section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Lovastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin), is an antilipemic agent.4,5,118,119

Uses ⬆ ⬇

[Section Outline]

Reduction in Risk of Cardiovascular Events !!navigator!!

Primary Prevention

Lovastatin is used as an adjunct to diet and lifestyle modifications in patients without symptomatic cardiovascular disease who have normal or moderate elevations of total and low-density lipoprotein (LDL)-cholesterol and below average high-density lipoprotein (HDL)-cholesterol concentrations to reduce the risk of myocardial infarction (MI) or unstable angina and to reduce the risk of undergoing coronary revascularization procedures.118,119 Two oral preparations (immediate- and extended-release tablets) are available for such use.118,119

Efficacy and safety of lovastatin for this use were established in a randomized, double-blind, placebo-controlled study (Air Force/Texas Coronary Atherosclerosis Prevention Study [AFCAPS/TexCAPS]) in patients who had total and LDL-cholesterol concentrations averaging 221 and 150 mg/dL, respectively, and HDL-cholesterol concentrations averaging 36 mg/dL (men) or 40 mg/dL (women).118,119 Lovastatin (20-40 mg daily as immediate-release tablets) reduced the incidence of a first acute major event (i.e., primary end point defined as fatal or nonfatal MI, unstable angina, or sudden cardiac death) by 37% after an average follow-up period of 5.2 years.83,118,119 Lovastatin therapy also produced benefit in terms of secondary end points, including a 33% reduction in coronary revascularization procedures, a 32% reduction in unstable angina, a 40% reduction in the incidence of fatal or nonfatal MI, and a 25% reduction in cardiovascular (e.g., atherosclerotic) events.83,118,119

Reducing Progression of Coronary Atherosclerosis (Secondary Prevention)

Lovastatin is used as an adjunct to diet and lifestyle modifications in patients with coronary heart disease (CHD) to slow the progression of coronary atherosclerosis as part of a treatment strategy to lower total and LDL-cholesterol concentrations to target levels.118,119

Lovastatin has been shown to slow the progression of atherosclerosis in both coronary and carotid arteries by reducing intimal-wall thickness.61,70,74,75,76,92,93,118,119 In several double-blind, placebo-controlled studies (e.g., Canadian Coronary Atherosclerosis Intervention Trial [CCAIT], Monitored Atherosclerosis Regression Study [MARS], Familial Atherosclerosis Treatment Study [FATS]) in men and women with or without documented CHD and elevated lipoprotein concentrations, progression of atherosclerosis at 2-3 years (measured as the mean per-patient changes from baseline in mean and minimal coronary artery lumen diameters, percent diameter stenosis, and formation of new lesions) was reduced in patients who received recommended daily dosages of lovastatin.61,70,74,75,76,118,119

Clinical Perspective

The 2018 American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol management guideline emphasizes lifestyle modification as the foundation of atherosclerotic cardiovascular disease (ASCVD) risk reduction.400 If pharmacologic therapy is needed, hydroxymethyl-glutaryl-CoA (HMG-CoA) reductase inhibitor (statin) therapy is recommended.400 Statins are considered the first-line drugs of choice for reducing LDL-cholesterol, the lipoprotein fraction found to be a major cause of clinical ASCVD.400,401,402 There is extensive evidence demonstrating that statins can substantially reduce LDL-cholesterol concentrations and associated risk of ASCVD when used for secondary or primary prevention in high-risk patients.336,337,338,400,401,402 Because the relative risk reduction is correlated with the degree of LDL lowering, the maximum tolerated statin intensity should be used to achieve optimum ASCVD benefits.400,401,402

When considering whether to initiate statin therapy for primary prevention, the 2018 AHA/ACC cholesterol management guideline recommends a shared decision-making approach between the patient and clinician.400 The guideline recommends consideration of statin therapy in certain high-risk groups such as adults 20-75 years of age with LDL-cholesterol levels ≥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%.400,401

The guideline states that patients with clinical ASCVD (defined as those with acute coronary syndromes [ACS], history of MI, stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack [TIA], or peripheral artery disease [PAD], including those with aortic aneurysm) should be treated with a statin in conjunction with lifestyle modification to reduce LDL-cholesterol concentrations.400 Because patients >75 years of age may have a higher risk of adverse effects and lower adherence to therapy, the expected benefits versus adverse effects should be considered before initiating statin therapy in this population.400 The maximum tolerated intensity of a statin should be used to achieve optimum ASCVD benefits.400 AHA/ACC recommends the use of high-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by at least 50%).400 If high-intensity statin therapy is not possible (e.g., because of a contraindication or intolerable adverse effect), moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30-49%) may be used.400

Intensity of Statin Therapy

The appropriate intensity of a statin should be used to reduce the risk of ASCVD.400 Based on the average LDL-cholesterol response observed with specific statins and dosages used in the randomized controlled studies evaluated by the AHA/ACC guideline panel, lovastatin 40-80 mg daily is considered to be a moderate-intensity statin (producing approximate LDL-cholesterol reductions of 30-49%).400

Combination Antilipemic Therapy

The addition of a nonstatin drug (e.g., ezetimibe, PCSK9 inhibitor) to statin therapy may be useful in certain high-risk patients who experience an inadequate reduction in LDL-cholesterol concentrations despite maximally tolerated statin therapy (e.g., <50% reduction in LDL-cholesterol or LDL-cholesterol concentration ≥55 mg/dL or non-HDL-cholesterol ≥85 mg/dL).400,403 If combination therapy is necessary, selection of the nonstatin drug should be based on the risk and benefit profile (i.e., reduction in ASCVD risk outweighs the drug's potential for adverse effects and drug interactions) and patient preferences.400,403

A 2022 consensus decision pathway published by ACC addresses the use of nonstatin therapies for primary or secondary prevention of ASCVD.403 In patients with primary hypercholesterolemia without ASCVD who require additional LDL-lowering therapy despite maximal statin therapy, ezetimibe and/or a PCSK9 monoclonal antibody (mAb) inhibitor are considered preferred initial nonstatin therapies due to demonstrated benefits in cardiovascular outcomes.403 If therapeutic goals are not achieved, other nonstatin therapies (e.g., inclisiran, bempedoic acid, evinacumab, lomitapide) may be considered.403

In patients receiving statin therapy as secondary prevention who are at very high risk of ASCVD and require additional LDL-lowering therapy despite maximal statin therapy, ezetimibe and/or a PCSK9 inhibitor are considered preferred initial nonstatin therapies.403 In patients receiving statin therapy as secondary prevention who are not at very high risk of ASCVD, ezetimibe is considered the preferred initial nonstatin therapy, followed by addition or replacement with a PCSK9 inhibitor if additional LDL-lowering therapy is needed.403 If therapeutic goals are not achieved in the secondary prevention setting, inclisiran (in place of a PCSK9 inhibitor) or bempedoic acid may be considered.403

A 2022 scientific statement published by the National Lipid Association (NLA) addresses the use of nonstatin therapies for ASCVD risk reduction in patients with statin intolerance.406 Nonstatin LDL-lowering therapy may be considered in patients with complete or partial statin intolerance, including during the course of attempting to identify a tolerable alternate statin regimen in patients with high or very high ASCVD risk.406 When nonstatin therapies are used, agents that have demonstrated cardiovascular outcome benefit in randomized trials are preferred.406

Dyslipidemias !!navigator!!

