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Lovastatin

Pronunciation

Pronunciation

(LOE va sta tin)

Index Terms

  • Mevinolin
  • Monacolin K

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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Tablet, Oral:

Mevacor: 20 mg, 40 mg

Generic: 10 mg, 20 mg, 40 mg

Tablet Extended Release 24 Hour, Oral:

Altoprev: 20 mg, 40 mg, 60 mg [contains fd&c yellow #6 (sunset yellow)]

Brand Names: U.S.

  • Altoprev
  • Mevacor

Pharmacologic Category

  • Antilipemic Agent, HMG-CoA Reductase Inhibitor

Pharmacology

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).

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

Metabolism

Hepatic; extensive first-pass effect; hydrolyzed to β-hydroxyacid (active)

Excretion

Feces (~80% to 85%); urine (10%)

Onset of Action

LDL-cholesterol reductions: 3 days

Time to Peak

Serum: Immediate release: 2-4 hours; extended release: 12-14 hours

Half-Life Elimination

1.1-1.7 hours

Protein Binding

>95%

Special Populations: Renal Function Impairment

Plasma concentrations of total inhibitors are increased 2-fold in severe renal insufficiency (CrCl < 30 ml/min). concentration.

Use: Labeled Indications

Adjunct to dietary therapy to decrease elevated serum total and LDL-cholesterol concentrations in primary hypercholesterolemia

Primary prevention of coronary artery disease (patients without symptomatic disease with average to moderately elevated total and LDL-cholesterol and below average HDL-cholesterol); slow progression of coronary atherosclerosis in patients with coronary heart disease and reduce the risk of myocardial infarction, unstable angina, and coronary revascularization procedures.

Adjunct to dietary therapy in adolescent patients (10-17 years of age, females >1 year postmenarche) with heterozygous familial hypercholesterolemia having 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 two other CVD risk factors

Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) who are greater than 75 years of age or not a candidate for high-intensity statin therapy; in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater and not a candidate for high-intensity statin therapy; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone 2013). The American Heart Association (AHA) recommends statin therapy (unless contraindicated) for all coronary artery bypass graft (CABG) surgery patients to help maintain long-term graft patency and help obtain the highest level of physical health and quality of life (AHA [Kulik 2015]). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli 2013]).

Contraindications

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; breast-feeding

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use of cyclosporine

Dosage

Adolescents 10-17 years: Oral: Immediate release tablet:

LDL reduction <20%: Initial: 10 mg daily with evening meal

LDL reduction ≥20%: Initial: 20 mg daily with evening meal

Usual range: 10-40 mg once daily with evening meal, then adjust dose at 4-week intervals; maximum dose per manufacturer: 40 mg daily

Adults: Oral:

Immediate release: Initial: 20 mg once daily with evening meal, then adjust at 4-week intervals; maximum dose: 80 mg daily

Extended release: Initial: 20, 40, or 60 mg once daily at bedtime, then adjust at 4-week intervals; maximum dose: 60 mg daily

Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response. For patients requiring smaller reductions in cholesterol, the use of the extended release tablet is not recommended; consider use of immediate release formulation.

Prevention of cardiovascular disease: ACC/AHA Blood Cholesterol Guideline recommendations to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Stone 2013): Adults ≥21 years: Oral:

Primary prevention:

LDL-C ≥190 mg/dL: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin)

Type 1 or 2 diabetes and age 40-75 years: Moderate intensity therapy: Immediate release: 40 mg once daily

Type 1 or 2 diabetes, age 40-75 years, and an estimated 10-year ASCVD risk ≥7.5%: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin)

Age 40-75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate to high intensity therapy: Immediate release: 40 mg once daily or consider using high intensity statin therapy (eg, atorvastatin or rosuvastatin)

Secondary prevention:

Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik 2015]) and:

Age ≤75 years: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin)

Age >75 years or not a candidate for high intensity therapy: Moderate intensity therapy: Immediate release: 40 mg once daily

Elderly: Immediate release: Refer to adult dosing; Extended release: Initial: 20 mg once daily at bedtime

Dosage adjustment for lovastatin with concomitant medications:

Amiodarone: Maximum recommended lovastatin dose (extended release and immediate release): 40 mg daily

Danazol, diltiazem, dronedarone, or verapamil: Initial lovastatin (immediate release) dose: 10 mg daily; Maximum recommended lovastatin (extended release and immediate release) dose: 20 mg daily

Lomitapide: Consider lovastatin dose reduction (per lomitapide manufacturer).

