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Lovastatin

Pronunciation

Class: HMG-CoA Reductase Inhibitors
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
Brands: Altoprev

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).1 2 3 4 5 118 119

Uses for Lovastatin

Prevention of Cardiovascular Events

ACC/AHA cholesterol management guideline recommends statins as first-line therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in adults; extensive evidence demonstrates that statins can substantially reduce ASCVD risk when used for secondary prevention or primary prevention (in high-risk patients).336 337 338 350 Relative reduction in ASCVD risk is correlated with degree of LDL-cholesterol lowering; therefore, use maximum tolerated statin intensity to achieve optimum ASCVD benefits.350 According to ACC/AHA, lovastatin may be used for primary or secondary prevention in adults when moderate-intensity statin therapy is indicated.350 (See Prevention of Cardiovascular Events under Dosage and Administration.)

Adjunct to nondrug therapies (i.e., 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.1 83 118 119 350 Consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy for primary prevention.350

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.1 61 70 74 75 76 91 92 93 118 119

Current recommendations from ACC/AHA regarding prevention of ASCVD and lifestyle modifications to reduce cardiovascular risk are available at or 352

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).1 2 8 9 18 23 24 29 30 31 32 33 35 36 40 44 49 50 90 118 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.353

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.1 118

Reduction of elevated LDL-cholesterol concentrations in patients with combined hypercholesterolemia and hypertriglyceridemia caused by genotypic familial combined hyperlipidemia,1 2 18 19 31 44 50 118 however, has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDLs, or IDLs.1 18

Reduction of total and LDL-cholesterol concentrations in patients with familial dysbetalipoproteinemia34 50 104 or with hypercholesterolemia associated with or exacerbated by diabetes mellitus (diabetic dyslipidemia),50 52 cardiac50 53 54 102 or renal transplantation,50 54 103 nephrotic syndrome (nephrotic hyperlipidemia),27 50 55 or distal ileal bypass surgery.23 33 56

Reduction of total cholesterol, LDL-cholesterol, and/or apolipoprotein B in patients with hypoalphalipoproteinemia98 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).42 43

Lovastatin Dosage and Administration

General

  • Patients should be placed on a standard lipid-lowering diet before initiation of lovastatin therapy and should remain on this diet during treatment with the drug.1 118 119

Monitoring during Antilipemic Therapy

  • ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350

  • Periodically reinforce adherence to lifestyle modifications.350

Administration

Oral Administration

Manufacturer and some clinicians recommend that patients avoid grapefruit juice.64 118 119 379 (See Specific Drugs and Foods under Interactions.) Because extent of the interaction may be influenced by quantity and timing of grapefruit juice consumption,118 other clinicians suggest that small amounts (e.g., 240 mL) may be acceptable.376 378

Conventional Tablets

Administer orally with the evening meal.118

Extended-release Tablets

Administer orally in the evening at bedtime.119

Dosage

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.1 118

Children 10–17 years of age who require small reductions in LDL-cholesterol: Consider initial dosage of 10 mg once daily.1 118

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.1 Recommended dosage range is 10–40 mg daily.1 118

Adults

Prevention of Cardiovascular Events

Select appropriate statin intensity to achieve optimal ASCVD risk reduction.350 Giving maximally tolerated statin intensity is preferred over giving lower statin dosages in combination with nonstatin drugs, a strategy not yet shown to reduce ASCVD risk.350

Primary Prevention in Patients with LDL-cholesterol Concentrations ≥190 mg/dL (≥21 years of age)
Oral

ACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

Primary Prevention in Patients with Type 1 or 2 Diabetes Mellitus (40–75 years of age)
Oral

ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., lovastatin 40 mg once daily).350

If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients <40 or >75 years of age, consider potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.350

Primary Prevention in Patients with LDL-cholesterol Concentrations 70–189 mg/dL and Elevated ASCVD Risk (40–75 years of age)
Oral

Estimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- (e.g., lovastatin 40 mg once daily) to high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin).350

Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline states may consider moderate-intensity statin therapy.350

