Brand name: Altoprev
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 Lovastatin

Reduction in Risk of Cardiovascular Events

Adjunct to diet and lifestyle modifications in patients without symptomatic cardiovascular disease who have normal or moderate elevations of total and LDL-cholesterol and below-average HDL-cholesterol concentrations to reduce the risk of MI or unstable angina and to reduce the risk of undergoing coronary revascularization procedures.

Adjunct to nondrug therapies (e.g., dietary management) in patients with CHD to slow the progression of coronary atherosclerosis as part of a treatment strategy to lower total and LDL-cholesterol concentrations to target levels.

Extensive evidence demonstrates that statins can substantially reduce LDL-cholesterol concentrations and associated risk of atherosclerotic cardiovascular disease (ASCVD); may be 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 lovastatin 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) 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, including heterozygous familial and non-familial hypercholesterolemia and mixed dyslipidemia (e.g., Frederickson types IIa and IIb.

Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and girls (≥1 year postmenarchal) 10–17 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. Safety and efficacy of lovastatin extended-release not established in children or adolescents <20 years of age.

Reduction of elevated LDL-cholesterol concentrations in patients with combined hypercholesterolemia and hypertriglyceridemia caused by genotypic familial combined hyperlipidemia; however, has not been studied in conditions where the major abnormality is elevation of chylomicrons, very-low density lipoproteins (VLDLs), or intermediate-density lipoproteins (IDLs).

Lovastatin Dosage and Administration

General

Pretreatment Screening

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

• 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.

• Monitor for signs and symptoms of immune-mediated necrotizing myopathy (i.e., proximal muscle weakness, elevated serum CK) which persist despite discontinuation of statin treatment.

• Evaluate patients who develop clinical evidence of endocrine dysfunction.

Administration

Oral Administration

Administer orally.

Immediate-release Tablets

Administer with the evening meal.

Extended-release Tablets

Administer in the evening at bedtime.

Dosage

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

Pediatric Patients

Dyslipidemias

Immediate-release Tablets

Oral

Children 10–17 years of age who require reductions in LDL-cholesterol of ≥20%: Initially, 20 mg once daily.

Children 10–17 years of age who require small reductions in LDL-cholesterol: Consider initial dosage of 10 mg once daily.

Recommended dosage range is 10–40 mg daily; maximum recommended dosage is 40 mg daily.

Adults

Reduction in Risk of Cardiovascular Events

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 lovastatin 40–80 mg daily to be a moderate-intensity statin.

Immediate-release Tablets

Oral

Initially, 20 mg once daily with evening meal. Recommended dosing range is 10–80 mg/day in a single dose or 2 divided doses; maximum recommended total daily dose is 80 mg.

Extended-release Tablets

Oral

Recommended dosage range is 20-60 mg once daily in the evening.

Dyslipidemias

Immediate-release Tablets

Oral

Usual initial dosage is 20 mg once daily with the evening meal.

Patients who require reductions in LDL-cholesterol concentrations of ≥20%: Initially, 20 mg once daily.

Patients who require smaller reductions in LDL-cholesterol: Consider initial dosage of 10 mg once daily.

Recommended dosage range is 10–80 mg daily given in 1 or 2 divided doses; maximum recommended dosage is 80 mg daily.

Extended-release Tablets

Oral

Recommended dosage range is 20–60 mg once daily in the evening.

Special Populations

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 disease or unexplained, persistent increases in serum aminotransferase concentrations.

No specific dosage recommendations.

Renal Impairment

Immediate-release tablets: Use with caution in patients with severe renal impairment (Cl_cr <30 mL/min). Carefully consider dosage increases >20 mg daily in such patients; if deemed necessary, implement with extreme caution.

Extended-release tablets: Use dosages >20 mg daily in patients with severe renal impairment only after careful consideration of the expected benefits versus potential risks of myopathy and rhabdomyolysis.

Geriatric Patients

Immediate-release tablets: Dosage adjustment based on age-related pharmacokinetic differences not necessary.

