After a comprehensive review of all available data, the FDA is requesting all statin manufacturers to remove the contraindication in the prescribing information against using statins in pregnant patients. Although statin therapy should be discontinued in most pregnant patients, health care providers should consider the ongoing therapeutic needs of the individual patient, especially patients at very high risk of cardiovascular events during pregnancy, such as patients with homozygous familial hypercholesterolemia or those with established cardiovascular disease. Additionally, breastfeeding is still not recommended in patients taking a statin; health care providers should determine whether it is better to temporarily stop statin therapy while breastfeeding or to continue statin therapy and not have the patient breastfeed. If ongoing statin treatment is necessary, infant formula and other alternatives are available. The FDA expects that removing the contraindication will enable health care providers and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke.
Further information is available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy.
Dosage guidance:
Dosing: Lovastatin 40 to 80 mg/day is considered a moderate-intensity statin (generally reduces low-density lipoprotein-cholesterol [LDL-C] by ~30% to 49%). Lovastatin 20 mg/day is considered a low-intensity statin (reduces LDL-C <30%). If LDL-C must be lowered ≥50%, select a high-intensity statin (atorvastatin or rosuvastatin). Assess response ~1 to 3 months after therapy initiation or dose adjustment and every 3 to 12 months thereafter (Ref).
Clinical considerations: Use in conjunction with lifestyle modification (eg, diet, exercise). When initiating therapy and selecting dose intensity, consider age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions (Ref).
Heterozygous familial hyperlipidemia (alternative agent):
Note: Use of lovastatin should be limited to patients unable to tolerate a high-intensity statin (atorvastatin or rosuvastatin). Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
Patients unable to tolerate high-intensity therapy:
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal (Ref).
Extended release: 40 to 60 mg once daily at bedtime (Ref).
Prevention of atherosclerotic cardiovascular disease:
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration based on estimated 10-year ASCVD risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, consider switching to a high-intensity statin (atorvastatin or rosuvastatin); additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Patients without d iabetes, 40 to 75 years of age, and LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; in patients with a baseline LDL-C ≥160 mg/dL, statin therapy is usually recommended (Ref).
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 40 to 60 mg once daily at bedtime to reduce LDL-C by ~30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Ref).
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 40 to 60 mg once daily at bedtime to reduce LDL-C by ~30% to 49% (Ref).
ASCVD 10-year risk ≥20% (alternative agent):
Note: Use of lovastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal (Ref).
Extended release: 40 to 60 mg once daily at bedtime (Ref).
Patients with diabetes:
40 to 75 years of age without additional ASCVD risk factors:
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 40 to 60 mg once daily at bedtime to reduce LDL-C by ~30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% or multiple ASCVD risk factors (alternative agent):
Note: Use of lovastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal (Ref).
Extended release: 40 to 60 mg once daily at bedtime (Ref).
Patients with LDL-C ≥190 mg/dL and 20 to 75 years of age (regardless of ASCVD risk estimate or coexisting diabetes mellitus) (alternative agent):
Note: Use of lovastatin should be limited to patients unable to tolerate a high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal (Ref).
Extended release: 40 to 60 mg once daily at bedtime (Ref).
Secondary prevention in patients with established atherosclerotic cardiovascular disease (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease) (alternative agent):
Note: Use of lovastatin should be limited to patients unable to tolerate a high-intensity statin. Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 to 80 mg once daily with evening meal (Ref).
Extended release: 40 to 60 mg once daily at bedtime (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl <30 mL/minute: Use with caution and carefully consider doses >20 mg/day.
No dosage adjustment provided in manufacturer’s labeling (has not been studied).
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Ref).
Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of lovastatin. If muscle symptoms recur, discontinue lovastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Immediate release: Refer to adult dosing; Extended release: Initial: Consider starting a lower dose of 20 mg once daily at bedtime and titrate as tolerated (Ref).
(For additional information see "Lovastatin: Pediatric drug information")
Dyslipidemia; prevention coronary artery disease (CAD): Adolescents ≥18 years: Oral: Immediate release: Initial: 20 mg once daily with evening meal, then adjust at 4-week intervals; maximum daily dose: 80 mg/day. Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response.
Heterozygous familial hypercholesterolemia: Note: Begin treatment if after adequate (eg, 6 month) trial of lifestyle/diet modifications the following are present: LDL-C ≥190 mg/dL or LDL-C remains ≥160 mg/dL with either a positive family history of premature cardiovascular disease or at least 1 high-level or 2 moderate-level risk factors. Females must be ≥1 year postmenarche (Ref).