Consider potential benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

Secondary Prevention in Patients with Clinical ASCVD (i.e., acute coronary syndromes; history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) (21–75 years of age)
Oral

ACC/AHA cholesterol management guideline recommends high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., lovastatin 40 mg once daily) if tolerated.350

Patients >75 years of age: Individualize therapy based on potential benefits, adverse effects, drug interactions, and patient preferences; may consider moderate-intensity statin therapy if tolerated.350

Dyslipidemias
Conventional Tablets
Oral

Usual initial dosage is 20 mg once daily.118

Patients who require reductions in LDL-cholesterol concentrations of ≥20%: Initially, 20 mg once daily.1 118

Patients who require smaller reductions in LDL-cholesterol: Consider initial dosage of 10 mg once daily.1 118

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.1 Recommended dosage range is 10–80 mg daily given in 1 or 2 divided doses.1 118

Extended-release Tablets
Oral

Recommended dosage range is 20–60 mg once daily.119 Adjust dosage at intervals of ≥4 weeks until desired effect on lipoprotein concentrations is observed.1

Dosage Modification
Oral

ACC/AHA cholesterol management guideline states may consider decreasing statin dosage when LDL-cholesterol concentrations are <40 mg/dL on 2 consecutive measurements; however, no data to suggest that LDL-cholesterol concentrations <40 mg/dL increase risk of adverse effects.350

Prescribing Limits

Pediatric Patients

Dyslipidemias
Conventional Tablets
Oral

Children 10–17 years of age: Maximum 40 mg daily.1 118

Adults

Prevention of Cardiovascular Events or Management of Dyslipidemias
Conventional Tablets
Oral

Maximum 80 mg daily.1

Special Populations

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.1 118

Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.1 118

Renal Impairment

Use with caution in patients with severe renal impairment (Clcr <30 mL/min).1 Carefully consider dosage increases >20 mg daily in such patients; if deemed necessary, implement with extreme caution.1

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.119 (See Musculoskeletal Effects under Cautions.)

Geriatric Patients

Conventional Tablets

Dosage adjustment based on age-related pharmacokinetic differences not necessary.118

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.119 (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).118 119 (See Specific Drugs and Foods under Interactions.)

  • Active liver disease or unexplained, persistent elevations of serum aminotransferases.1 118

  • Pregnancy or lactation.1 Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.1 118

  • Known hypersensitivity to lovastatin or any ingredient in the formulation.1 118

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

Suppression of cholesterol biosynthesis could cause fetal harm.1 118 Skeletal malformations reported in animal reproductive studies.118 Congenital anomalies following intrauterine exposure to statins reported rarely.1 118

Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.1 118 If the patient becomes pregnant while taking the drug, immediately discontinue therapy and apprise the patient of the potential hazard to the fetus.1 118

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.1 118

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in Scr [usually accompanied by brown urine and urinary myoglobinuria])437 with or without acute renal failure secondary to myoglobinuria has been reported;1 118 rare fatalities have occurred.1

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins.118 119 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.118 119

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.118 119

Certain drug or food interactions also may increase risk of myopathy and/or rhabdomyolysis.1 118 119 (See Contraindications under Cautions and also see Interactions.)

May consider periodic monitoring of CK concentrations when initiating therapy or increasing dosage; however, there is no assurance that such monitoring will prevent myopathy.118

ACC/AHA cholesterol management guideline does not recommend routine monitoring of CK concentrations in adults; however, may obtain CK concentrations before initiating therapy in adults at increased risk of developing adverse musculoskeletal effects (e.g., patients with personal or family history of statin intolerance or muscle disease, patients receiving concomitant therapy with myotoxic drugs).350 During statin therapy, may measure CK concentrations in adults with muscle symptoms (e.g., pain, tenderness, stiffness, cramping, weakness, generalized fatigue).350

National Heart, Lung, and Blood Institute (NHLBI) expert panel on integrated guidelines cardiovascular health and risk reduction in children and adolescents recommends obtaining CK concentrations before initiating statin therapy and routinely monitoring for muscle toxicity during therapy.357

Discontinue if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected.1 118 119