Dosage adjustment for toxicity:

Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Stone 2013).

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 (Stone 2013).

Dosage adjustment in renal impairment: CrCl <30 mL/minute: Use with caution and carefully consider doses >20 mg/day.

Dosage adjustment in hepatic impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Administration

Administer immediate release tablet with the evening meal. Administer extended release tablet at bedtime; do not crush or chew.

Dietary Considerations

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 large quantities of grapefruit juice (≥1 quart/day); 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).

Storage

Tablet, immediate release: Store at 20°C to 25°C (68°F to 77°F). Protect from light

Tablet, extended release: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Avoid excessive heat and humidity.

Drug Interactions

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Consider therapy modification

Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Lovastatin. Monitor therapy

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification

Boceprevir: May increase the serum concentration of Lovastatin. Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. 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. Consider therapy modification

Clarithromycin: May increase the serum concentration of Lovastatin. Avoid combination

Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): May increase the serum concentration of Lovastatin. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lovastatin. Avoid combination

Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Danazol: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Concurrent use of simvastatin with danazol is contraindicated. Initiate lovastatin at an adult maximum dose of 10 mg/day, and do not exceed 20 mg/day, when danazol is given concomitantly. Fluvastatin, pravastatin and rosuvastatin may pose lower risk. Consider therapy modification

DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diltiazem: Lovastatin may increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Lovastatin. Management: Initiate lovastatin at a maximum adult dose of 10 mg/day, and do not exceed 20 mg/day, in patients receiving diltiazem. Monitor closely for signs of HMG-CoA reductase inhibitor toxicity (e.g., myositis, rhabdomyolysis). Consider therapy modification

Dronedarone: May increase the serum concentration of Lovastatin. Management: Limit lovastatin to a maximum of 20 mg/day (in adults). Increase monitoring for signs of lovastatin toxicity (e.g., myopathy, rhabdomyolysis). Consider therapy modification

Efavirenz: May decrease the serum concentration of Lovastatin. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erythromycin (Systemic): May increase the serum concentration of Lovastatin. Avoid combination

Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Monitor therapy

Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Fluconazole: May increase the serum concentration of Lovastatin. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. 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. Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Lovastatin. Gemfibrozil may increase the serum concentration of Lovastatin. More specifically, gemfibrozil may increase the serum concentrations of lovastatin acid (active form of parent drug). Avoid combination

Grapefruit Juice: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider avoiding concurrent use of GFJ (especially larger amounts) with lovastatin, simvastatin, or atorvastatin. Consider using a lower statin dose or a statin that is less likely to interact when possible. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification

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. Avoid combination

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Mifepristone: May increase the serum concentration of Lovastatin. Management: Avoid lovastatin during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Greatest concern with niacin 1 g/d or greater. Avoid simvastatin 80 mg with niacin 1 g or greater in Chinese patients. Do not exceed 40 mg/d of simva or lovastatin with Niaspan. Use of niacin with rosuvastatin 40 mg is contraindicated (Canadian label). Consider therapy modification

Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

PAZOPanib: HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of PAZOPanib. Specifically, the risk for increased serum transaminase concentrations may be increased. Management: Simvastatin is specifically implicated in this interaction. There is a lack of data regarding the risk with other statins, but caution appears warranted with any statins. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Lovastatin. Avoid combination

QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Consider therapy modification

Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Ranolazine: May enhance the myopathic (rhabdomyolysis) effect of Lovastatin. 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 (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination

Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification

Sacubitril: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of Lovastatin. Monitor therapy

St Johns Wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider avoiding the concomitant administration of St Johns Wort with interacting HMG-CoA reductase inhibitors in order to avoid the potential for decreased antilipemic effects. Monitor for decreased effects during concomitant therapy. Consider therapy modification

St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Telaprevir: May increase the serum concentration of Lovastatin. Avoid combination

Telithromycin: May increase the serum concentration of Lovastatin. Avoid combination

Ticagrelor: May increase the serum concentration of Lovastatin. Management: Avoid using doses of lovastatin greater than 40 mg/day with ticagrelor. This specific recommendation is found in the U.S. prescribing information but not in the Canadian product monograph. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy

Verapamil: May increase the serum concentration of Lovastatin. Management: Initiate lovastatin at a maximum adult dose of 10 mg/day, and do not exceed 20 mg/day, in patients receiving verapamil. Monitor closely for signs of HMG-CoA reductase inhibitor toxicity (e.g., myositis, rhabdomyolysis). Consider therapy modification

Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

Frequency not always defined. Percentages as reported with immediate release tablets; similar adverse reactions seen with extended release tablets.

