentrations and associated risk of atherosclerotic cardiovascular disease (ASCVD) when used for secondary prevention or primary prevention in high-risk patients.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of ASCVD risk reduction. Patients with established ASCVD or high risk of ASCVD should also be treated with a statin.

Because relative ASCVD risk reduction is correlated with degree of LDL-cholesterol lowering, use maximum tolerated intensity of a statin to achieve greatest benefit. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is recommended; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%). AHA/ACC considers pravastatin 40–80 mg daily to be a moderate-intensity statin.

The addition of a nonstatin drug (e.g., ezetimibe, PCSK9 inhibitor) to statin therapy may be considered in certain high-risk patients who require further reduction in LDL-cholesterol concentrations, particularly if there is evidence from randomized controlled studies suggesting that the addition of the nonstatin drug further reduces ASCVD events.

When considering whether to initiate statin therapy for primary prevention, AHA/ACC recommends an individualized approach and shared decision making between patient and clinician. According to the guidelines, statin therapy may be considered in certain high-risk groups such as adults 20–75 years of age with LDL cholesterol ≥190 mg/dL, adults 40–75 years of age with diabetes mellitus, adults 40–75 years of age without diabetes mellitus but with LDL-cholesterol levels ≥70 mg/dL and an estimated 10-year ASCVD risk ≥7.5%, and adults 40–75 years of age with chronic kidney disease (not treated with dialysis or transplantation) and LDL-cholesterol concentrations of 70–189 mg/dL who have a 10-year ASCVD risk ≥7.5%.

Dyslipidemias

Adjunct to nondrug therapies (e.g., dietary management) in adults to decrease elevated serum total and LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia or mixed dyslipidemia (Fredrickson type IIa or IIb). Also used in combination with fenofibrate to decrease triglyceride concentrations and increase HDL-cholesterol concentrations in patients with mixed dyslipidemia and CHD (or CHD risk equivalents) who are on optimal statin therapy; however, no incremental benefit on cardiovascular morbidity and mortality beyond that provided by statin monotherapy.

Adjunct to dietary therapy and lifestyle modification in the management of heterozygous familial hypercholesterolemia in children ≥8 years of age who, despite an adequate trial of dietary management, have a serum LDL-cholesterol concentration of ≥190 mg/dL or a serum LDL-cholesterol concentration of ≥160 mg/dL and either a family history of premature cardiovascular disease or ≥2 other cardiovascular risk factors.

Adjunct to nondrug therapies (e.g., dietary management) in the treatment of primary dysbetalipoproteinemia (Fredrickson type III) in patients who do not respond adequately to diet.

Adjunct to nondrug therapies (e.g., dietary management) in the treatment of elevated serum triglyceride concentrations (Fredrickson type IV).

Reduction of total and LDL-cholesterol concentrations in patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus† (diabetic dyslipidemia), cardiac† or liver† transplantation, or nephrotic syndrome† (nephrotic hyperlipidemia).

Pravastatin Dosage and Administration

General

Patient Monitoring

Antilipemic Therapy

• Manufacturer recommends obtaining lipoprotein concentrations within 4 weeks following initiation of pravastatin and adjusting dosage accordingly. AHA/ACC cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy and after dosage changes (to assess response and adherence); monitoring should continue every 3–12 months thereafter as clinically indicated.

• Periodically reinforce adherence to lifestyle modifications. Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of ASCVD.

Administration

Oral Administration

Administer orally at any time of day without regard to meals.

Dosage

Available as pravastatin sodium; dosage expressed in terms of pravastatin.

Dosage modifications may be necessary when used concomitantly with certain drugs (see Specific Drugs under Interactions).

Pediatric Patients

Dyslipidemias

Oral

Children 8–13 years of age: 20 mg once daily. Dosages >20 mg daily have not been evaluated.

Adolescents 14–18 years of age: 40 mg once daily. Dosages >40 mg daily have not been evaluated.