Children ≥10 years and Adolescents ≤17 years: Oral: Immediate release: Initial: 10 mg once daily with evening meal (Ref); if target LDL-C levels are not reached within 3 months, increase dose in 10 mg increments every 3 months until target LDL-C achieved; usual effective range: 10 to 40 mg once daily; maximum daily dose: 80 mg/day (Ref). Lower initial doses or maximum daily doses may be necessary for some concomitant medications (eg, amiodarone, verapamil, danazol, diltiazem). Note: Children 8 to <10 years of age are not typically treated unless severe primary hyperlipidemias and high-risk condition associated with high morbidity; data for the use of lovastatin in these younger patients is lacking (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥10 years and Adolescents: Discontinue use until symptoms can be evaluated; check creatine phosphokinase (CPK) level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism; reduced renal or hepatic function; rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of lovastatin and retitrate. If muscle symptoms recur, discontinue lovastatin use. After muscle symptom resolution, may then reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
CrCl <30 mL/minute: Immediate release: Children ≥10 years and Adolescents: Doses exceeding 20 mg/day should be carefully considered and implemented cautiously
There are no dosage adjustment provided in manufacturer's labeling (has not been studied); use is contraindicated in active liver disease or unexplained transaminase elevations.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Infection: Infection (11% to 16%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (≥2x ULN:11%)
1% to 10%:
Dermatologic: Skin rash (1%)
Gastrointestinal: Abdominal pain (3%), constipation (3% to 4%), diarrhea (3%), flatulence (5%)
Hepatic: Increased serum transaminases (≥3x ULN: 2%; including increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin)
Nervous system: Dizziness (1%), headache (7% to 8%), pain (3% to 5%)
Neuromuscular & skeletal: Asthenia (2%), back pain (5%), muscle cramps (1%), myalgia (3%)
Ophthalmic: Blurred vision (1%)
Respiratory: Flu-like symptoms (5%), sinusitis (4% to 6%)
<1%:
Cardiovascular: Chest pain
Dermatologic: Alopecia, pruritus
Gastrointestinal: Acid regurgitation, vomiting, xerostomia
Nervous system: Insomnia, paresthesia
Neuromuscular & skeletal: Arthralgia, lower extremity pain, myopathy, shoulder pain
Ophthalmic: Eye irritation
Postmarketing:
Cardiovascular: Flushing, vasculitis
Dermatologic: Changes in nails, changes of hair, cutaneous nodule, erythema multiforme, skin discoloration, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, xeroderma
Endocrine & metabolic: Gynecomastia, increase in fasting plasma glucose, increased gamma-glutamyl transferase, loss of libido, thyroid dysfunction
Gastrointestinal: Anorexia, dry mucous membranes, pancreatitis
Genitourinary: Cystitis (interstitial; Huang 2015), erectile dysfunction
Hematologic & oncologic: Elevated glycosylated hemoglobin, eosinophilia, hemolytic anemia, increased erythrocyte sedimentation rate, leukopenia, positive ANA titer, purpuric disease, thrombocytopenia
Hepatic: Cholestatic jaundice, chronic active hepatitis, hepatic cirrhosis, hepatic failure, hepatic neoplasm, hepatitis
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Nervous system: Anxiety, chills, cognitive dysfunction (including amnesia, confusion, memory impairment), cranial nerve disorder (including dysgeusia, facial paresis, impairment of extraocular movement), depression, malaise, peripheral nerve palsy, peripheral neuropathy, psychic disorder, vertigo
Neuromuscular & skeletal: Arthritis, dermatomyositis, lupus-like syndrome, polymyalgia rheumatica, rhabdomyolysis, tremor
Ophthalmic: Ophthalmoplegia, progression of cataract
Respiratory: Dyspnea, interstitial pulmonary disease
Miscellaneous: Fever
Hypersensitivity to lovastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; concomitant use of strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, posaconazole, voriconazole, protease inhibitors [including boceprevir and telaprevir], telithromycin, cobicistat-containing products); pregnancy; breastfeeding
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use of cyclosporine
Concerns related to adverse effects:
• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia. If a patient develops diabetes mellitus during therapy, continue use of lovastatin and encourage patient to adhere to healthy lifestyle regimens (eg, heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight) (ACC/AHA [Grudy 2019]).
• Endocrine effects: Reduced cholesterol synthesis as a result of therapy could theoretically lead to reduced adrenal or gonadal steroid hormone production; clinical trial data are inconsistent in regard to the effect on basal steroid hormone levels. Patients with signs/symptoms of endocrine dysfunction should be evaluated as clinically indicated; use caution with concomitant medications (eg, spironolactone, cimetidine, ketoconazole) that may reduce steroid hormone levels/activity.
