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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: Advicor, Altoprev, Mevacor

Introduction

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

Uses for Lovastatin

Prevention of Cardiovascular Events

Adjunct to nondrug therapies (e.g., dietary management) 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.1 116 118 119

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.1 116 118 119

May use in fixed combination with extended-release niacin when treatment with both lovastatin (for prevention of cardiovascular events) and extended-release niacin (for dyslipidemias and/or prevention of cardiovascular events) is appropriate.120

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 90 116 118

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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 however, has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDLs, or IDLs.1

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

May use in fixed combination with extended-release niacin when treatment with both lovastatin (for dyslipidemias) and extended-release niacin (for dyslipidemias and/or prevention of cardiovascular events) is appropriate.120

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.1 116 117

Monitoring during Antilipemic Therapy

  • Monitor lipoprotein concentrations periodically to ensure that target LDL-cholesterol goals are achieved and maintained at <100 mg/dL (optional goal: <70 mg/dL) for patients with CHD or CHD risk equivalents; <130 mg/dL (optional goal: <100 mg/dL) for patients with ≥2 risk factors and 10-year risk of 10–20%; <130 mg/dL for patients with ≥2 risk factors and 10-year risk <10%; or <160 mg/dL for patients with 0–1 risk factor.

Administration

Oral Administration

Conventional Tablets

Administer orally with the evening meal.1

Extended-release Tablets

Administer orally at bedtime.116

Swallow tablets whole; do not cut, crush or chew.116 119

Lovastatin/Extended-release Niacin Fixed-combination Tablets (Advicor)

Administer orally at bedtime with a low-fat snack.117

Swallow tablets whole; do not break, crush, or chew.117

Increase dosage slowly to minimize symptoms of flushing, pruritus, and GI distress associated with the niacin component; avoid administration on an empty stomach.117 Pretreatment with aspirin up to the recommended dose of 325 mg (administered up to approximately 30 minutes prior to administration of Advicor) may reduce flushing.117 120

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 or Management of 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

Initially, 20, 40, or 60 mg once daily.116 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

In patients with complicated medical conditions (e.g., diabetes), usual initial dosage is 20 mg once daily; use higher dosages only after careful consideration of potential risks and benefits.119 (See Musculoskeletal Effects under Cautions.)

Extended-release lovastatin not recommended in patients requiring smaller reductions in cholesterol concentrations; may consider immediate-release lovastatin.119

Lovastatin/Extended-release Niacin Fixed-combination Tablets (Advicor)
Oral

Patients not currently receiving extended-release niacin (as Niaspan): Must start therapy with the fixed combination (Advicor) at the lowest available dosage (lovastatin 20 mg and extended-release niacin 500 mg as a single tablet once daily).120 Increase dosage by no more than 500 mg daily (of niacin component) at 4-week intervals.120 Adjust dosage according to individual requirements (i.e., target cholesterol and triglyceride goals) and response.120 Dosages >40 mg of lovastatin and 2 g of extended-release niacin daily not recommended.120 If fixed-combination therapy has been discontinued for >7 days, reinstitute at the lowest available dosage.120

Advicor may be substituted for equivalent dosages of Niaspan only; do not substitute for other modified- or immediate-release niacin preparations.120

Patients already receiving a stable dosage of Niaspan: May switch directly to a niacin-equivalent dosage of Advicor.120

Patients receiving niacin preparations other than Niaspan: Switch from existing niacin therapy to Niaspan at the recommended dosage titration schedule, then adjust niacin dosage according to individual response before switching to Advicor.117 120

Because of differences in bioavailability, do not substitute 1 tablet of Advicor 1 g/40 mg for 2 tablets of Advicor 500 mg/20 mg, or vice versa.117

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

Lovastatin/Extended-release Niacin Fixed-combination Tablets (Advicor)
Oral

Maximum 40 mg of lovastatin and 2 g of extended-release niacin daily.117

Special Populations

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.1 116 117

Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.1 116 117

Renal Impairment

Use with caution in patients with severe renal impairment (Clcr <30 mL/min).1 116 Carefully consider dosage increases >20 mg daily; if deemed necessary, implement with extreme caution.1 116

Extended-release Tablets

Usual initial dosage is 20 mg once daily; use higher dosages only after careful consideration of potential risks and benefits.119 (See Musculoskeletal Effects under Cautions.)