Re-evaluate in adulthood and modify therapy appropriately.

Adults

Reduction in Risk of Cardiovascular Events

Oral

Use maximally tolerated statin intensity to achieve optimal ASCVD risk reduction. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is preferred; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%).

The AHA/ACC guideline panel considers pravastatin 40–80 mg daily to be a moderate-intensity statin.

Dyslipidemias

Oral

Initially, 40 mg once daily. If antilipemic response is inadequate, increase dosage to 80 mg daily. Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Use with caution in patients who consume substantial amounts of alcohol, have a recent (<6 months) history of liver disease, or exhibit manifestations of liver disease (e.g., unexplained increases in aminotransferase concentrations, jaundice).

Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.

Renal Impairment

Initially, 10 mg once daily in patients with severe renal impairment.

Cautions for Pravastatin

Contraindications

• Active liver disease or unexplained, persistent elevations of serum aminotransferases.

• Lactation.

• Known hypersensitivity to pravastatin or any ingredient in the formulation.

Warnings/Precautions

Musculoskeletal Effects

Myopathy (manifested as muscle pain, tenderness, or weakness and serum creatine kinase [CK, creatine phosphokinase, CPK] concentration increases >10 times the ULN) reported occasionally.

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in S_cr [usually accompanied by brown urine and urinary myoglobinuria]) with acute renal failure secondary to myoglobinuria has been reported.

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins. Characterized by proximal muscle weakness and elevated CK concentrations that persist despite discontinuance of statin therapy, necrotizing myopathy without substantial inflammation, and improvement following therapy with immunosuppressive agents.

Risk of myopathy is increased in patients receiving higher dosages of statins; risk also may be increased in geriatric patients (≥65 years of age) and patients with renal impairment or uncontrolled hypothyroidism.

Certain drug interactions also may increase risk of myopathy and/or rhabdomyolysis. (See Specific Drugs under Interactions.)

AHA/ACC recommends measurement of CK levels in patients with severe statin-associated muscle symptoms; however, routine monitoring not useful.

Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation in CK. Discontinue if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected.

Temporarily withhold therapy 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; uncontrolled seizures).

Hepatic Effects

Associated with increases in serum aminotransferase (AST, ALT) concentrations.

Pancreatitis, hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma, and fatal and nonfatal hepatic failure have been reported.

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage ). Serious statin-related liver injury is rare and unpredictable, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury. AHA/ACC cholesterol management guideline states that it is reasonable to obtain liver function tests in patients with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera); however, routine monitoring not recommended.

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt pravastatin therapy. If an alternate etiology is not found, do not restart pravastatin.

Hyperglycemic Effects

Increases in HbA_1c and fasting serum glucose concentrations reported. Possible increased risk of developing diabetes. May need to monitor glucose concentrations following initiation of statin therapy.

AHA/ACC cholesterol management guideline states that in patients with increased risk of diabetes mellitus or new-onset diabetes mellitus, statin therapy and lifestyle modifications should be continued to reduce risk of ASCVD.

Endogenous Steroid Production

Statins interfere with cholesterol synthesis and theoretically may blunt adrenal and/or gonadal steroid production.

Effects of pravastatin on basal steroid hormone levels not established. Effects on pituitary-gonadal axis in premenopausal women unknown.

If clinical evidence of endocrine dysfunction is present, evaluate patients appropriately.

Caution advised if a statin or another antilipemic agent is used concomitantly with drugs that may decrease concentrations or activity of endogenous steroid hormones (e.g., ketoconazole, spironolactone, cimetidine).

Cognitive Impairment

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) reported rarely.

Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy). Not associated with fixed or progressive dementia (e.g., Alzheimer’s disease) or clinically important cognitive decline. Not associated with any specific statin, patient's age, statin dosage, or concomitant drug therapy.

FDA states that cardiovascular benefits of statins outweigh the small increased risk of cognitive impairment.