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).1 118 119

Hepatic Effects

Associated with increases in serum aminotransferase (AST, ALT) concentrations.1 118 119

Pancreatitis,1 118 hepatitis (including chronic active hepatitis),1 118 cholestatic jaundice,1 118 fatty change in liver,1 118 increased serum alkaline phosphatase concentrations,1 118 increased serum γ-glutamyl transpeptidase concentrations,1 118 increased bilirubin concentrations,1 118 cirrhosis,1 118 fulminant hepatic necrosis,1 118 hepatoma,1 118 and fatal and nonfatal hepatic failure118 119 have been reported.1 118 119

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage201 ).118 119 Although manufacturers previously recommended more frequent monitoring,1 FDA concluded that serious statin-related liver injury is rare and unpredictable, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.200 ACC/AHA cholesterol management guideline recommends obtaining liver function tests in adults with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera).350 However, NHLBI expert panel on cardiovascular health and risk reduction in children and adolescents strongly recommends routine monitoring of hepatic function in children and adolescents receiving statins.357

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt lovastatin therapy.118 119 If an alternate etiology is not found, do not restart lovastatin.118 119

Also see Hepatic Impairment under Cautions.

Hyperglycemic Effects

Increases in HbA1c and fasting serum glucose concentrations reported.118 119 200 Possible increased risk of developing diabetes.200 May need to monitor glucose concentrations following initiation of statin therapy.201

FDA states that cardiovascular benefits of statins outweigh these small increased risks.200

ACC/AHA cholesterol management guideline recommends evaluating patients for new-onset diabetes mellitus according to current diabetes screening guidelines.350

If diabetes mellitus develops during statin therapy, encourage patients to adhere to a heart-healthy diet, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce the risk of ASCVD.350

Endogenous Steroid Production

Statins interfere with cholesterol synthesis and theoretically may blunt adrenal and/or gonadal steroid production.118 119

No effects on basal plasma cortisol concentrations, testosterone concentrations, or adrenal reserve observed with lovastatin.118 119 Effects on male fertility or on pituitary-gonadal axis in premenopausal women not fully established.118 119

If clinical evidence of endocrine dysfunction is present, evaluate patients appropriately.118 119

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).118 119

Cognitive Impairment

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) reported rarely.118 119

Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy).118 119 200 Not associated with fixed or progressive dementia (e.g., Alzheimer’s disease) or clinically important cognitive decline.200 Not associated with any specific statin, patient's age, statin dosage, or concomitant drug therapy.200

FDA states that cardiovascular benefits of statins outweigh the small increased risk of cognitive impairment.200

If manifestations consistent with cognitive impairment occur, National Lipid Association (NLA) statin safety assessment task force recommends evaluating and managing patients appropriately.202

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).350

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.1 118

Specific Populations

Pregnancy

Category X.1 118 Safety in pregnant women not established.118 119 Discontinue immediately if pregnancy is known or suspected.118 119 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Not known whether lovastatin is distributed into milk; however, other statins are distributed into milk.118 119 Use is contraindicated in nursing women; women who require lovastatin therapy should not breast-feed their infants.1 118 119

Pediatric Use

Safety and efficacy of conventional tablets not established in children <10 years of age or in prepubertal children.1 Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.1

Safety and efficacy of extended-release lovastatin not established in children or adolescents <20 years of age.119

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.1 118

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.118 Because advanced age (≥65 years of age) is a predisposing factor for myopathy, including rhabdomyolysis, use with caution in this population.118

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

Use with caution.119 437 In patients >75 years of age, consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.1 118

Contraindicated in patients with active liver disease or unexplained, persistent increases in liver function test results.1 118

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.118 (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.1 118 119

Interactions for Lovastatin

Metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.1 118

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma lovastatin concentrations); increased risk of myopathy or rhabdomyolysis.118 119 Concomitant use contraindicated.118 119 (See Contraindications under Cautions.)