Primary Hypercholesterolemia or Mixed Dyslipidemia

Lovastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated total and LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase HDL-cholesterol concentrations in patients with primary hypercholesterolemia (including heterozygous familial and non-familial hypercholesterolemia) and mixed dyslipidemia (e.g., Fredrickson types IIa and IIb).8,9,18,23,24,29,30,31,32,33,35,36,40,43,49,90,118,119

Lovastatin immediate-release tablets are specifically labeled for the reduction of elevated total cholesterol and LDL-cholesterol in patients with primary hypercholesterolemia (Types IIa and IIb).118 Lovastatin extended-release tablets are specifically labeled for the reduction of elevated total cholesterol, LDL-cholesterol, apo B, and triglycerides, and to increase HDL-cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb).119 The manufacturer of the extended-release tablets states that the drug has not been studied in Fredrickson Types I, III, and V.119

Although lovastatin also has been used to reduce elevated LDL-cholesterol concentrations in patients with combined hypercholesterolemia and hypertriglyceridemia caused by genotypic familial combined hyperlipidemia,18,19,31,50,118 the drug has not been studied in conditions where the major abnormality is elevation of chylomicrons, very-low-density lipoproteins (VLDLs), or intermediate-density lipoproteins (IDLs).118

Reductions in total and LDL-cholesterol produced by usual dosages of lovastatin substantially exceed those of placebo.4,5,31,32,118,119 In 2 multicenter, placebo-controlled studies, 89% of patients with heterozygous familial hypercholesterolemia or 97% of patients with other forms of primary hypercholesterolemia who received lovastatin 40 mg twice daily and dietary management had reductions in LDL-cholesterol of at least 20%, while 61 or 51% of such patients had LDL-cholesterol reductions of at least 40%; reductions in LDL-cholesterol averaged 39% in both groups of patients.31,32

Lovastatin was also evaluated in the double-blind, randomized EXCEL study in patients with hypercholesterolemia (total cholesterol 240-300 mg/dL, LDL cholesterol >160 mg/dL).118,119 Patients were randomized to receive lovastatin (20 or 40 mg once daily in the evening or 20 or 40 mg twice daily as immediate-release tablets) or placebo.118,119 Statistically significant dose-related reductions in total cholesterol (17-29% decrease) and LDL-cholesterol (24-40% decrease) were observed with lovastatin treatment.118,119 Comparable results were observed in a 6-month extension study of lovastatin extended-release tablets (40 or 60 mg once daily).119

Reductions in total and LDL-cholesterol concentrations produced by usual dosages of lovastatin generally appear to be similar to or greater than those produced by monotherapy with usual dosages of some statins (e.g., fluvastatin, pravastatin, simvastatin) but less than those produced by usual dosages of atorvastatin and rosuvastatin.95,375,400 In a randomized, multicenter, parallel-group study comparing the efficacy of various statins, patients with hypercholesterolemia who received lovastatin 20-80 mg daily experienced similar or greater reductions in total and LDL-cholesterol concentrations (21-36 and 29-48%, respectively) than those receiving fluvastatin 20-40 mg daily (13-19 and 17-23%, respectively), pravastatin 10-40 mg daily (13-24 and 19-34%, respectively), or simvastatin 10-40 mg daily (21-30 and 28-41%, respectively).95 However, atorvastatin dosages of 10-80 mg daily produced greater reductions in total and LDL-cholesterol concentrations (28-42 and 38-54%, respectively) than lovastatin.95

Limited data from comparative studies suggest that reductions in total and LDL-cholesterol concentrations produced by lovastatin are similar to or greater than those produced by certain other antilipemic agents (i.e., bile acid sequestrants, niacin, fibric acid derivatives).18,96,97,101 Lovastatin 40-80 mg daily reportedly has produced greater reductions in total cholesterol than cholestyramine 24 g daily.18,118,119 Lovastatin appears to produce greater reductions in total and LDL-cholesterol than niacin or fibric acid derivatives (i.e., fenofibrate, gemfibrozil) but is less effective than these agents in reducing triglycerides or increasing HDL-cholesterol concentrations.96,97,101 In several comparative studies in patients with primary hypercholesterolemia or familial combined hyperlipidemia, therapy with lovastatin (20-40 mg daily) reduced total and LDL-cholesterol concentrations by 17-23 and 21-28%, respectively, while total and LDL-cholesterol reductions averaged 6 and 5%, respectively, with niacin; 9 and 2%, respectively, with gemfibrozil; and 13 and 12%, respectively, with fenofibrate.41,96,97 Reductions in triglycerides and increases in HDL-cholesterol concentrations generally were less pronounced among patients treated with lovastatin (8-25% reduction and 6-13% increase) than in those receiving niacin (22% reduction and 18% increase), gemfibrozil (48% reduction and 18% decrease), or fenofibrate (42% reduction and 22% increase).41,96,97

Lovastatin has been used concomitantly with the bile acid sequestrant colestipol8,23,24,36 or cholestyramine90 in a limited number of patients with heterozygous familial hypercholesterolemia or other forms of primary hypercholesterolemia. The addition of a bile acid sequestrant to lovastatin therapy further reduced LDL-cholesterol by 19-26%8,36,90 , resulting in overall LDL-cholesterol reductions of 46-60% in patients receiving lovastatin 40-80 mg daily and either colestipol hydrochloride 10-20 g daily or cholestyramine 4-24 g daily.8,23,24,36,90

Adolescent Patients with Heterozygous Familial Hypercholesterolemia

Lovastatin (immediate-release tablets) is used as an adjunct to dietary therapy to reduce total cholesterol, LDL-cholesterol, and apo B concentrations in the treatment of heterozygous familial hypercholesterolemia in boys and girls (who are at least 1 year postmenarchal) 10-17 years of age who, despite an adequate trial of dietary management, have a LDL-cholesterol concentration >189 mg/dL or a LDL-cholesterol concentration >160 mg/dL and either a family history of premature cardiovascular disease or 2 or more other cardiovascular disease risk factors.118

Efficacy and safety of lovastatin for the treatment of heterozygous familial hypercholesterolemia in adolescent boys were established in a double-blind, placebo-controlled study in boys 10 to 17 years of age.118 Enrolled patients had a baseline LDL-cholesterol level of 189-500 mg/dL and at least one parent with an LDL-cholesterol level >189 mg/dL.118 Mean baseline LDL-cholesterol was 253.1 mg/dL in the lovastatin group and 248.2 mg/dL in the placebo group.118 The dose of lovastatin (administered once daily in the evening as the immediate-release tablet) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter.118 Lovastatin significantly decreased total cholesterol, LDL-cholesterol, and apo B (decreases of 19.3, 24.2, and 21%, respectively) compared to placebo (decreases of 1.1, 1.4, and 4.4%, respectively).118 The mean LDL-cholesterol value achieved was 190.9 mg/dL in the lovastatin group compared to 244.8 mg/dL in the placebo group.118

