Atorvastatin Calcium

Pronunciation

Class: HMG-CoA Reductase Inhibitors
VA Class: CV350
Molecular Formula: ( C33H34FN2O5)2 • Ca • H2O
CAS Number: 134523-03-8
Brands: Caduet, Lipitor

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).1 18

Uses for Atorvastatin Calcium

Prevention of Cardiovascular Events

ACC/AHA cholesterol management guideline recommends statins as first-line therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in adults; atorvastatin may be used for primary or secondary prevention in adults when moderate- or high-intensity statin therapy is indicated.350 (See Prevention of Cardiovascular Events under Dosage and Administration.)

Adjunct to nondrug therapies (lifestyle modifications) in patients without clinical evidence of CHD who have multiple risk factors (e.g., age, smoking, hypertension, low HDL-cholesterol concentrations, family history of early CHD) to reduce the risk of MI, stroke, or angina and the risk of undergoing revascularization procedures.1 350 Consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy for primary prevention.350

Adjunct to nondrug therapies (i.e., lifestyle modifications350 ) in patients without clinical evidence of CHD who have type 2 diabetes mellitus and multiple risk factors (e.g., retinopathy, albuminuria, smoking, hypertension) to reduce the risk of MI or stroke.1 Consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy for primary prevention in such patients.350 Addition of a nonstatin drug (i.e., fenofibrate) to statin therapy in patients with type 2 diabetes mellitus not shown to provide incremental ASCVD risk reduction benefit beyond that provided by statin monotherapy.350 353

Adjunct to nondrug therapies (i.e., lifestyle modifications350 ) in patients with clinical evidence of CHD to reduce the risk of nonfatal MI, fatal and nonfatal stroke, angina, or hospitalization for CHF, and the risk of undergoing revascularization procedures.1 Unless contraindicated, statins are considered first-line therapy in patients 21–75 years of age with clinical ASCVD (i.e., acute coronary syndromes; history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin).350 Addition of a nonstatin drug (i.e., niacin) to statin-based therapy (i.e., simvastatin with or without ezetimibe) in patients with established cardiovascular disease not shown to provide incremental ASCVD risk reduction benefit beyond that provided by statin monotherapy.350 354

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Has been used in patients with CHD to slow the progression of coronary atherosclerosis.67

Intensive antilipemic therapy (atorvastatin 80 mg daily) shown to be more effective than moderate antilipemic therapy (pravastatin 40 mg daily) in reducing the risk of cardiovascular events in patients hospitalized for acute coronary syndrome (16% reduction in composite risk of death or major cardiovascular events for atorvastatin compared with pravastatin regimen).66 Intensive antilipemic therapy also more effective in slowing progression of coronary atherosclerosis in patients with CHD.67

May use in fixed combination with amlodipine when treatment with both atorvastatin (for prevention of cardiovascular events) and amlodipine (for hypertension and/or CAD) is appropriate.65

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

Dyslipidemias

Adjunct to nondrug therapies (e.g., dietary management) in adults to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIa or IIb).1 May use in combination with ezetimibe for additive antilipemic effects.64 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.78 79

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 postmenarchal girls 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

Adjunct to nondrug therapies (e.g., dietary management) for the management of primary dysbetalipoproteinemia (Fredrickson type III).1

Adjunct to nondrug therapies (e.g., dietary management) for the management of elevated serum triglyceride concentrations (Fredrickson type IV).1 However, fibric acid derivatives provide greater benefit in patients with elevated triglyceride concentrations compared with statins.356

Reduction of elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available.1 May use in combination with ezetimibe for additive antilipemic effects.64

Has reduced total and LDL-cholesterol concentrations in patients with hypercholesterolemia associated with or exacerbated by renal transplantation 8 38 39 undergoing use of protease inhibitors.21 37

Has reduced total and LDL-cholesterol concentrations in hypercholesterolemic patients undergoing peritoneal dialysis.34

May use in fixed combination with amlodipine when treatment with both atorvastatin (for dyslipidemias) and amlodipine (for hypertension and/or CAD) is appropriate.65