Extended-release tablets: Usual initial dosage in patients ≥65 years of age is 20 mg once daily; use higher dosages only after careful consideration of potential risks and benefits.

Pharmacogenomic Considerations

Patients with solute carrier organic anion transporter (SLCO) 1B1 decreased or possible decreased function phenotype: Limit lovastatin dosage to ≤20 mg/day.

Patients with SLCO1B1 poor function phenotype: Alternative statin recommended.

Cautions for Lovastatin

Contraindications

• Hypersensitivity to lovastatin or any component of the formulation.

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

• Concomitant therapy with strong inhibitors of CYP3A4 (e.g., clarithromycin, cobicistat-containing preparations, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, voriconazole).

• Nursing mothers. Manufacturer states that lovastatin is contraindicated in women who are pregnant or may become pregnant; however, because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins.

Warnings/Precautions

Musculoskeletal Effects

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

Rhabdomyolysis (characterized by muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever) with or without acute renal failure secondary to myoglobinuria reported; rare fatalities have occurred.

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

Certain drug or food 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.

Discontinue if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected. Periodic CK determinations may be considered (baseline or when dosage increased), but there is no assurance that such monitoring will prevent myopathy.

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

Immune-Mediated Necrotizing Myopathy

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, positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy without substantial inflammation, and improvement following therapy with immunosuppressive agents.

Additional neuromuscular and serologic testing may be necessary.

The risk of IMNM should be considered carefully prior to initiating therapy with another statin; monitor for signs and symptoms.

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 lovastatin.

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 required.

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of chronic liver disease. Contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.

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

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.

Endogenous Steroid Production

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

No effects on basal plasma cortisol concentrations, testosterone concentrations, or adrenal reserve observed with lovastatin. Effects on male fertility or on pituitary-gonadal axis in premenopausal women not fully established.

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., spironolactone, cimetidine).

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

Not known whether lovastatin is distributed into human milk; however, other statins are distributed into milk. Use is contraindicated in nursing women; women who require lovastatin 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 Makes of Reproductive Potential

Effects on male fertility or on pituitary-gonadal axis in premenopausal women not fully established.

May cause fetal harm when administered to a pregnant woman; sexually active women (including adolescents) of childbearing age should be counseled to use a reliable form of contraception.

Pediatric Use

Safety and efficacy of immediate-release tablets not established in children <10 years of age or in prepubertal children. Experts state statins may be considered in patients as young as 8 years of age in the presence of concerning family history, extremely elevated LDL-cholesterol level, or elevated lipoprotein (a), in the context of informed shared decision-making and counseling with the patient and family.

Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.

Safety and efficacy of extended-release lovastatin not established in children or adolescents <20 years of age.

Geriatric Use

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

Immediate-release preparation: Mean plasma HMG-CoA reductase inhibitory activity is approximately 45% higher in patients 70–78 years of age than in young adults; however, dosage adjustment based on age-related pharmacokinetic differences not necessary in geriatric patients. Because advanced age (≥65 years of age) is a predisposing factor for myopathy, including rhabdomyolysis, use with caution in this population.

Extended-release preparation: Safety and efficacy appear to be similar to those in younger adults; however, greater sensitivity in some older patients cannot be ruled out. Use with caution.

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 disease or unexplained, persistent increases in liver function test results.

Renal Impairment

Mean plasma levels of HMG-CoA reductase inhibitory activity after a single dose of lovastatin were approximately 2-fold higher in patients with severe renal impairment (Cl_cr10–30 mL/minute) than in healthy volunteers.

Immediate-release preparation: Use with caution in patients with severe renal impairment (Cl_cr <30 mL/minute); dosage increases >20 mg daily should be carefully considered and, if deemed necessary, implemented cautiously.

Extended-release preparation: Dosage increases >20 mg daily should only be considered in patients with severe renal impairment if the expected benefits exceed the increased risk of myopathy and rhabdomyolysis.