Extended-release tablets not recommended in patients requiring smaller reductions in cholesterol concentrations; may consider immediate-release lovastatin.119

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.)

Extended-release tablets not recommended in patients requiring smaller reductions in cholesterol concentrations; may consider immediate-release lovastatin.119

Cautions for Lovastatin

Contraindications

  • Concomitant use with potent CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telaprevir, telithromycin).118 119 120 (See Specific Drugs and Foods under Interactions.)

  • Active liver disease or unexplained, persistent elevations of serum aminotransferases.1 116 117

  • 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.1 116 117

  • Known hypersensitivity to lovastatin or any ingredient in the formulation.1 116 117

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

Suppression of cholesterol biosynthesis could cause fetal harm.1 116 117 Congenital anomalies following intrauterine exposure to statins reported rarely.1 116 117

Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.1 116 117 If the patient becomes pregnant while taking the drug, immediately discontinue therapy and apprise the patient of the potential hazard to the fetus.1 116 117 118

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.1 116 117

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]) with or without acute renal failure secondary to myoglobinuria has been reported;1 116 117 rare fatalities have occurred.1

Risk of myopathy increased in patients receiving higher dosages of statins; patients with multisystem disease (e.g., renal or hepatic impairment), concurrent serious infections, or hypothyroidism; geriatric patients (>65 years of age); patients with small body frame and frailty; and patients undergoing surgery (i.e., during perioperative periods).119

Certain drug or food interactions also may increase risk of myopathy and/or rhabdomyolysis.1 118 119 120 (See Contraindications and also see Interactions.)

Myopathy and rhabdomyolysis reported with extended-release lovastatin, especially in geriatric patients initiating therapy at a dosage of 60 mg daily; therefore, lower initial dosages of extended-release lovastatin recommended in geriatric patients, particularly those with complicated medical conditions.119 (See Geriatric Patients under Dosage and Administration.)

May consider periodic monitoring of CK concentrations when initiating therapy or increasing dosage; however, there is no assurance that such monitoring will prevent myopathy.118 119 120

Discontinue if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected.1 116 117 118 119 120

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).1 116 117 118 119 120

Hepatic Effects

Associated with increases in serum aminotransferase (AST, ALT) concentrations.1 116 117

Pancreatitis,1 116 117 hepatitis (including chronic active hepatitis),1 116 117 cholestatic jaundice,1 116 117 fatty change in liver,1 116 117 increased serum alkaline phosphatase concentrations,1 116 117 increased serum γ-glutamyl transpeptidase concentrations,1 116 117 increased bilirubin concentrations,1 116 117 cirrhosis,1 116 117 fulminant hepatic necrosis,1 116 117 hepatoma,1 116 117 and fatal and nonfatal hepatic failure118 119 120 have been reported.1 116 117 118 119 120

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage201 ).118 119 120 Although manufacturers previously recommended more frequent monitoring,1 116 117 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

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt lovastatin therapy.118 119 120 If an alternate etiology is not found, do not restart lovastatin.118 119 120

Also see Hepatic Impairment under Cautions.

Hyperglycemic Effects

Increases in HbA1c and fasting serum glucose concentrations reported.118 119 120 200 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

Endogenous Steroid Production

Statins interfere with cholesterol synthesis and theoretically may blunt adrenal and/or gonadal steroid production.118 119 120

No effects on basal plasma cortisol concentrations, testosterone concentrations, or adrenal reserve observed with lovastatin.118 119 120 Effects on male fertility or on pituitary-gonadal axis in premenopausal women not fully established.118 119 120

If clinical evidence of endocrine dysfunction is present, evaluate patients appropriately.118 119 120

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).118 119 120

Cognitive Impairment

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) reported rarely.118 119 120

Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy).118 119 120 200 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

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.1 116 117

Use of Fixed Combinations

When used in fixed combination with extended-release niacin, consider the cautions, precautions, and contraindications associated with niacin.117