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Amiodarone

Increased risk of myopathy and/or rhabdomyolysis1 339

If used concomitantly, do not exceed lovastatin dosage of 40 mg daily; avoid concomitant use of lovastatin dosages >40 mg daily unless clinical benefit likely to outweigh increased risk of myopathy1 118 119 339

Antidiabetic agents (e.g., chlorpropamide, glipizide)

Chlorpropamide or glipizide: Pharmacokinetic interactions not reported during concomitant use118 119

Antifungals, azoles

Itraconazole, ketoconazole, posaconazole, or voriconazole: Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and AUC and increased risk of myopathy and/or rhabdomyolysis1 118 119

Itraconazole, ketoconazole, posaconazole, or voriconazole: Concomitant use contraindicated; if therapy with antifungal is unavoidable, interrupt lovastatin therapy during antifungal treatment118 119

Calcium-channel blockers (i.e., amlodipine, diltiazem, verapamil)

Increased plasma lovastatin concentrations and possible risk of myopathy and/or rhabdomyolysis, particularly with higher lovastatin dosages1 118 119 339

Weigh benefits versus risks of concomitant use118 119 339

If used concomitantly with diltiazem or verapamil, manufacturer recommends initiating lovastatin at 10 mg daily118 119

Lovastatin dosage >20 mg daily not recommended when coadministered with any of these calcium-channel blockers118 119 339

Cobicistat-containing preparations

Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased plasma concentrations and AUC of lovastatin and increased risk of myopathy and/or rhabdomyolysis118 119

Concomitant use contraindicated118 119

Colchicine

Myopathy, including rhabdomyolysis, reported118 119 339

Use concomitantly with caution118 119

Conivaptan

Rhabdomyolysis reported 339

Avoid concomitant use339

Danazol

Increased risk of myopathy and/or rhabdomyolysis, particularly with higher lovastatin dosages118 119

Weigh benefits against risks of concomitant use118 119

If used concomitantly, initiate lovastatin at 10 mg daily118 and do not exceed lovastatin dosage of 20 mg daily118 119

Digoxin

No effect on digoxin plasma concentrations118 119

Dronedarone

Inhibition of lovastatin metabolism via CYP3A4, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis, particularly with higher lovastatin dosages118 339

Weigh benefits against risks of concomitant use118

If used concomitantly, initiate lovastatin at 10 mg daily and do not exceed lovastatin dosage of 20 mg daily118

Fibric acid derivatives (e.g., gemfibrozil)

Increased risk of myopathy and/or rhabdomyolysis1

Gemfibrozil: Increased AUC of lovastatin acid118 119

Gemfibrozil: Avoid concomitant use118 119

Other fibric acid derivatives (e.g., fenofibrate): Use concomitantly with caution and only if benefits outweigh risks; consider using only low- or moderate-intensity statin therapy during concomitant therapy118 119 350

Grapefruit juice

Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin AUC and plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 118 119

Manufacturer and some clinicians recommend avoiding concomitant use118 119 379

HIV protease inhibitors

Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 118 119

Concomitant use contraindicated118 119

Immunosuppressive agents (i.e., cyclosporine, everolimus, sirolimus, tacrolimus)

Cyclosporine: Increased lovastatin AUC and increased risk of myopathy and/or rhabdomyolysis1 118 119 339

Everolimus, sirolimus, tacrolimus: Data more limited, but interaction potential expected to be similar to cyclosporine because of similar metabolism339

Cyclosporine: Avoid concomitant use 118 119 339

Everolimus, sirolimus, tacrolimus: Some experts recommend avoiding concomitant use339

Lomitapide

Possible increased exposure to lovastatin374

Consider reducing lovastatin dosage when initiating lomitapide374

Macrolides (i.e., clarithromycin, erythromycin)

Clarithromycin or erythromycin: Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 118 119

Clarithromycin or erythromycin: Concomitant use contraindicated; if therapy with antibiotic is unavoidable, interrupt lovastatin therapy during antibiotic treatment118 119

Nefazodone

Inhibition of lovastatin metabolism via CYP3A4, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 118 119

Concomitant use contraindicated118 119

Niacin (antilipemic dosages [≥1 g daily])