Central nervous system: Headache (2% to 3%), dizziness (≤1%)

Dermatologic: Rash (≤1%)

Gastrointestinal: Flatulence (4% to 5%), constipation (2% to 4%), abdominal pain (2% to 3%), diarrhea (2% to 3%), nausea (2% to 3%), dyspepsia (1% to 2%)

Genitourinary: Cystitis (interstitial; Huang 2015)

Neuromuscular & skeletal: Increased CPK (>2x normal) (11%), myalgia (2% to 3%), weakness (1% to 2%), muscle cramps (≤1%)

Ocular: Blurred vision (≤1%)

<1% (Limited to important or life-threatening): Acid regurgitation, alopecia, amnesia (reversible), arthralgia, chest pain, cognitive impairment (reversible), confusion (reversible), dermatomyositis, diabetes mellitus (new onset), eye irritation, increased blood glucose, increased glycosylated hemoglobin (HbA1c), insomnia, leg pain, memory disturbance (reversible), memory impairment (reversible), paresthesia, pruritus, vomiting, xerostomia

Additional class-related events or case reports (not necessarily reported with lovastatin therapy): Alteration in taste, anaphylaxis, angioedema, anorexia, anxiety, arthritis, cataracts, chills, cholestatic jaundice, cirrhosis, depression, dryness of skin/mucous membranes, dyspnea, eosinophilia, erectile dysfunction, erythema multiforme, facial paresis, fatty liver, fever, flushing, fulminant hepatic necrosis, gynecomastia, hemolytic anemia, hepatic failure (fatal and nonfatal), hepatitis, hepatoma, hyperbilirubinemia, hypersensitivity reaction, immune-mediated necrotizing myopathy (IMNM), impaired extraocular muscle movement, impotence, increased alkaline phosphatase, increased ESR, increased GGT, increased transaminases, interstitial lung disease, leukopenia, libido decreased, malaise, myopathy, nail changes, nodules, ophthalmoplegia, pancreatitis, peripheral nerve palsy, peripheral neuropathy, photosensitivity, polymyalgia rheumatica, positive ANA, psychic disturbance, purpura, renal failure (secondary to rhabdomyolysis), rhabdomyolysis, skin discoloration, Stevens-Johnson syndrome, systemic lupus erythematosus-like syndrome, thrombocytopenia, thyroid dysfunction, toxic epidermal necrolysis, tremor, urticaria, vasculitis, vertigo

Warnings/Precautions

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.

• Hepatotoxicity: 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. 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.

• Immune-mediated necrotizing myopathy (IMNM): IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be used for treatment.

• Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of other lipid-lowering medications (eg, fibric acid derivatives, or niacin at doses ≥1 g/day) or during concurrent use with potent CYP3A4 inhibitors. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.

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.

• Renal impairment: Use with caution in patients with renal impairment; risk of myopathy is increased.

Concurrent drug therapy issues:

• High potential for interactions: Concomitant use of lovastatin with some drugs may require cautious use, may not be recommended, may require dosage adjustments, or may be contraindicated.

Special populations:

• Elderly: Use with caution in patients with advanced age, these patients are predisposed to myopathy.

• Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines (Fleisher 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative 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.

Monitoring Parameters

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):

Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.

Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function 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: Liver enzyme tests at baseline and repeated when clinically indicated. Measure CPK when myopathy is being considered or may measure CPK periodically in patients starting therapy or when dosage increase is necessary. Analyze lipid panel at intervals of 4 weeks or more.

Pregnancy Risk Factor

X

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. 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.

Use of lovastatin is contraindicated in pregnancy. HMG-CoA reductase inhibitors should be discontinued prior to pregnancy (ADA 2013). If treatment of dyslipidemias is needed in pregnant women or in women of reproductive age, other agents are preferred (Berglund 2012; Stone 2013). The manufacturer recommends administration to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, back pain, or flu-like symptoms. Have patient report immediately to prescriber paresthesia, urinary retention, oliguria, signs of severe muscle problems, or signs of hepatic impairment (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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