If manifestations consistent with cognitive impairment occur, National Lipid Association (NLA) statin safety assessment task force recommends evaluating and managing patients appropriately.

Role as Adjunct Therapy

Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.

Specific Populations

Pregnancy

All statins were previously contraindicated in pregnant women because fetal risk was thought to outweigh any possible benefit. However, the totality of evidence to date indicates limited potential for statins to cause malformations and other adverse embryofetal effects; FDA has therefore requested removal of the contraindication. Most pregnant patients should still discontinue statins because of the possibility of fetal harm; however, some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) may benefit from continued therapy. Consider patient's individual risks and benefits.

Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician; clinician should advise patient on the appropriate course of action.

Increased risk of miscarriage reported in pregnant women exposed to statins; however, not clear whether drug-related or due to other confounding factors.

Lactation

Distributed into milk; effects of drug on breast-fed infants or milk production not known. Use contraindicated in nursing women; women who require pravastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.

Pediatric Use

Safety and efficacy not established in children <8 years of age. Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.

Use with caution, since age ≥65 years is a predisposing factor for myopathy.

Patients >75 years of age may have a higher risk of adverse effects and lower adherence to therapy; consider expected benefits versus adverse effects before initiating statin therapy in this population.

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol, have a recent (<6 months) history of liver disease, or exhibit manifestations of liver disease (e.g., unexplained increases in aminotransferase concentrations, jaundice).

Contraindicated in patients with active liver disease or unexplained, persistent increases in liver function test results.

Renal Impairment

Monitor closely for adverse musculoskeletal effects, since history of renal impairment may be a risk factor for development of rhabdomyolysis.

Dosage adjustments necessary in patients with severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Musculoskeletal pain, nausea or vomiting, upper respiratory infection, diarrhea, headache.

Interactions for Pravastatin

Minimally metabolized by CYP3A4; pharmacokinetic interaction unlikely.

Specific Drugs

Pravastatin Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver. Mean peak plasma concentrations occur at 1–1.5 hours.

Absolute bioavailability is 17%.

Evening administration of the drug is associated with a decrease in the extent of absorption; however, the antilipemic activity remains unchanged and may be superior to the activity achieved with morning administration.

Onset

A therapeutic response to pravastatin is usually apparent within 1 week after initiating therapy, with a maximal response occurring within 4 weeks.

Food

Food appears to reduce the systemic bioavailability of pravastatin; however, antilipemic effects are similar whether pravastatin is administered with or 1 hour prior to meals.

Distribution

Extent

Distributed mainly to the liver.

Distributed into human milk.

Plasma Protein Binding

Approximately 50%.

Elimination

Metabolism

Undergoes enzymatic and nonenzymatic biotransformation independent of the CYP enzyme system. The principal metabolites are pharmacologically inactive.

Elimination Route

Excreted in urine (20%) and feces (70%).

Half-life

1.8 hours.

Special Populations

Renal impairment may reduce clearance of pravastatin and/or active metabolites.

Hepatic impairment may reduce clearance of pravastatin and/or active metabolites.

Stability

Storage

Oral

Tablets

Tight containers at 25°C (may be exposed to 15–30°C); protect from light and moisture.

Actions

• Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis. Reduces serum concentrations of total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglycerides.

• Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries, modulate blood pressure in hypercholesterolemic patients with hypertension, and possess anti-inflammatory activity.

Advice to Patients

• Importance of adhering to nondrug therapies and measures, including adherence to a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight.

• Risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages or when used concomitantly with certain drugs. Importance of patients promptly reporting muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, or if manifestations persist after discontinuance of therapy.

• Risk of adverse hepatic effects. Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).

• Risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).

• Risk of increased glucose concentrations and development of type 2 diabetes. May need to monitor glucose concentrations following initiation of statin therapy.

• Importance of advising women to notify their clinician if they become pregnant during therapy.

• Importance of avoiding breast-feeding during therapy.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• What are the side effects of statins?
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