Efficacy and safety of lovastatin for the treatment of heterozygous familial hypercholesterolemia in adolescent girls were established in a double-blind, placebo-controlled study in girls 10 to 17 years of age who were at least 1 year post-menarche.118 Enrolled girls had a baseline LDL-cholesterol level of 160-400 mg/dL and a parental history of familial hypercholesterolemia.118 Mean baseline LDL-cholesterol was 218.3 mg/dL in the lovastatin group and 198.8 mg/dL in the placebo group.118 The dose of lovastatin (administered once daily in the evening) was 20 mg for the first 4 weeks and 40 mg thereafter.118 Lovastatin significantly decreased total cholesterol, LDL-cholesterol, and apo B (decreases of 22.4, 29.2, and 24.4%, respectively) compared to placebo (increases of 3.6, 2.5, and 6.4%, respectively).118 The mean LDL-cholesterol value achieved was 154.5 mg/dL in the lovastatin group compared to 203.5 mg/dL in the placebo group.118

The safety and efficacy of doses above 40 mg daily have not been studied in children and the long-term efficacy of lovastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.118

Clinical Perspective

Elevated serum cholesterol, especially the LDL-cholesterol fraction, is a major cause of clinical ASCVD; other major risk factors include cigarette smoking, hypertension, diabetes, age, heterozygous familial hypercholesterolemia, chronic kidney disease (eGFR 15-59 mL/minute per 1.73 m2), history of heart failure, and other lipoprotein abnormalities.400,403 Therefore, the goal of antilipemic therapy in patients with hyperlipidemia is to reduce the risk of ASCVD.400 Clinical studies have demonstrated that lovastatin 40-80 mg daily is considered to be a moderate-intensity statin producing approximate LDL-cholesterol reductions of 30-49% when used alone while also reducing the risk of cardiovascular events.118,119,400

The 2018 AHA/ACC cholesterol management guideline emphasizes lifestyle modification as the foundation of ASCVD risk reduction.400 If pharmacologic therapy is needed, statin therapy is recommended as a first-line drug of choice.400

When considering whether to initiate statin therapy for dyslipidemia in the setting of primary prevention, the 2018 AHA/ACC cholesterol management guideline recommends a shared decision-making approach between the patient and clinician.400 The guideline recommends consideration of statin therapy in certain high-risk groups such as adults 20-75 years of age with LDL-cholesterol levels ≥190 mg/dL or higher, 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 of 7.5% or higher.400,401

There is extensive evidence demonstrating that statins can substantially reduce LDL-cholesterol concentrations and associated risk of ASCVD when used for such patients.336,337,338,400,401,402,403 Because the relative risk reduction is correlated with the degree of LDL lowering, the maximum tolerated statin intensity should be used to achieve optimum ASCVD benefits.400,401,402

Combination Antilipemic Therapy

An ACC expert committee update on nonstatin drug therapies recommends that adults without clinical ASCVD with baseline LDL-cholesterol concentrations >190 mg/dL not due to secondary causes may be considered for ezetimibe and/or a PCSK9 mAb inhibitor if they have not met certain thresholds of LDL-cholesterol reduction on maximally tolerated statin therapy for primary prevention (e.g., at least 50% reduction in LDL-cholesterol with an LDL-cholesterol <100 mg/dL or a non-HDL-cholesterol concentration <130 mg/dL).403 Individuals with cholesterol concentrations >190 mg/dL are more likely to have genetic disorders associated with hypercholesterolemia, such as heterozygous familial hypercholesterolemia or homozygous familial hypercholesterolemia.403 Current treatments for patients with heterozygous familial hypercholesterolemia include lifestyle modifications (e.g., low-fat diet, maintenance of a healthy body weight, smoking cessation), first-line treatment with statins, and, if necessary, combination therapy with other lipid-lowering medications (e.g., bile acid sequestrants, ezetimibe, PCSK9 inhibitors, bempedoic acid, inclisiran).403

Hypertriglyceridemia

Patients with moderate or severe hypertriglyceridemia (fasting or non-fasting triglyceride levels 175-499 mg/dL or fasting levels ≥500 mg/dL, respectively) generally are at increased risk of ASCVD and pancreatitis, especially in patients with fasting levels ≥500 mg/dL.400,403 The AHA/ACC cholesterol management guideline recommends assessment and modification of lifestyle (obesity and metabolic syndrome), secondary disorders (e.g., diabetes mellitus, chronic liver or kidney disease and/or nephrotic syndrome, hypothyroidism), and medications that increase triglycerides.400 Initiation or intensification of statin therapy may be considered in adults 40-75 years of age with moderate or severe hypertriglyceridemia and 10-year ASCVD risk of ≥7.5%.400 Experts state statins alone cannot prevent increasing levels of triglycerides in the face of secondary causes from triggering acute hypertriglyceridemic pancreatitis.400

Pediatric Patients

In addition to early identification of children with familial hypercholesterolemia, dietary (e.g., caloric restriction, Mediterranean-style diet) and lifestyle modification (e.g., physical activity) are prioritized for the management of hypercholesterolemia in children and adolescents.400,404 Evidence from randomized controlled trials coupled with the increased risk of cardiovascular disease in untreated severe hypercholesterolemia, support the use of statins in children and adolescents ≥10 years of age with familial hypercholesterolemia.400

In children and adolescents ≥10 years of age with an LDL-cholesterol level persistently ≥190 mg/dL or ≥160 mg/dL with a clinical presentation consistent with familial hypercholesterolemia and who do not respond adequately with 3-6 months of lifestyle therapy, experts state it is reasonable to initiate statin therapy.400 Experts state that statins may be considered as early as 8 years of age in the presence of concerning family history, extremely elevated LDL-cholesterol level, or elevated lipoprotein (a) and in the context of informed shared decision-making and counseling with the patient and family.400,404 Treatment intensity should be based on the severity of the hypercholesterolemia and should incorporate patient/family preference; some experts recommend initiation at the lowest recommended dose and up-titration according to the LDL-cholesterol lowering response and tolerability.400,404 These experts recommend a target LDL-cholesterol level <130 mg/dL or ≥50% reduction from pre-treatment levels, particularly in those with high-risk conditions or other major risk factors; combination therapy with other lipid-lowering medications (e.g., bile acid sequestrants, ezetimibe) may be required.404

Dosage and Administration ⬆ ⬇

[Section Outline]

General !!navigator!!

Pretreatment Screening

Patient Monitoring

Administration !!navigator!!

Oral Administration

Lovastatin is administered orally.118,119 The immediate-release tablets should be administered with the evening meal.118 The extended-release tablets should be administered in the evening at bedtime.119

Store immediate-release tablets at 20-25°C and protect from light.118 Store extended-release tablets at 20-25°C (excursions permitted to 15-30°C); avoid exposure to excessive heat and humidity.119

Dosage !!navigator!!