Atorvastatin Calcium Dosage and Administration

General

  • Patients should be placed on a standard lipid-lowering diet before initiation of atorvastatin therapy and should remain on this diet during treatment with the drug.1 60 63 In patients with CHD or multiple risk factors for CHD, initiate atorvastatin therapy simultaneously with dietary therapy.1

Monitoring during Antilipemic Therapy

  • Manufacturer recommends obtaining lipoprotein concentrations within 2–4 weeks following initiation and/or titration of atorvastatin and adjusting dosage accordingly.1 ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350

  • Periodically reinforce adherence to lifestyle modifications.350

Administration

Oral Administration

Administer orally at any time of day without regard to meals.1 7

Dosage

Available as atorvastatin calcium; dosage expressed in terms of atorvastatin.1 65

Pediatric Patients

Dyslipidemias
Heterozygous Familial Hypercholesterolemia
Oral

Children 10–17 years of age: Initially, 10 mg once daily.1

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed or a daily dosage of 20 mg is reached.1

Adults

Prevention of Cardiovascular Events

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

Although 20 mg once daily is an FDA-labeled dosage, it was not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.350

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

ACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (e.g., atorvastatin 80 mg once daily, or, if not tolerated, atorvastatin 40 mg once daily); if not well tolerated, use maximum tolerated statin intensity.350

Intensify statin therapy to achieve ≥50% reduction in LDL-cholesterol concentrations.350

In patients currently receiving maximum intensity of statin therapy, consider adding a nonstatin drug to further reduce LDL-cholesterol concentrations; however, consider potential benefits, adverse effects, drug interactions, and patient preferences.350

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

ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., atorvastatin 10–20 mg once daily).350

If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (e.g., atorvastatin 80 mg once daily, or, if not tolerated, atorvastatin 40 mg once daily) unless contraindicated.350

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

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

Estimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- to high-intensity statin therapy (e.g., atorvastatin 10–80 mg once daily).350

Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline states may consider moderate-intensity statin therapy (e.g., atorvastatin 10–20 mg once daily).350

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

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

ACC/AHA cholesterol management guideline recommends high-intensity statin therapy (e.g., atorvastatin 80 mg once daily, or, if not tolerated, atorvastatin 40 mg once daily) unless contraindicated.350

In patients currently receiving atorvastatin 40 mg once daily, may increase dosage to 80 mg once daily after evaluating benefits, adverse effects, drug interactions, and patient preferences.350

In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., atorvastatin 10–20 mg once daily) if tolerated.350

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

Dyslipidemias
Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) or Mixed Dyslipidemia
Oral

Initially, 10 or 20 mg once daily.1

Patients who require reductions of >45% in LDL-cholesterol concentration: May initiate therapy with 40 mg once daily.1

Usual maintenance dosage: 10–80 mg once daily.1

Homozygous Familial Hypercholesterolemia
Oral

10–80 mg once daily.1

Atorvastatin/Amlodipine Fixed-combination Tablets (Caduet)
Oral

Patients currently receiving atorvastatin in combination with amlodipine: Use fixed combination as a substitute for the individually titrated drugs.65 Can switch to the fixed-combination preparation containing corresponding individual doses of atorvastatin and amlodipine; alternatively, can increase the dosage of one or both components for additional antihypertensive, antianginal, and/or antilipemic effects.65

Patients currently receiving either atorvastatin or amlodipine: Use fixed combination to provide additional therapy.65 Select initial dosage of the fixed combination based on current dosage of the component being used and the recommended initial dosage for the added monotherapy.65

Patients currently receiving neither atorvastatin nor amlodipine: Use fixed combination to initiate treatment in patients requiring therapy for dyslipidemias and hypertension and/or angina.65 Select initial dosage of fixed combination based on recommended dosages of the individual components.65

Dosage Modification
Oral

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

Prescribing Limits

Pediatric Patients

Dyslipidemias
Oral

Children 10–17 years of age: Maximum 20 mg daily.1

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 (See Hepatic Impairment under Cautions and see Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage modification not required.1

Geriatric Patients

No specific dosage recommendations; however, use with caution.1 (See Geriatric Use under Cautions.)