Specific Populations

Pregnancy

Category X.1 116 117 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Not known whether lovastatin is distributed into milk;1 116 117 however, other statins are distributed into milk.1 116 117 Use is contraindicated in nursing women; women who require lovastatin therapy should not breast-feed their infants.1 116 117 118 119 120

Lovastatin/extended-release niacin fixed combination (Advicor): Do not use in nursing women.120

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 or lovastatin in fixed combination with extended-release niacin not established in children or adolescents <20 or 18 years of age, respectively.116 117

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.1 116 117

Conventional tablets: 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

Extended-release lovastatin: Myopathy and rhabdomyolysis reported, especially in geriatric patients initiating therapy at 60 mg daily; therefore, dosage adjustments necessary.119 (See Geriatric Patients under Dosage and Administration.)

Lovastatin/extended-release niacin: Amylase concentrations appeared higher in patients ≥65 years of age compared with younger patients.120

Use with caution.119

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.1 116 117

Contraindicated in patients with active liver disease or unexplained, persistent increases in liver function test results.1 116 117

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.1 116 119

Interactions for Lovastatin

Metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.1 116

When used in fixed combination with extended-release niacin, consider interactions associated with niacin.120

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma lovastatin concentrations); increased risk of myopathy or rhabdomyolysis.118 119 120 Concomitant use contraindicated.118 119 120 (See Contraindications under Cautions.)

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Amiodarone

Increased risk of myopathy and/or rhabdomyolysis when used with another statin1

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

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

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

Antileukotrienes (e.g., zileuton)

Inhibition of lovastatin metabolism via CYP3A4

Concomitant use generally should be avoided or undertaken with caution

Antifungals, azoles

Itraconazole, ketoconazole, or posaconazole: Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and AUC and increased risk of myopathy and/or rhabdomyolysis1 116 118 119

Voriconazole: Possible inhibition of lovastatin metabolism, resulting in increased risk of myopathy and/or rhabdomyolysis118 119

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

Voriconazole: If concomitant use is unavoidable, consider adjusting lovastatin dosage118 119

Colchicine

Myopathy, including rhabdomyolysis, reported118 119

Use concomitantly with caution118 119

Cyclosporine

Increased lovastatin AUC and increased risk of myopathy and/or rhabdomyolysis1 116 118 119

Avoid concomitant use118 119

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 119 120

Digoxin

No effect on digoxin plasma concentrations118 119

Diltiazem

Increased AUC of total lovastatin acid; 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 119 120

Fibric acid derivatives (e.g., gemfibrozil)

Increased risk of myopathy and/or rhabdomyolysis1 116

Gemfibrozil: Increased AUC of lovastatin acid118 119

Gemfibrozil: Avoid concomitant use118 119 120

Other fibric acid derivatives: Use concomitantly with caution; weigh benefits against risks of concomitant use118 119

Fluvoxamine

Inhibition of lovastatin metabolism via CYP3A4

Concomitant use generally should be avoided or undertaken with caution

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 116 118 119

Avoid large quantities (>1 quart daily) of grapefruit juice1 118 119

HCV protease inhibitors (i.e., boceprevir, telaprevir)

Boceprevir or telaprevir: Inhibition of lovastatin metabolism via CYP3A4, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis118 119

Boceprevir or telaprevir: Concomitant use contraindicated118 119

HIV protease inhibitors

Inhibition of CYP3A4-dependent metabolism of lovastatin, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 116 118 119

Concomitant use contraindicated118 119

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 116 118 119

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

Metronidazole

Inhibition of lovastatin metabolism via CYP3A4

Concomitant use generally should be avoided or undertaken with caution

Nefazodone

Inhibition of lovastatin metabolism via CYP3A4, resulting in increased lovastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 116 118 119

Concomitant use contraindicated118 119

Niacin (antilipemic dosages [≥1 g daily])

Increased risk of myopathy and/or rhabdomyolysis1 116

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

Propranolol

No clinically important pharmacokinetic or pharmacodynamic interaction reported118 119

