Brand name: Altoprev
Drug class: HMG-CoA Reductase Inhibitors
- Statins
VA class: CV350
Chemical name: 2-Methylbutanoic acid [1S-[1α(R*),3α,7β,8β(2S*,4S*),8aβ]-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester
Molecular formula: C₂₄H₃₆O₅
CAS number: 75330-75-5

Medically reviewed by Drugs.com on Dec 22, 2023. 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 prevention or primary prevention in high-risk patients.

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

Because relative ASCVD risk reduction is correlated with degree of LDL-cholesterol lowering, use maximum tolerated intensity of a statin to achieve greatest benefit. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is recommended; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%). AHA/ACC considers 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 hypercholesterolemia and other causes of hypercholesterolemia (e.g., polygenic hypercholesterolemia). Also used in combination with fenofibrate to decrease triglyceride concentrations and increase HDL-cholesterol concentrations in patients with mixed dyslipidemia and CHD (or CHD risk equivalents) who are on optimal statin therapy; however, no incremental benefit on cardiovascular morbidity and mortality beyond that provided by statin monotherapy.

Adjunct to 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.

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, VLDLs, or IDLs.

Reduction of total and LDL-cholesterol concentrations in patients with familial dysbetalipoproteinemia or with hypercholesterolemia associated with or exacerbated by diabetes mellitus^{† [off-label]} (diabetic dyslipidemia), cardiac^{† [off-label]} or renal transplantation^{† [off-label]}, nephrotic syndrome^{† [off-label]} (nephrotic hyperlipidemia), or distal ileal bypass surgery^{† [off-label]}.

Reduction of total cholesterol, LDL cholesterol, and/or apolipoprotein B in patients with hypoalphalipoproteinemia^† or in those with mild endogenous (primary) hypertriglyceridemia and borderline elevated total cholesterol, decreased HDL cholesterol, and elevated apo B^† (type IV hyperlipoproteinemia with elevated total apo B).

Lovastatin Dosage and Administration

General

Patient Monitoring

Antilipemic Therapy

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

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

Administration

Oral Administration

Manufacturer and some clinicians recommend that patients avoid grapefruit juice. (See Specific Drugs and Foods under Interactions.) Because extent of the interaction may be influenced by quantity and timing of grapefruit juice consumption, other clinicians suggest that small amounts (e.g., 240 mL) may be acceptable.

Conventional Tablets

Administer orally with the evening meal.

Extended-release Tablets

Administer orally in the evening at bedtime.

Dosage

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

Pediatric Patients

Dyslipidemias

Conventional 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.

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed. Recommended dosage range is 10–40 mg daily.

Adults

Reduction in Risk of Cardiovascular Events

Oral

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

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

Dyslipidemias

Conventional Tablets

Oral

Usual initial dosage is 20 mg once daily.

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.

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed. Recommended dosage range is 10–80 mg daily given in 1 or 2 divided doses.

Extended-release Tablets

Oral

Recommended dosage range is 20–60 mg once daily. Adjust dosage at intervals of ≥4 weeks until desired effect on lipoprotein concentrations is observed.

Prescribing Limits

Pediatric Patients

Dyslipidemias

Conventional Tablets

Oral

Children 10–17 years of age: Maximum 40 mg daily.

Adults

Prevention of Cardiovascular Events or Management of Dyslipidemias

Conventional Tablets

Oral

Maximum 80 mg daily.

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.

Renal Impairment

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. (See Musculoskeletal Effects under Cautions.)

Geriatric Patients

Conventional 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. (See Musculoskeletal Effects under Cautions.)

Cautions for Lovastatin

Contraindications

• Concomitant use with potent CYP3A4 inhibitors (e.g., clarithromycin, cobicistat-containing preparations, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole). (See Specific Drugs and Foods under Interactions.)

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

• Lactation.

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

Warnings/Precautions

Musculoskeletal Effects

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

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in S_cr [usually accompanied by brown urine and urinary myoglobinuria]) with or without acute renal failure secondary to myoglobinuria has been reported; rare fatalities have occurred.

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

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

Certain drug or food interactions also may increase risk of myopathy and/or rhabdomyolysis. (See Contraindications under Cautions and also see Interactions.)

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.

Temporarily withhold therapy in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).

Hepatic Effects

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

Pancreatitis, hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty change in liver, increased serum alkaline phosphatase concentrations, increased serum γ-glutamyl transpeptidase concentrations, increased bilirubin concentrations, cirrhosis, fulminant hepatic necrosis, hepatoma, and fatal and nonfatal hepatic failure have been reported.

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

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.

Also see Hepatic Impairment under Cautions.

Hyperglycemic Effects

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

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

Endogenous Steroid Production

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

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).

Cognitive Impairment

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

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

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

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

If patients present with confusion or memory impairment, ACC/AHA cholesterol management guideline recommends evaluating patient for statin as well as nonstatin causes (e.g., other drugs, systemic or neuropsychiatric causes).

Role as Adjunct Therapy

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

Specific Populations

Pregnancy

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

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

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

Lactation

Not known whether lovastatin is distributed into 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.

Pediatric Use

Safety and efficacy of conventional tablets not established in children <10 years of age or in prepubertal children. 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.

Conventional 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. (See Geriatric Patients under Dosage and Administration.)

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

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. (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

GI disturbances (e.g., flatulence, diarrhea, abdominal pain, constipation, nausea, dyspepsia), headache, myalgia, asthenia, blurred vision, rash, dizziness, muscle cramps, insomnia.

Drug Interactions

Metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma lovastatin concentrations); increased risk of myopathy or rhabdomyolysis. Concomitant use contraindicated. (See Contraindications under Cautions.)

Specific Drugs and Foods

Lovastatin Pharmacokinetics

Absorption

Bioavailability

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

Conventional 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 conventional tablets.

Extended-release tablets: More bioavailable (in terms of lovastatin) than conventional tablets; however, bioavailability of total and active HMG-CoA reductase inhibitors is similar between the 2 formulations.

Food

Overall bioavailability is decreased by approximately 50% when given 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%).

Half-life

0.5–3 hours.

Special Populations

Plasma concentrations of total inhibitors increased twofold in patients with severe renal impairment (Cl_cr 10–30 mL/min) compared with healthy individuals following a single dose. (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Conventional Tablets

Well-closed, light-resistant containers at 5–25°C; protect from light.

Extended-release Tablets

20–25°C (may be exposed 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.

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

Advice to Patients

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

• Risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages (i.e., 80 mg daily) or when used concomitantly with certain drugs or grapefruit juice. Importance of patients promptly reporting muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, or if manifestations persist after discontinuance of therapy.

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

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

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

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

• Importance of avoiding breast-feeding during therapy. If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.

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

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

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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