Lovastatin (Monograph)
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
Introduction
Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).1 2 3 4 5 118 119
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.1 83 118 119
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 61 70 74 75 76 91 92 93 118 119
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.336 337 338 350 400
AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of ASCVD risk reduction.400 Patients with established ASCVD or high risk of ASCVD should also be treated with a statin.400
Because relative ASCVD risk reduction is correlated with degree of LDL-cholesterol lowering, use maximum tolerated intensity of a statin to achieve greatest benefit.400 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%).400 AHA/ACC considers lovastatin 40–80 mg daily to be a moderate-intensity statin.400
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.400
When considering whether to initiate statin therapy for primary prevention, AHA/ACC recommends an individualized approach and shared decision making between patient and clinician.400 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%.400
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† [off-label] (diabetic dyslipidemia),50 52 cardiac† [off-label]50 53 54 102 or renal transplantation† [off-label],50 54 103 nephrotic syndrome† [off-label] (nephrotic hyperlipidemia),27 50 55 or distal ileal bypass surgery† [off-label].23 33 56
Reduction of total cholesterol, LDL cholesterol, and/or apolipoprotein B in patients with hypoalphalipoproteinemia†98 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
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.400
-
Periodically reinforce adherence to lifestyle modifications.400 Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of ASCVD.400
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
Dosage modifications may be necessary when used concomitantly with certain drugs (see Specific Drugs and Foods under Interactions).1
Pediatric Patients
Dyslipidemias
Conventional Tablets
OralChildren 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
Reduction in Risk of Cardiovascular Events
Oral
Use maximally tolerated statin intensity to achieve optimal ASCVD risk reduction.400 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%).400
The AHA/ACC guideline panel considers lovastatin 40–80 mg daily to be a moderate-intensity statin.400
Dyslipidemias
Conventional Tablets
OralUsual 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
OralRecommended 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
Prescribing Limits
Pediatric Patients
Dyslipidemias
Conventional Tablets
OralChildren 10–17 years of age: Maximum 40 mg daily.1 118
Adults
Prevention of Cardiovascular Events or Management of Dyslipidemias
Conventional Tablets
OralMaximum 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
-
Lactation.1
-
Known hypersensitivity to lovastatin or any ingredient in the formulation.1 118
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.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.)
AHA/ACC recommends measurement of CK levels in patients with severe statin-associated muscle symptoms; however, routine monitoring not useful.400
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 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.200 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.350 400
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
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.400
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
All statins were previously contraindicated in pregnant women because fetal risk was thought to outweigh any possible benefit.405 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.405 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.400 405 Consider patient's individual risks and benefits.405
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.405
Increased risk of miscarriage reported in pregnant women exposed to statins; however, not clear whether drug-related or due to other confounding factors.400 405
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 Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.400 405
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.)
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.400
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
Drug Interactions
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 |
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 |
|
Colchicine |
||
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 |
||
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: 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 |
|
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 |
|
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 |
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
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
-
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 to notify their clinician if they become pregnant during therapy.405
-
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.)
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
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 2024, Selected Revisions January 1, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: 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. http://www.ncbi.nlm.nih.gov/pubmed/6918220?dopt=AbstractPlus
5. Tobert JA, Bell GD, Birtwell J et al. Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in healthy volunteers. J Clin Invest. 1982; 69:913-9. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=370145&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/6918402?dopt=AbstractPlus
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7. Stacpoole PW, Alig J. Advances in the treatment of coronary heart disease: fish oils, cholestyramine, and mevinolin. Cardiovasc Clin. 1987; 18:267-79. http://www.ncbi.nlm.nih.gov/pubmed/3300984?dopt=AbstractPlus
8. Illingworth DR. Mevinolin plus colestipol in therapy for severe heterozygous familial hypercholesterolemia. Ann Intern Med. 1984; 101:598-604. http://www.ncbi.nlm.nih.gov/pubmed/6567462?dopt=AbstractPlus
9. Illingworth DR, Sexton GJ. Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia. J Clin Invest. 1984; 74:1972-8. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=425384&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/6569064?dopt=AbstractPlus
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