Reduction in Risk of Cardiovascular Events

Adult Dosage

Immediate-release tablets: The usual recommended starting dosage of lovastatin (as immediate-release tablets) in adults is 20 mg once daily with the evening meal.118 The recommended dosing range is 10-80 mg/day in a single or 2 divided doses; the maximum recommended total daily dose is 80 mg.118

Extended-release tablets: The recommended dosage of lovastatin (as extended-release tablets) in adults ranges from 20 to 60 mg once daily in the evening.119 In geriatric patients (≥65 years of age), the usual initial dosage of lovastatin as extended-release tablets is 20 mg once daily at bedtime.119 Higher dosages should be used only after careful consideration of the potential risks and benefits.119

The AHA/ACC cholesterol management guideline states that the appropriate intensity of statin therapy should be used to reduce ASCVD risk.400 The guideline recommends use of high-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by at least 50%); if high-intensity statin therapy is not possible (e.g., because of a contraindication or intolerable adverse effect), moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30-49%) should be used.400 The AHA/ACC guideline panel considers lovastatin 40-80 mg daily to be a moderate-intensity statin.400

Dyslipidemias

Adult Dosage

Immediate-release tablets: The usual recommended initial dosage of lovastatin (as immediate-release tablets) in adults is 20 mg once daily given with the evening meal.118 The manufacturer states that patients requiring reductions in LDL-cholesterol of 20% or greater should receive an initial lovastatin dosage of 20 mg daily; a dosage of 10 mg daily may be considered for patients requiring smaller reductions in LDL-cholesterol concentration.118 The recommended dosage range of lovastatin as immediate-release tablets in adults is 10-80 mg daily given as a single dose or in 2 divided doses.118 The maximum recommended dosage of lovastatin is 80 mg daily.118 Twice-daily dosing of lovastatin has been used in most clinical studies in patients with heterozygous familial hypercholesterolemia and appears to be slightly but consistently more effective than once-daily dosing;11,15,31,32,40 however, once-daily dosing may be acceptable for patients in whom dosing convenience is considered important for compliance particularly if only moderate degrees of hypercholesterolemia are present.31,60 When given as a single daily dose, lovastatin appears to be more effective when administered in the evening, possibly because cholesterol synthesis occurs mainly at night.15,40,62,118

Extended-release tablets: The recommended dosage of lovastatin (as extended-release tablets) in adults ranges from 20 to 60 mg once daily in the evening.119 In geriatric patients (≥65 years of age), the usual initial dosage of lovastatin as extended-release tablets is 20 mg once daily at bedtime.119 Higher dosages should be used only after careful consideration of the potential risks and benefits.119

Pediatric Dosage

Immediate-release tablets: The recommended dosage range of lovastatin (as immediate-release tablets) for the management of heterozygous familial hypercholesterolemia in children 10-17 years of age is 10-40 mg daily.118 The manufacturer states that patients requiring reductions in LDL-cholesterol of 20% or greater should receive an initial lovastatin dosage of 20 mg daily; a dosage of 10 mg daily may be considered for patients requiring smaller reductions in LDL-cholesterol concentration.118 The maximum recommended dosage of lovastatin in children 10-17 years of age is 40 mg daily.118

Extended-release tablets: Safety and efficacy of lovastatin extended-release tablets have not been established in patients younger than 20 years of age.119

Dosage Modification for Concomitant Therapy

In patients receiving danazol, diltiazem, dronedarone, or verapamil concomitantly with lovastatin, dosage of lovastatin should be initiated at 10 mg daily and should not exceed 20 mg daily.118,119 In patients receiving amiodarone concomitantly with lovastatin, dosage of lovastatin should not exceed 40 mg daily.118,119

Special Populations !!navigator!!

Hepatic Impairment

The manufacturers make no specific dosage recommendations for patients with hepatic impairment.118,119 Lovastatin should be used with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.118,119 Use of lovastatin is contraindicated in patients with active liver disease or unexplained, persistent elevations in serum aminotransferase concentrations.118,119

Renal Impairment

The manufacturer of lovastatin immediate-release tablets states that the drug should be used with caution in patients with severe renal impairment (creatinine clearance <30 mL/minute); dosage increases above 20 mg daily should be carefully considered and, if deemed necessary, implemented cautiously.118 The manufacturer of the extended-release lovastatin preparation states that dosage increases above 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.119

Geriatric Patients

In geriatric patients (≥65 years of age), the usual initial dosage of lovastatin extended-release is 20 mg once daily at bedtime.119 Higher dosages should be used only after careful consideration of the potential risks and benefits.119

Pharmacogenomic Considerations

Patients with solute carrier organic anion transporter (SLCO) 1B1 decreased or possible decreased function phenotypes will have increased lovastatin exposure compared to those with normal function, which may translate to an increased risk of statin-associated musculoskeletal symptoms.500 In such patients, limit lovastatin dosage to ≤20 mg per day; the risk of musculoskeletal symptoms increases with daily dosages greater than 20 mg.500

Patients with SLCO1B1 poor function phenotypes will have increased lovastatin exposure compared to those with normal and decreased function, which may translate to an increased risk of statin-associated musculoskeletal symptoms.500 In such patients, an alternative statin is recommended.500

Cautions ⬆ ⬇

[Section Outline]

Contraindications !!navigator!!

Warnings/Precautions !!navigator!!

Musculoskeletal Effects

Myopathy manifested as muscle pain, tenderness, or weakness with creatine kinase (CK) levels greater than 10 times the upper limit of normal (ULN) and rhabdomyolysis with or without acute renal failure secondary to myoglobinuria have been reported in patients receiving statins, including lovastatin; rare fatalities have occurred.118,119 These adverse effects can occur at any dosage, but the risk is increased in a dose-dependant manner by high levels of HMG-CoA reductase inhibitor activity in the plasma.118,119

Predisposing factors for myopathy include advanced age (≥65 years of age), female gender, and those with renal impairment or uncontrolled hypothyroidism.119 The risk of myopathy/rhabdomyolysis is increased when lovastatin is used concomitantly with other antilipemic agents (niacin or certain fibric-acid derivatives [i.e., gemfibrozil]) or drugs or foods that can increase exposure of lovastatin such as strong inhibitors of CYP3A4 (contraindicated), cyclosporine, danazol, diltiazem, dronedarone, grapefruit juice, verapamil, and amiodarone; some of these drug combinations should be avoided or lovastatin dosage limits may be required.118,119

The AHA/ACC cholesterol management guideline recommends measurement of CK levels in patients with severe statin-associated muscle symptoms; however, routine monitoring is not useful.400 The manufacturer states periodic CK determinations may be considered in patients starting therapy with lovastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.118

Lovastatin should be discontinued if CK concentrations become markedly elevated or if myopathy is diagnosed or suspected.118,119 Lovastatin therapy should be temporarily withheld in any patient experiencing an acute, serious condition suggestive of myopathy or 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).118,119