Ranolazine

Possible increased risk of myopathy, including rhabdomyolysis118 119

If used concomitantly, may consider adjusting lovastatin dosage118 119

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

Troleandomycin

Inhibition of lovastatin metabolism via CYP3A4

Concomitant use generally should be avoided or undertaken with caution

Verapamil

Increased plasma lovastatin concentrations; increased risk of myopathy and/or rhabdomyolysis, particularly with higher lovastatin dosages1 116 118 119

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 119 120

Warfarin

Bleeding and/or increased PT observed1 116 117

Closely monitor PT until stabilized if lovastatin is initiated or dosage is adjusted in patients receiving a coumarin anticoagulant;1 116 117 thereafter, monitor PT at intervals usually recommended for patients receiving warfarin1 116 117

Lovastatin Pharmacokinetics

Absorption

Bioavailability

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

Conventional tablets: Absolute bioavailability is <5%.1

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

Lovastatin/extended-release niacin fixed-combination tablets (Advicor): Bioavailability of 1 tablet containing 1 g of extended-release niacin and 40 mg of lovastatin differs from that of 2 tablets each containing 500 mg of extended-release niacin and 20 mg of lovastatin.117 (See Dosage: Lovastatin/Extended-release Niacin Fixed-combination Tablets [Advicor], under Dosage and Administration.)

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.

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 20–25°C; protect from light.1 118

Extended-release Tablets

20–25°C (may be exposed to 15–30°C).116 119 Avoid excessive heat and humidity.116

Lovastatin/Extended-release Niacin Fixed-combination Tablets (Advicor)

20–25°C.117

Actions

  • Prodrug requiring hydrolysis in vivo for activity.1 116

  • Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.1 116 Reduces serum concentrations of total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglycerides.1 116

  • 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 (i.e., therapeutic life-style changes, including dietary management, weight control, physical activity, and management of potentially contributory disease [e.g., diabetes mellitus]).

  • Importance of informing patients about risks, especially rhabdomyolysis, associated with statins alone or combined with other drugs.1 116 117 Importance of patients promptly reporting muscle pain, tenderness, or weakness;1 116 117 brown urine; flu-like symptoms; and malaise.

  • Risk of adverse hepatic effects.118 119 120 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).118 119 120

  • Risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).118 119 120 200

  • Risk of increased glucose concentrations and development of type 2 diabetes.118 119 120 200 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.1 116 117

  • Importance of avoiding breast-feeding during therapy.118 119 120

  • 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.1 116 117 (See Cautions.)

Preparations

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

* 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

Mevacor

Merck

40 mg*

Lovastatin Tablets

Mevacor

Merck

Tablets, extended-release

20 mg

Altoprev

Watson

40 mg

Altoprev

Watson

60 mg

Altoprev

Watson

Lovastatin Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

20 mg with Extended-release Niacin 500 mg

Advicor

Abbott

20 mg with Extended-release Niacin 750 mg

Advicor

Abbott

20 mg with Extended-release Niacin 1 g

Advicor

Abbott

40 mg with Extended-release Niacin 1 g

Advicor

Abbott

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Advicor 1000-20MG 24-hr Tablets (ABBOTT): 60/$296.00 or 180/$855.95

Advicor 1000-40MG 24-hr Tablets (ABBOTT): 90/$477.99 or 180/$950.92

Advicor 500-20MG 24-hr Tablets (ABBOTT): 90/$385.00 or 180/$756.95

Advicor 750-20MG 24-hr Tablets (ABBOTT): 60/$276.00 or 180/$815.99

Altoprev 20MG 24-hr Tablets (SHIONOGI PHARMA): 30/$399.98 or 90/$1,109.93

Altoprev 60MG 24-hr Tablets (SHIONOGI PHARMA): 30/$427.99 or 90/$1,255.97

Lovastatin 10MG Tablets (ACTAVIS ELIZABETH): 45/$47.99 or 90/$55.96

Lovastatin 20MG Tablets (ACTAVIS ELIZABETH): 30/$22.99 or 90/$59.99

Lovastatin 40MG Tablets (ACTAVIS ELIZABETH): 30/$35.99 or 90/$98.99

Mevacor 40MG Tablets (MERCK SHARP &amp; DOHME): 30/$146.00 or 90/$409.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 23, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, 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.

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