• Hepatotoxicity: Persistent elevations in serum transaminases have been reported; upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels. Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. If an alternate etiology is not identified, do not restart lovastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.
• Myopathy/rhabdomyolysis: Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, protease inhibitors), cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day); if concurrent use is warranted, consider lower starting and maintenance doses of lovastatin. Use caution in patients with inadequately treated hypothyroidism and those taking other drugs associated with myopathy (eg, colchicine), ≥65 years of age, and women; these patients are predisposed to myopathy. Immune-mediated necrotizing myopathy associated with HMG-CoA reductase inhibitor use has also been reported. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Discontinue therapy if markedly elevated CPK levels occur or if myopathy is diagnosed/suspected; consider treatment with immunosuppressants and additional neuromuscular and serologic testing. Prior to initiating a different HMG-CoA reductase inhibitor, consider risk of immune-mediated necrotizing myopathy; monitor closely.
Disease-related concerns:
• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated in patients with active liver disease or unexplained transaminase elevations.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Renal impairment: Use with caution in patients with renal impairment; risk of myopathy is increased.
Special populations:
• Older adult: Use with caution in patients with advanced age, these patients are predisposed to myopathy.
• Surgical patients: Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 10 mg, 20 mg, 40 mg
Tablet Extended Release 24 Hour, Oral:
Altoprev: 20 mg, 40 mg, 60 mg [contains corn starch, fd&c yellow #6 (sunset yellow)]
May be product dependent
Tablet, 24-hour (Altoprev Oral)
20 mg (per each): $43.33
40 mg (per each): $43.33
60 mg (per each): $43.33
Tablets (Lovastatin Oral)
10 mg (per each): $1.35 - $1.61
20 mg (per each): $2.25 - $2.71
40 mg (per each): $4.06 - $4.87
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 20 mg, 40 mg
Oral: Administer IR tablet with the evening meal. Administer ER tablet at bedtime; do not cut, crush, or chew.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.
Oral:
Immediate release tablets: Take with the evening meal.
Extended release tablets: Take at bedtime; do not crush or chew.
Dyslipidemia, prevention of coronary artery disease: Adjunct to dietary therapy in adolescent patients (10 to 17 years of age, females >1 year postmenarche) with heterozygous familial hypercholesterolemia having low-density lipoprotein (LDL) >189 mg/dL, or LDL >160 mg/dL with positive family history of premature cardiovascular disease (CVD), or LDL >160 mg/dL with the presence of at least 2 other CVD risk factors.
Heterozygous familial hyperlipidemia: Adjunct to dietary therapy to decrease elevated serum total and LDL-cholesterol concentrations in primary hypercholesterolemia (heterozygous familial and nonfamilial).
Primary prevention of atherosclerotic cardiovascular disease: Reduce the risk of cardiovascular events in patients without symptomatic atherosclerotic cardiovascular disease (ASCVD) but who have multiple ASCVD risk factors.
Secondary prevention of atherosclerotic cardiovascular disease: Slow progression of coronary atherosclerosis in patients with ASCVD.
HMG-CoA reductase inhibitors (when referred to as "statins") may be confused with nystatin.
Lovastatin may be confused with atorvastatin, Leustatin, Livostin, Lotensin, nystatin, pitavastatin.
Mevacor may be confused with Benicar, Lipitor.
Lovacol [Chile and Finland] may be confused with Levatol brand name for penbutolol [U.S.]