Immune-Mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has been reported rarely in patients receiving statins.118,119 The condition is 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.118,119 Additional neuromuscular and serologic testing may be necessary.118,119 The risk of IMNM should be considered carefully prior to initiating therapy with another statin, and patients should be monitored for signs and symptoms.118,119

Hepatic Effects

Increases in serum aminotransferase (i.e., AST, ALT) concentrations have been reported in patients receiving statins, including lovastatin.118,119 When the drug was interrupted or discontinued in these patients, transaminase levels usually fell slowly to pretreatment levels.118,119 In early clinical studies, persistent increases exceeding 3 times the ULN in serum aminotransaminase concentrations occurred in 1.9% of adult patients receiving lovastatin for at least 1 year.118,119 The increases usually appeared 3-12 months after the start of therapy with lovastatin and were not associated with jaundice or other clinical signs or symptoms; there was also no evidence of hypersensitivity.118

Liver enzyme tests should be performed prior to initiation of lovastatin therapy and repeated as clinically indicated.118,119 Serious statin-related liver injury is rare and unpredictable in individual patients, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious statin-related liver injury.200 The AHA/ACC cholesterol management guideline states that, during statin therapy, it is reasonable to obtain liver function tests in adults experiencing symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of the skin or sclera); however, routine monitoring is not recommended.200,400

There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including lovastatin.118,119 If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, lovastatin therapy should be promptly interrupted.118,119 If there is no alternate etiology, lovastatin therapy should not be restarted.118,119

Lovastatin should be used with caution in patients who consume substantial amounts of alcohol and/or have a history of chronic liver disease.118,119 The drug is contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.118,119

Hyperglycemic Effects

Increases in glycosylated hemoglobin (hemoglobin A1c [HbA1c]) and fasting serum glucose concentrations have been reported in patients receiving statins, including lovastatin.118,119,200

Data from meta-analyses and clinical trials with other statins indicate that statin therapy may increase the risk of developing diabetes mellitus.200 The AHA/ACC cholesterol management guideline states that patients receiving statin therapy should be evaluated for new-onset diabetes mellitus but because the benefits of statin therapy outweigh the risks of new-onset diabetes, the possibility of this adverse effect should not be a contraindication to statin therapy or a reason for discontinuance of therapy.400

Endogenous Steroid Production

Although clinical studies have shown that lovastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, statins interfere with cholesterol synthesis and theoretically may blunt adrenal or gonadal steroid hormone production.118,119

Clinical studies have shown that lovastatin has no effects on basal plasma cortisol concentrations, testosterone concentrations, or adrenal reserve.118,119 The effects of statins on male fertility or on the pituitary-gonadal axis in premenopausal women are not fully established.118,119

Patients treated with lovastatin who develop clinical evidence of endocrine dysfunction should be evaluated appropriately.118,119 Caution should be exercised if lovastatin is used concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones (e.g., spironolactone, cimetidine).118,119

Specific Populations

Pregnancy

All statins were previously contraindicated in pregnant women because the fetal risk with these drugs was thought to outweigh any possible benefit.405 This determination was based on several factors including safety signals from animal data.405 Lovastatin has produced skeletal malformations in offspring of pregnant mice and rats receiving dosages of 80 mg/kg daily during gestation (7 times the human dose based on body surface area and 5 times the human exposure based on AUC, respectively).14,118 In addition, congenital anomalies including severe CNS defects and unilateral limb deficiencies were reported in a case series of pregnant women who were exposed to a lipophilic statin during the first trimester.400 Because statins decrease synthesis of cholesterol and possibly other products of the cholesterol biosynthetic pathway, there is also a concern that these drugs can potentially cause fetal harm.405 More recent data from case series and observational cohort studies have not shown evidence of an increased risk of major birth defects with statin use during pregnancy, and this was observed after controlling for potential confounders such as maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use.405 The overall evidence from animal studies suggests limited potential for statins to cause malformations or other adverse fetal effects.405 While an increased risk of miscarriage has been reported in pregnant women exposed to statins, it is not clear whether this effect is related to the drugs or to other confounding factors.400,405 FDA conducted a comprehensive review of all available clinical and nonclinical data related to statin use in pregnant women and concluded that the totality of evidence suggests limited potential for statins to cause malformations and other adverse embryofetal effects.405 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.405 While FDA still advises that most pregnant patients discontinue statins because of the possibility of fetal harm, there may be some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) in whom continued therapy may be beneficial; therefore, decisions should be individualized based on the patient's risks versus benefits.400,402,405 Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician who can advise them on the appropriate course of action.405

Lactation

It is not known whether lovastatin is distributed into human milk; however, other statins are distributed into human milk.118,119 Because of the potential for serious adverse reactions from lovastatin in nursing infants, the drug is contraindicated in nursing women; women who require lovastatin therapy should not breast-feed their infants.118,119 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.400,402,405

Females and Males of Reproductive Potential

The effects of statins on male fertility or on the pituitary-gonadal axis in premenopausal women have not been fully established.118,119

Lovastatin may cause fetal harm when administered to a pregnant woman; women (including adolescents) of childbearing age who are treated with statin therapy and are sexually active should be counseled to use a reliable form of contraception.118,119,400

Pediatric Use

Safety and effectiveness of lovastatin immediate-release tablets for the treatment of patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) have been established in controlled clinical trials of 48 weeks' duration in adolescent boys and controlled clinical trials of 24 weeks' duration in girls who were at least 1 year post-menarche.118 The adverse effect profile of lovastatin immediate-release tablets (10-40 mg daily for at least 24 weeks) generally was similar to that of placebo; dosages exceeding 40 mg daily have not been evaluated in this population.118 There were no detectable adverse effects on growth or sexual maturation in adolescent boys or on duration of menstrual cycle in girls.118 If therapy with lovastatin is considered, the manufacturer states that adolescent girls should be advised to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.118 Safety and efficacy of lovastatin have not been evaluated in prepubertal children or in children younger than 10 years of a 118 however, experts state that statins may be considered 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.400,404

Safety and efficacy of lovastatin as extended-release tablets have not been established in children or adolescents younger than 20 years of age.119 Therefore, the manufacturer states that this preparation should not be used in this population.119

Geriatric Use

Results of a pharmacokinetic study in a limited number of patients receiving lovastatin immediate-release tablets (80 mg daily) indicate that mean plasma levels of HMG-CoA reductase inhibitory activity are approximately 45% higher in geriatric patients (70-78 years of age) than in younger adults (18-30 years of age).118,119 However, data from clinical studies and other reported clinical experience employing various preparations of lovastatin suggest that safety and efficacy of the drug in geriatric patients appear to be similar to those in younger adults.118,119 Although dosage adjustment based on age-related pharmacokinetic differences does not appear to be necessary for geriatric patients, greater sensitivity in some older patients cannot be ruled out.119 Because advanced age (65 years of age or older) is a predisposing factor for myopathy, including rhabdomyolysis, the manufacturer states that lovastatin should be prescribed with caution in this population.118 Lower initial dosages of extended-release lovastatin are recommended in geriatric patients.

