Drug class: HMG-CoA Reductase Inhibitors

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

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

Uses for Pravastatin Sodium

Reduction in Risk of Cardiovascular Events

Adjunct to diet and lifestyle modifications in adults with elevated LDL-cholesterol without clinical evidence of CHD to reduce the risk of MI, myocardial revascularization procedures, and cardiovascular mortality.

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

Extensive evidence demonstrates that statins can substantially reduce LDL-cholesterol concentrations and associated risk of atherosclerotic cardiovascular disease (ASCVD) when used for secondary 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 LDL-cholesterol concentrations in the treatment of adults with primary hyperlipidemia.

Adjunct to dietary therapy to reduce LDL-cholesterol in children ≥8 years of age with heterozygous familial hypercholesterolemia.

Adjunct to nondrug therapies (e.g., dietary management) in the treatment of adults with primary dysbetalipoproteinemia.

Adjunct to nondrug therapies (e.g., dietary management) in the treatment of adults with hypertriglyceridemia.

Pravastatin Sodium Dosage and Administration

General

Pretreatment Screening

• Obtain baseline liver enzyme tests (e.g., AST, ALT).

• Obtain baseline hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain baseline lipid panel.

Patient Monitoring

• Perform fasting lipid panel periodically 4–12 weeks after statin initiation or dose adjustment; 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.

• Perform repeat liver function tests (e.g., AST, ALT, total bilirubin, alkaline phosphatase) when clinically indicated (i.e., symptoms suggesting hepatotoxicity); routine monitoring in the absence of symptoms is not recommended.

• Monitor hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain creatine kinase (CK) levels in patients with severe statin-associated muscle weakness; routine monitoring in the absence of symptoms is not recommended.

Administration

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

Dosage

Dosage modifications may be necessary when used concomitantly with certain drugs.

Pediatric Patients

Dyslipidemias

Oral

Children 8–13 years of age: 20 mg once daily. Dosages >40 mg daily have not been evaluated.

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

Adults

Reduction in Risk of Cardiovascular Events

Oral

Initially, 40–80 mg once daily. 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 or 80 mg once 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.

Renal Impairment

Initially, 10 mg once daily in patients with severe renal impairment; maximum dosage 40 mg once daily.

Geriatric Patients

No specific dosage recommmendations. Cautious dose selection recommended.

Pharmacogenomic Considerations

SLCO1B1 poor function phenotype: Initial dosage ≤40 mg/day.

Cautions for Pravastatin Sodium

Contraindications

• Hypersensitivity to pravastatin or any component in the formulation.

• Active liver failure or decompensated cirrhosis.

Warnings/Precautions

Musculoskeletal Effects

Myopathy (manifested as muscle pain, tenderness, or weakness and serum creatine kinase [CK] concentration increases) reported occasionally.

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

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.

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; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).

Advise patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

Immune-mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely. Characterized by proximal muscle weakness and elevated CK concentrations that persist despite discontinuance of statin therapy, positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement following therapy with immunosuppressive agents. Discontinue pravastatin if IMNM suspected.

Hepatic Effects

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

Rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin.

Consider liver enzyme tests before initiation of therapy and as clinically indicated. 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.

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease. Contraindicated in patients with acute liver failure or decompensated cirrhosis.

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt pravastatin therapy.

Hyperglycemic Effects

Increases in HbA_1c and fasting serum glucose concentrations reported. Possible increased risk of developing diabetes.

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.

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 human milk; effects of drug on breast-fed infants or milk production not known. Use not recommended 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.

Females and Males of Reproductive Potential

AHA/ACC cholesterol management guideline states women (including adolescents) of childbearing age who are sexually active should be counseled to use a reliable form of contraception.

Pediatric Use

Safety and effectiveness in pediatric patients ≥8 years of age with heterozygous familial hypercholesterolemia (HeFH) established. Dosages >40 mg daily not studied in this population.

Safety and efficacy not evaluated in pediatric patients with other types of hyperlipidemia.

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 and/or have a history of liver disease.

Contraindicated in patients with active liver failure or decompensated cirrhosis.

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.

Pharmacogenomic Considerations

Genetic variation in the solute carrier organic anion transporter (SLCO) family member (SLCO1B1), ABCG2 (also known as breast cancer resistance protein [BCRP]), and CYP2C9 genes alter systemic exposure to statins, which can increase the risk for statin-associated musculoskeletal symptoms.

In patients with phenotypes that result in increased statin exposure, consider other patient-specific issues that may increase statin exposure (e.g., renal and hepatic function, drug-drug interactions).

Experts state statin therapy should neither be discontinued nor avoided based on SLCO1B1, ABCG2, or CYP2C9 genotype results for patients with an indication for statin therapy.

Patients with SLCO1B1 decreased, possible decreased, or poor function phenotypes will have increased exposure and risk of statin-associated musculoskeletal symptoms.

Common Adverse Effects

Common adverse effects (≥2% and more than placebo): musculoskeletal pain, nausea/vomiting, upper respiratory infection, diarrhea, headache.

Drug Interactions

Does not undergo CYP metabolism; pharmacokinetic interaction unlikely.

Substrate of organic anion transporter protein (OATP) 1B1, 1B3, and 2B1.

Drugs Affecting or Affected by Transport Systems

OATP1B1, 1B3, or 2B1 inhibitors: Possible increased exposure and increased risk of statin-induced toxicity (e.g., myopathy).

Specific Drugs

Pravastatin Sodium 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

Therapeutic response 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 isomerization and hydroxylation independent of the CYP enzyme system. One metabolite has 1/10th–1/40th the HMG-CoA reductase inhibitory activity of the parent compound.

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.

Exposure may be increased in geriatric individuals compared with younger adults.

Patients with certain solute carrier organic anion transporter (SLCO) 1B1 phenotypes (i.e., decreased, possible decreased, or poor function) will have increased pravastatin exposure compared to those with normal function.

Stability

Storage

Oral

Tablets

20-25°C in tight containers; 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.

• Other favorable (pleitropic) effects include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.

Advice to Patients

• Advise patients of the 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.

• Advise patients of the risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages or when used concomitantly with certain drugs. Stress 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.

• Advise patients of the risk of adverse hepatic effects and the importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).

• Advise patients of the risk of increased glucose concentrations and development of type 2 diabetes.

• Advise patients that pravastatin tablets may be administered as a single dose at any time of day, with or without food.

• Advise females of reproductive potential (including adolescents) of the risk to a fetus and to use effective contraception during treatment. Advise women to notify their clinician if they become pregnant or suspect pregnancy during therapy.

• Advise women not to breastfeed during therapy.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

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