Increased risk of myopathy and/or rhabdomyolysis1 118 119

Increased risk of severe adverse effects (disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, bleeding) with concomitant use of niacin (1.5–2 g daily) and simvastatin (40–80 mg daily, with or without ezetimibe)369 371

Use concomitantly with caution; weigh benefits against risks of concomitant use118 119

Propranolol

No clinically important pharmacokinetic or pharmacodynamic interaction reported118 119

Dosage adjustment not needed.119

Ranolazine

Possible increased risk of myopathy, including rhabdomyolysis118 119

If used concomitantly, may consider adjusting lovastatin dosage118 119 339

Telithromycin

Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis118 119

Concomitant use contraindicated; if therapy with telithromycin is unavoidable, interrupt lovastatin therapy during telithromycin treatment118 119

Ticagrelor

Possible increased lovastatin plasma concentrations339

Some experts recommend limiting lovastatin dosage to 40 mg daily339

Warfarin

Bleeding and/or increased PT observed1 118 339

Closely monitor PT until stabilized if lovastatin is initiated or dosage is adjusted in patients receiving warfarin;1 118 339 thereafter, monitor PT at intervals usually recommended for patients receiving warfarin1 118

Lovastatin Pharmacokinetics

Absorption

Bioavailability

Conventional tablets: Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver.1 429 430 431 432 Peak plasma concentrations attained at 2–4 hours.1

Conventional tablets: Absolute bioavailability is <5%.1 430

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.119

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.119

Food

Overall bioavailability is decreased by approximately 50% when given without food.339

Onset

Therapeutic response usually is apparent within 2 weeks; maximal response occurs within 4–6 weeks.1

Distribution

Extent

Distributed mainly to the liver; crosses the blood-brain barrier.1

Lovastatin crosses the placenta.1 Not known whether distributed into human milk.1 118

Plasma Protein Binding

>95%.1

Elimination

Metabolism

Metabolized by CYP3A4.1 Lovastatin has active metabolites.1

Elimination Route

Excreted in urine (10%) and feces (83%).1

Half-life

0.5–3 hours.429 431 432

Special Populations

Plasma concentrations of total inhibitors increased twofold in patients with severe renal impairment (Clcr 10–30 mL/min) compared with healthy individuals following a single dose.1 118 (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Conventional Tablets

Well-closed, light-resistant containers at 5–25°C; protect from light.118

Extended-release Tablets

20–25°C (may be exposed to 15–30°C).119 Avoid excessive heat and humidity.119

Actions

  • Prodrug requiring hydrolysis in vivo for activity.1 118

  • Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.1 18 Reduces serum concentrations of total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglycerides.1 118

  • Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries,70 74 75 91 118 413 414 415 416 417 418 423 modulate blood pressure in hypercholesterolemic patients with hypertension,424 425 and possess anti-inflammatory activity.426 427

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.118 119 350

  • 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.118 119 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.118 119

  • Risk of adverse hepatic effects.118 119 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).118 119

  • Risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).118 119 200

  • Risk of increased glucose concentrations and development of type 2 diabetes.118 119 200 May need to monitor glucose concentrations following initiation of statin therapy.201

  • Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) during therapy and informing pregnant women of risk to fetus.118 119

  • Importance of avoiding breast-feeding during therapy.118 119 If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.119

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.118 119 (See Cautions.)

Preparations

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

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

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

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

AHFS DI Essentials. © Copyright 2017, Selected Revisions June 26, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

1. Merck. Mevacor (lovastatin tablets) prescribing information. Whitehouse Station, NJ; 2002 Jun.

2. Merck Sharp & Dohme. Mevacor formulary information. West Point, PA; 1987.

3. United States Pharmacopeial Convention, Inc. USAN and the USP dictionary of drug names. Rockville, MD: United States Pharmacopeial Convention, Inc.; 1988: 311-2.

4. Tobert JA, Hitzenberger G, Kukovetz WR et al. Rapid and substantial lowering of human serum cholesterol by mevinolin (MK-803), an inhibitor of hydroxymethylglutaryl-coenzyme A reductase. Atherosclerosis. 1982; 41:61-5. [PubMed 6918220]

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