Because patients older than 75 years of age may have a higher risk of adverse effects and lower adherence to therapy, the expected benefits versus adverse effects should be considered before initiating statin therapy in this population.400

Hepatic Impairment

Lovastatin should be used with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease; use is contraindicated in patients with active liver disease or unexplained, persistent elevations in serum aminotransferase concentrations.118,119 The manufacturers make no specific dosage recommendations.118,119

Renal Impairment

In a study of patients with severe renal impairment (creatinine clearance 10-30 mL/minute), the mean plasma levels of total HMG-CoA reductase inhibitory activity after a single dose of lovastatin were approximately 2-fold higher than those in healthy volunteers.119 In addition to advanced age (≥65 years of age), female gender, and inadequately treated hypothyroidism, renal impairment is another predisposing factor for myopathy.119 Because many patients who have developed rhabdomyolysis during lovastatin therapy have had complicated medical histories, including renal impairment secondary to chronic diabetes mellitus, such patients should be closely monitored.119

The manufacturer states that lovastatin immediate-release tablets should be used with caution in patients with severe renal impairment (creatinine clearance <30 mL/minute); dosage increases above 20 mg daily should be carefully considered and, if deemed necessary, implemented cautiously.118,119 The manufacturer of the extended-release lovastatin preparation states that dosage increases above 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.119

The effect of hemodialysis on plasma levels of lovastatin and its metabolites have not been studied.118,119

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 cytochrome P-450 (CYP) 2C9 genes alter systemic exposure to statins (i.e., lovastatin, simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin), which can increase the risk for statin-associated musculoskeletal symptoms.500 SLCO1B1 encodes a transporter (SLCO1B1; alternative names include organic ion transporter protein [OATP] 1B1 or OATP-C) that facilitates the hepatic uptake of all statins.500 ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin and atorvastatin; CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins (e.g., fluvastatin).500

In patients with phenotypes that result in increased statin exposure, the potential for other patient-specific issues that may increase statin exposure (e.g., renal and hepatic function, drug-drug interactions) must also be considered.500 Experts state that given the balance of statin-associated musculoskeletal symptoms risk versus known cardiovascular disease benefit, for patients who are candidates for new statin therapy, pharmacogenetic test results may provide additional useful information.500

Pharmacogenetic test results may be used as the basis for changing to another statin type or dose for patients currently prescribed statin therapy, depending on how long the patient has been tolerating the statin.500 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, especially if the statin therapy is based on the shared decision making between patient and provider.500

Patients with SLCO1B1 decreased or possible decreased function phenotypes or poor function phenotypes will have increased lovastatin exposure, which may translate to an increased risk of statin-associated musculoskeletal symptoms.500 Patients with such phenotypes may require lower doses or an alternative statin to achieve therapeutic goals without increasing the risk of myopathy.500

There are no data available regarding SLCO1B1 genotype effects on statin response or myopathy in pediatric patients.500

Common Adverse Effects !!navigator!!

Adverse effects reported in at least 2% of patients receiving immediate-release lovastatin include GI disturbances (e.g., flatulence, diarrhea, abdominal pain, constipation, nausea), headache, and myalgia.118

Adverse effects reported in at least 5% of patients receiving extended-release lovastatin include infection, headache, and accidental injury.119

Drug Interactions ⬆ ⬇

[Section Outline]

Lovastatin is metabolized by cytochrome P-450 isoenzyme (CYP) 3A4 but has no CYP3A4 inhibitory activity.118,119 Lovastatin is a substrate of P-glycoprotein (P-gp) and organic anion transporter protein (OATP) 1B1.339,501,502

Drug interaction studies have not been performed with lovastatin extended-release and the types, frequencies, and magnitude of drug interactions that may be encountered may differ from the drug interactions encountered with lovastatin immediate-release.119 The manufacturer of lovastatin extended-release recommends caution when extrapolating lovastatin immediate-release drug interactions and that the monitoring of the pharmacologic effects of the drug and/or other concomitantly administered drugs be undertaken where appropriate.119

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes !!navigator!!

Because lovastatin is metabolized by CYP3A4, strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, cobicistat-containing drugs, grapefruit juice) can increase the risk of myopathy by reducing the elimination of lovastatin.118,119 Concomitant use of lovastatin and strong CYP3A4 inhibitors is therefore contraindicated.118,119 If short-term therapy with a strong CYP3A4 inhibitor is unavoidable, lovastatin therapy must be suspended during the course of treatment.118,119

Lovastatin does not inhibit CYP3A4 and is not expected to alter plasma concentrations of drugs metabolized by CYP3A4.118,119

Drugs Affecting or Affected by Transport Systems !!navigator!!

Lovastatin is a substrate of P-gp and OATP1B1.339,501,502 Concomitant administration of lovastatin with drugs inhibiting P-gp and/or OATP1B1 may increase drug exposure and increase the risk of statin-induced toxicity (e.g., myopathy).502

Other Lipid-lowering Drugs !!navigator!!

The risk of myopathy is increased by other lipid-lowering drugs (e.g., gemfibrozil, other fibrates) that are not strong CYP3A4 inhibitors, but which can also cause myopathy when used alone.118,119,339 Avoid the combined use of gemfibrozil and lovastatin.118,119 Caution should be used if lovastatin is administered with other fibrates or lipid-lowering doses of niacin (≥1 g/day).118,119 Experts state it is safer to use fenofibrate than gemfibrozil because of a lower risk of severe myopathy.400 The benefit of further alterations in lipid levels by the combined use of lovastatin with other fibrates or niacin should be carefully weighed against the potential risks of these combinations.118,119

Amiodarone !!navigator!!

Concomitant use of lovastatin and amiodarone, a CYP3A4 inhibitor, can increase the risk of myopathy and/or rhabdomyolysis.118,119,502 The benefits versus risks of such concomitant therapy should be considered.118,119 If used concomitantly with amiodarone, lovastatin dosage should not exceed 40 mg daily.118,119

Antidiabetic Agents !!navigator!!

No drug interactions have been reported with concomitant use of lovastatin immediate-release tablets with glipizide in pharmacokinetic studies of patients with non-insulin dependent diabetes.118,119

Antifungals, Azoles !!navigator!!

Azole antifungal drugs (e.g., itraconazole, ketoconazole, posaconazole, voriconazole) are strong CYP3A4 inhibitors that can increase the risk of myopathy by reducing the elimination of lovastatin.118,119

Concomitant administration of lovastatin 40 mg and itraconazole 100 or 200 mg daily resulted in a substantial estimated increase in lovastatin AUC of at least 14- and 36-times, respectively.118,119

Concomitant use of lovastatin and itraconazole, ketoconazole, posaconazole, or voriconazole is contraindicated.118,119 If therapy with an azole antifungal is unavoidable, interrupt lovastatin therapy during antifungal treatment.118,119

Calcium-channel Blocking Agents !!navigator!!