Because many patients who have developed rhabdomyolysis during lovastatin therapy have had complicated medical histories, including renal impairment secondary to chronic diabetes mellitus, closely monitor such patients.

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 potential for 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 or possible decreased function phenotype or poor function phenotypes will have increased exposure and risk of statin-associated musculoskeletal symptoms. Lower doses or an alternative statin may be required.

Common Adverse Effects

Common adverse effects (≥2%) in patients receiving immediate-release tablets: GI disturbances (e.g., flatulence, diarrhea, abdominal pain, constipation, nausea, dyspepsia), headache, myalgia.

Common adverse effects (≥5%) in patients receiving extended-release tablets: infection, headache, accidental injury.

Drug Interactions

Metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.

Substrate of P-gp and organic anion transporter protein (OATP).

Drug interaction studies not been performed with extended-release preparation; use caution extrapolating data from immediate-release preparation studies.

Drugs Affecting Hepatic Microsomal Enzymes

Strong CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma lovastatin concentrations); increased risk of myopathy or rhabdomyolysis. Concomitant use contraindicated.

Drugs Affecting or Affected by Transport Systems

P-gp inhibitors: Potential pharmacokinetic interaction (increased exposure); increased risk of statin-induced toxicity.

OATP1B1 inhibitors: Potential pharmacokinetic interaction (increased exposure); increased risk of statin-induced toxicity.

Specific Drugs and Foods

Lovastatin Pharmacokinetics

Absorption

Bioavailability

Immediate-release tablets: Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver. Peak plasma concentrations attained at 2–4 hours.

Immediate-release tablets: Absolute bioavailability is <5%.

Extended-release tablets: Slower and more prolonged appearance of lovastatin in plasma; peak plasma concentrations delayed (attained at about 14 hours) and lower compared with immediate-release tablets.

Extended-release tablets: More bioavailable (in terms of lovastatin) than immediate-release tablets; however, bioavailability of total and active HMG-CoA reductase inhibitors is similar between the 2 formulations. Exposure with extended-release 60 mg is greater than that with immediate-release 80 mg.

Food

Immediate-release tablets: Food increases bioavailability; under fasting conditions, plasma concentrations of total inhibitors approximately two-thirds those found when administered with a meal.

Extended-release tablets: Food decreases bioavailability; plasma concentrations (lovastatin and lovastatin acid) approximately 0.5–0.6 times those found when administered without food.

Onset

Therapeutic response usually is apparent within 2 weeks; maximal response occurs within 4–6 weeks.

Distribution

Extent

Distributed mainly to the liver; crosses the blood-brain barrier.

Lovastatin crosses the placenta. Not known whether distributed into human milk.

Plasma Protein Binding

>95%.

Elimination

Metabolism

Metabolized by CYP3A4. Lovastatin has active metabolites.

Elimination Route

Excreted in urine (10%) and feces (83%).

Special Populations

Plasma concentrations of total inhibitors increased 2-fold in patients with severe renal impairment (Cl_cr 10–30 mL/min) compared with healthy individuals following a single dose (immediate-release).

Mean plasma levels of HMG-CoA reductase inhibitory activity approximately 45% higher in geriatric patients (70–78 years of age) than in younger adults (18–30 years of age).

Patients with certain SLCO1B1 phenotypes (i.e., decreased, possible decreased, or poor function) will have increased lovastatin exposure compared to those with normal function.

Stability

Storage

Oral

Immediate-release Tablets

20–25°C; protect from light.

Extended-release Tablets

20–25°C (excursions permitted to 15–30°C). Avoid excessive heat and humidity.

Actions

• Prodrug requiring hydrolysis in vivo for activity.

• 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 (i.e., 80 mg daily) or when used concomitantly with certain drugs or grapefruit juice. Advise patients to promptly report unexplained 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. Advise patients to promptly report 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 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 during therapy.

• Advise women not to breastfeed during treatment with lovastatin.

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

• Advise 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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