Lovastin [Malaysia, Poland, and Singapore] may be confused with Livostin brand name for levocabastine [multiple international markets]
Mevacor [US, Canada, and multiple international markets] may be confused with Mivacron brand name for mivacurium [multiple international markets]
Substrate of CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Amiodarone: May increase the serum concentration of Lovastatin. Management: Consider using a non-interacting statin (pravastatin, pitavastatin) in patients on amiodarone. If combined, limit the lovastatin dose to 40 mg daily and monitor for lovastatin toxicities (eg, myalgia, liver function test elevations, rhabdomyolysis). Risk D: Consider therapy modification
AmLODIPine: May increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Lovastatin. Risk C: Monitor therapy
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Lovastatin. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lovastatin. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Lovastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lovastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Lovastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Dabigatran Etexilate: Lovastatin may enhance the anticoagulant effect of Dabigatran Etexilate. Risk C: Monitor therapy
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Danazol: May increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving danazol. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
DilTIAZem: May increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving diltiazem. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Dronedarone: May increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving dronedarone. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Elbasvir and Grazoprevir: May increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May decrease the serum concentration of Lovastatin. Encorafenib may increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Erythromycin (Systemic): May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). This applies to atorvastatin, lovastatin and simvastatin. Risk C: Monitor therapy
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosamprenavir: May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Grapefruit Juice: May increase serum concentrations of the active metabolite(s) of Lovastatin. Grapefruit Juice may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Itraconazole: May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lanthanum: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Letermovir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Levamlodipine: May increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Lomitapide: May increase the serum concentration of Lovastatin. Management: Consider reducing lovastatin doses during concomitant treatment with lomitapide, and monitor for signs and symptoms of muscle toxicity. Specific dosing recommendations are not presently available. Risk D: Consider therapy modification
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Pectin: May diminish the therapeutic effect of Lovastatin. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Ranolazine: May increase the serum concentration of Lovastatin. Ranolazine may also enhance the distribution of lovastatin to specific cells/tissues/organs where P-glycoprotein is present in large amounts (eg, brain, T-lymphocytes, testes, etc.). Management: Consider a lovastatin dose reduction if combined with ranolazine. An American Heart Association scientific statement recommends limiting lovastatin doses to 20 mg daily when used with ranolazine. Monitor closely for lovastatin toxicity. Risk D: Consider therapy modification
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Roxadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor therapy
Simeprevir: May increase the serum concentration of Lovastatin. Risk C: Monitor therapy
St John's Wort: May decrease serum concentrations of the active metabolite(s) of HMG-CoA Reductase Inhibitors (Statins). Management: Consider avoiding the concomitant administration of St John's Wort with atorvastatin, lovastatin and simvastatin in order to avoid the potential for decreased effects statins. If coadministered, monitor for decreased statin efficacy. Risk D: Consider therapy modification
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ticagrelor: May increase the serum concentration of Lovastatin. Management: Limit lovastatin doses to 40 mg/day if coadministered with ticagrelor. Risk D: Consider therapy modification
Tipranavir: May increase the serum concentration of Lovastatin. Risk X: Avoid combination
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Verapamil: May increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving verapamil. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors (Statins) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities. Avoid concomitant use of voxilaprevir with rosuvastatin or pitavastatin, and limit pravastatin doses to 40 mg daily. Risk D: Consider therapy modification
Food decreases the bioavailability of lovastatin extended release tablets and increases the bioavailability of lovastatin immediate release tablets. Lovastatin serum concentrations may be increased if taken with grapefruit juice. Management: Avoid combination.
Lovastatin is contraindicated in females who may become pregnant.
Adequate contraception is recommended if an HMG-CoA reductase inhibitor is required in females of reproductive potential. Females planning a pregnancy should discontinue the HMG-CoA reductase inhibitor 1 to 2 months prior to attempting to conceive (AHA/ACC [Grundy 2019]).
Lovastatin is contraindicated in pregnant females.
There are reports of congenital anomalies following maternal use of HMG-CoA reductase inhibitors in pregnancy; however, maternal disease, differences in specific agents used, and the low rates of exposure limit the interpretation of the available data (Godfrey 2012; Lecarpentier 2012). Cholesterol biosynthesis may be important in fetal development; serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid lowering medications temporarily during pregnancy is not expected to have significant impact on the long term outcomes of primary hypercholesterolemia treatment.
Lovastatin should be discontinued immediately if an unplanned pregnancy occurs during treatment.
It is not known if lovastatin is present in breast milk. Due to the potential for serious adverse reactions in a breastfed infant, use while breastfeeding is contraindicated by the manufacturer.
Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 6 weeks and the diet should be continued during drug therapy. Avoid intake of grapefruit juice; may increase toxicity. Immediate release tablet should be taken with the evening meal.
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2019]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Lovastatin acts by competitively inhibiting 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).
Onset of action: LDL-cholesterol reductions: 3 days
Absorption: 30% absorbed but less than 5% reaches the systemic circulation due to an extensive first-pass effect; increased with extended release tablets when taken in the fasting state
Protein binding: >95%
Metabolism: Hepatic; extensive first-pass effect; hydrolyzed to β-hydroxyacid (active)
Bioavailability: Increased with extended release tablets
Half-life elimination: 1.1-1.7 hours
Time to peak, serum: Immediate release: 2-4 hours; extended release: 12-14 hours
Excretion: Feces (~80% to 85%); urine (10%)
Altered kidney function: Plasma concentrations of total inhibitors are increased 2-fold in severe renal insufficiency (CrCl <30 mL/minute).
Older adult: The mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% in elderly patients 70 to 78 years of age compared with patients 18 to 30 years of age.
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