Calcium-channel blocking agents (dihydropyridine and nondihydropiridine) are moderate CYP3A4 inhibitors.502 Concomitant use of lovastatin and certain calcium-channel blocking agents (i.e., diltiazem, verapamil) can increase the risk of myopathy and/or rhabdomyolysis.118,119 Concomitant administration of lovastatin 20 mg with diltiazem 120 mg twice daily resulted in a greater than 3-fold increase in lovastatin acid AUC.118,119 The benefits versus risks of such concomitant therapy should be considered.118,119 If used concomitantly with diltiazem or verapamil, the manufacturer recommends initiating lovastatin at 10 mg daily and dosage should not exceed 20 mg daily.118,119 Some experts recommend limiting the lovastatin daily dosage to 20 mg daily if used with concomitant amlodipine.502

Cobicistat-containing Preparations !!navigator!!

Cobicistat is a strong CYP3A4 inhibitor that can increase the risk of myopathy by reducing the elimination of lovastatin.118,119 Concomitant use of lovastatin and cobicistat-containing preparations is contraindicated.118,119

Colchicine !!navigator!!

Cases of myopathy, including rhabdomyolysis, have been reported when lovastatin was used concomitantly with colchicine, a moderate inhibitor of P-gp transport.118,119,502 Use caution with concomitant use of lovastatin and colchicine.118,119

Conivaptan !!navigator!!

Rhabdomyolysis has been reported when lovastatin was used concomitantly with conivaptan.339 Concomitant use of these drugs should be avoided.339

Cyclosporine !!navigator!!

Cyclosporine, a CYP3A4 inhibitor, is also known to inhibit P-gp and the OATP1B1-mediated hepatic uptake of substrates.502 Concomitant use of lovastatin and cyclosporine can increase the risk of myopathy and/or rhabdomyolysis.118 When lovastatin 10 mg daily for 10 days was used concomitantly with cyclosporine in heart or kidney transplant patients (≥9 months post transplant) or patients with psoriasis, lovastatin AUC increased at least 3- to 5-fold. 119 Avoid the combined use of lovastatin with cyclosporine.118,119,118

Danazol !!navigator!!

Concomitant use of lovastatin and danazol can increase the risk of myopathy and/or rhabdomyolysis.118,119 The benefits versus risks of such concomitant therapy should be considered.118,119 If used concomitantly with danazol, the manufacturer recommends initiating lovastatin at 10 mg daily and dosage should not exceed 20 mg daily.118,119

Digoxin !!navigator!!

In patients with hypercholesterolemia, concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations.118,119

Dronedarone !!navigator!!

Concomitant use of lovastatin and dronedarone can increase the risk of myopathy and/or rhabdomyolysis.118,119 The benefits versus risks of such concomitant therapy should be considered.118,119 If used concomitantly with dronedarone, the manufacturer recommends initiating lovastatin at 10 mg daily and dosage should not exceed 20 mg daily.118,119

Fibric Acid Derivatives !!navigator!!

The risk of myopathy is increased by other lipid-lowering drugs (e.g., gemfibrozil, other fibrates) that are not strong CYP3A4 inhibitors, but which can also cause myopathy when used alone.118,119,339 Concomitant administration of lovastatin 40 mg on day 3 of gemfibrozil 600 mg twice daily resulted in a 2.8-fold increase in lovastatin acid AUC.118,119

Avoid the combined use of gemfibrozil and lovastatin; caution should be used if lovastatin is administered with other fibrates.118,119 Experts state it is safer to use fenofibrate than gemfibrozil because of a lower risk of severe myopathy.400 The benefit of further alterations in lipid levels by the combined use of lovastatin with other fibrates should be carefully weighed against the potential risks of these combinations.118,119

Grapefruit Juice !!navigator!!

Administration of lovastatin with grapefruit juice has resulted in substantial increases in plasma concentrations of the antilipemic agent, potentially increasing the risk of myopathy and/or rhabdomyolysis; therefore, the manufacturer and some clinicians recommend that concomitant administration of lovastatin with grapefruit juice should be avoided.118,119,378,379

Concomitant administration of lovastatin 40 mg on day 3 of grapefruit juice consumption (240 mL daily ) resulted in an approximately 2-fold increase in lovastatin AUC.118,119 Concomitant administration of lovastatin 80 mg on day 3 after consumption of a concentrated (i.e., double-strength) grapefruit juice (200 mL 3 times a day for 2 days) resulted in an approximately 15-fold increase in lovastatin AUC.118,119

Because the extent of this interaction may be influenced by the quantity and timing of grapefruit juice consumption, other clinicians suggest that small amounts (e.g., 240 mL) of grapefruit juice may be acceptable; large quantities (>1 quart per day) should be avoided.200,376,378,380

HIV Protease Inhibitors !!navigator!!

Concomitant use of lovastatin and HIV protease inhibitors can increase the risk of myopathy and/or rhabdomyolysis by reducing lovastatin elimination.118,119 Concomitant use of lovastatin and HIV protease inhibitors is contraindicated.118,119

Immunosuppressive Agents !!navigator!!

Concomitant use of lovastatin and cyclosporine can increase the risk of myopathy and/or rhabdomyolysis.118 When lovastatin 10 mg daily for 10 days was used concomitantly with cyclosporine in heart or kidney transplant patients (≥9 months post transplant) or patients with psoriasis, lovastatin AUC increased at least 3- to 5-fold.118,119 Avoid concomitant use of lovastatin with cyclosporine.118,119

Data are more limited with other immunosuppressive agents (i.e., everolimus, sirolimus, tacrolimus), but the drug interaction potential is expected to be similar to cyclosporine because of similar metabolism.339 Some experts recommend avoiding concomitant use of lovastatin with these drugs.339

Macrolides !!navigator!!

Macrolide antibiotics (i.e., clarithromycin, erythromycin) are strong CYP3A4 inhibitors that can increase the risk of myopathy by reducing the elimination of lovastatin.118,119

Concomitant use of lovastatin and erythromycin or clarithromycin is contraindicated.118,119 If therapy with a macrolide antibiotic is unavoidable, interrupt lovastatin therapy during macrolide treatment.118,119

Nefazodone !!navigator!!

Concomitant use of lovastatin and nefazodone can increase the risk of myopathy and/or rhabdomyolysis by reducing lovastatin elimination.118,119 Concomitant use of lovastatin and nefazodone is contraindicated.118,119

Niacin (Antilipemic dosages [1 g/day]) !!navigator!!

Concomitant use of lovastatin and niacin (≥1 g/day) can increase the risk of myopathy and/or rhabdomyolysis.118,119 Caution should be used if lovastatin is administered with niacin (dosage ≥1 g/day).118,119 The benefit of further alterations in lipid levels through the use of lovastatin with niacin should be carefully weighed against the potential risks of the combination.118,119

Propranolol !!navigator!!

No clinically important pharmacokinetic or pharmacodynamic interaction reported in normal volunteers with concomitant administration of lovastatin and propranolol.118,119 The manufacturer of lovastatin extended-release states no dosage adjustment is needed.119

Ranolazine !!navigator!!

Ranolazine is a weak CYP3A4 inhibitor and may also inhibit the efflux transport of P-gp substrates.502 Concomitant use of lovastatin and ranolazine can increase the risk of myopathy and/or rhabdomyolysis.118,119 The manufacturer states lovastatin dosage adjustment may be considered when used concomitantly with ranolazine.118,119

Ticagrelor !!navigator!!

Concomitant use of lovastatin and ticagrelor may result in increased lovastatin exposure.339 Some experts recommend the lovastatin dosage should not exceed 40 mg/day when used concomitantly with ticagrelor.339

Warfarin !!navigator!!

A small clinical trial showed that lovastatin did not potentiate the effect of warfarin (as evidenced by increased prothrombin time [PT]); however, bleeding and/or increased PT or international normalized ratio (INR), have been reported in a few patients taking coumarin anticoagulants with lovastatin.118,119,339

Clinical studies with another statin have shown that concomitant therapy may potentiate the effect of warfarin (as evidenced by increased PT or INR).118,119,339

PT/INR should be monitored when lovastatin is initiated or dosage is adjusted in patients receiving warfarin; thereafter, PT/INR can be monitored at usually recommended intervals.118,119,339

Other Information ⬆ ⬇

Description

Lovastatin is a specific inhibitor of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate (an early and rate-limiting step in cholesterol biosynthesis).118,119,501

Lovastatin is pharmacologically related to other statins (e.g., atorvastatin, fluvastatin, pravastatin, simvastatin, pitavastatin, rosuvastatin).4,5,8,10,17,501

Lovastatin reduces elevated low-density lipoprotein (LDL)-cholesterol concentrations.118,119 The mechanism of the LDL-lowering effect of lovastatin may involve both reduction of very low-density lipoprotein (VLDL) concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-cholesterol.118,119 Triglyceride and apolipoprotein B concentrations may decrease and high-density lipoptotein (HDL)-cholesterol concentration may increase during treatment with lovastatin; however, the effects of such lovastatin-induced changes on coronary heart disease are unknown.118,119,501 Other favorable effects of statins (i.e., pleitropic effects) include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.426,427,501

Lovastatin is a lactone, which is readily hydrolyzed in vivo to β-dihydroxyacid, a strong inhibitor of HMG-CoA reductase.118,119

Lovastatin is lipophilic, undergoes extensive first-pass extraction in the liver, and has low and variable bioavailability; it is estimated that less than 5% of the oral dose reaches the general circulation as active (HMG-CoA) reductase inhibitors.118,119,501 Peak plasma concentrations of both active and total inhibitors were attained within 2-4 hours of dose administration of lovastatin immediate-release tablets.118 The appearance of lovastatin in plasma from the extended-release tablet is slower and more prolonged compared to the immediate-release formulation.119 The properties of lovastatin extended-release are characterized by a prolonged absorptive phase, which results in a longer time to peak (approximately 14 hours) and lower peak concentration for lovastatin and its major metabolite compared to the immediate-release preparation.119

The bioavailability of lovastatin as measured by the 24-hour AUC was greater for the extended-release preparation, compared to lovastatin immediate-release, while the bioavailability of total and active inhibitors of HMG-CoA reductase were equivalent as measured by an enzymatic assay.119 Drug exposure with lovastatin extended-release 60 mg is greater than that with lovastatin immediate-release 80 mg.119

Lovastatin immediate- and extended-release preparations exhibit dose linearity.118,119 Under fasting conditions, plasma concentrations of total inhibitors were on average about two-thirds those found when lovastatin immediate-release was administered immediately after a standard test meal.118 When lovastatin extended-release was administered after a meal, plasma concentrations of lovastatin and lovastatin acid were about 0.5-0.6 times those found when administered in the fasting state, indicating that food decreases the bioavailability of lovastatin extended-release.119 There was also an association between the bioavailability of lovastatin extended-release and dosing at other times.119 Bioavailability was highest under overnight fasting conditions compared to administration before bedtime, or with dinner, or with a high fat breakfast.119

Therapeutic response to lovastatin usually is apparent within 2 weeks and the maximum therapeutic response occurs within 4-6 weeks.118,119 Both lovastatin and its β-hydroxyacid metabolite are highly bound (>95%) to human plasma proteins.118,119 Animal studies demonstrated that lovastatin is distributed mainly to the liver and crosses the blood-brain and placental barriers.118,119 It is not known whether lovastatin is distributed into human milk.118,119 The major active metabolites present in human plasma are the β-hydroxyacid of lovastatin, its 6'-hydroxy derivative, and 2 additional metabolites.118,119,501 Lovastatin is a substrate of cytochrome P-450 (CYP) isoenzyme 3A4, P-glycoprotein (P-gp), and organic anion transporter protein (OATP) 1B1.118,119,339,501,502 In humans, lovastatin was excreted 10% in the urine and 83% in the feces following an oral dose of radiolabeled immediate-release lovastatin.118,119

Advice to Patients

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.

Lovastatin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Lovastatin Tablets

20 mg*

Lovastatin Tablets

40 mg*

Lovastatin Tablets

Tablets, extended-release

20 mg

Altoprev®

Covis

40 mg

Altoprev®

Covis

60 mg

Altoprev®

Covis

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

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions July 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

Only references cited for selected revisions after 1984 are available electronically.

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5. Tobert JA, Bell GD, Birtwell J et al. Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in healthy volunteers. J Clin Invest . 1982; 69:913-9. [PubMed 6918402]

6. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: a new class of cholesterol-lowering agents. Ann Intern Med . 1987; 107:759-60. Editorial.

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14. Minsker DH, MacDonald JS, Robertson RT et al. Mevalonate supplementation in pregnant rats suppresses the teratogenicity of mevinolinic acid, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Teratology . 1983; 28:449-56. [PubMed 6665743]

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16. Cressman MD, Hoogwerf BJ, Moodie DS et al. HMG-CoA reductase inhibitors: a new approach to the management of hypercholesterolemia. Cleveland Clin J Med . 1988; 55:93-100.

17. Rosen T, Heathcock CH. The synthesis of mevinic acids. Tetrahedron . 1986; 42:4909-51.

18. The Lovastatin Study Group III. A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia. JAMA . 1988; 260:359-66. [PubMed 2898027]

19. East C, Bilheimer DW, Grundy SM. Combination drug therapy for familial combined hyperlipidemia. Ann Intern Med . 1988; 109:25-32. [PubMed 3288029]

22. Fojo SS, Hoegg JM [sic: Hoeg], Lackner KJ et al. Adrenocortical function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin). Horm Metab Res . 1987; 19:648-52. [PubMed 2831127]

23. Grundy SM, Vega GL, Bilheimer DW. Influence of combined therapy with mevinolin and interruption of bile-acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia. Ann Intern Med . 1985; 103:339-43. [PubMed 3849281]

24. Bilheimer DW, Grundy SM, Brown MS et al. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci USA . 1983; 80:4124-8. [PubMed 6575399]

25. Davignon J, Dujovne CA, Frohlich J et al. A comparison of lovastatin and probucol for the treatment of primary hypercholesterolemia. Unpublished observations. 1988 Jul.

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