Cautions for Atorvastatin Calcium

Contraindications

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

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

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

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

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

Administer to women of childbearing age only when they are highly unlikely to conceive and have been informed of the potential hazards.1 (See Advice to Patients.) If the patient becomes pregnant while taking the drug, immediately discontinue therapy and apprise patient of the potential fetal hazard and the lack of known clinical benefit with continued use during pregnancy.1

Musculoskeletal Effects

Myopathy (defined as muscle pain or weakness in conjunction with CK [CPK] concentration increases >10 times the ULN) reported occasionally.1

Rhabdomyolysis with acute renal failure secondary to myoglobinuria reported rarely.1

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins.355 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.355

Risk of myopathy or rhabdomyolysis increased in geriatric patients (≥65 years of age) and in patients with uncontrolled hypothyroidism or renal impairment.1

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

May consider periodic monitoring of CK concentrations; however, there is no assurance that such monitoring will prevent severe myopathy.1

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

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

Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked increases in CK concentrations.1

Discontinue therapy if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected.1

Temporarily withhold or discontinue therapy in any patient experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).1

Hepatic Effects

Increases in serum aminotransferase (AST, ALT) concentrations reported.1 Concentrations returned to or near pretreatment levels following dosage reduction or therapy interruption or discontinuance.1 Not associated with jaundice or other clinical manifestations.1

Fatal and nonfatal hepatic failure reported rarely.1

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage201 ).1 Although manufacturer previously recommended more frequent monitoring,76 FDA concluded that serious statin-related liver injury is rare and unpredictable, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.200 ACC/AHA cholesterol management guideline recommends obtaining liver function tests in adults with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera).350 However, NHLBI expert panel on cardiovascular health and risk reduction in children and adolescents strongly recommends routine monitoring of hepatic function in children and adolescents receiving statins.357

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt atorvastatin therapy.1 If an alternate etiology is not found, do not restart atorvastatin.1

Also see Hepatic Impairment under Cautions.

Hyperglycemic Effects

Increases in HbA1c and fasting serum glucose concentrations reported.1 200 Possible increased risk of developing diabetes.200 May need to monitor glucose concentrations following initiation of statin therapy.201

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

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

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

Endogenous Steroid Production

Statins interfere with cholesterol synthesis and theoretically may blunt adrenal and/or gonadal steroid production.1

No effects on basal plasma cortisol concentration or adrenal reserve observed with atorvastatin.1 Effects on male fertility or on pituitary-gonadal axis in premenopausal women not fully established.1

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. ketoconazole, spironolactone, cimetidine).1

Cognitive Impairment

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) reported rarely.1

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

Use in Patients with Recent Stroke or TIA

In hypercholesterolemic patients without clinically evident CHD who had a stroke or TIA within the past 1–6 months, long-term (median of 4.9 years) therapy with high-dose atorvastatin (80 mg daily) associated with higher incidence of hemorrhagic stroke compared with placebo.1 73 Risk is increased in patients with history of hemorrhagic or lacunar stroke.1 75

Increases in aminotransferase or CK concentrations (≥3 or >10 times the ULN, respectively) reported more frequently in such patients receiving high-dose atorvastatin compared with placebo.1 Diabetes also reported more frequently in such patients receiving high-dose atorvastatin.1

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

Use of Fixed Combinations

When used in fixed combination with amlodipine, consider cautions, precautions, contraindications, and interactions associated with amlodipine.65

Specific Populations

Pregnancy

Category X.1 65 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Distributed into milk in rats; may distribute into milk in humans.1 Use is contraindicated in nursing women; women who require atorvastatin therapy should not breast-feed their infants.1

Pediatric Use

Safety and efficacy not established in prepubertal children or in children <10 years of age.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 atorvastatin in fixed combination with amlodipine not established in children.65

Geriatric Use

No overall differences in efficacy or safety relative to younger adults, but increased sensitivity cannot be ruled out.1 (See Special Populations under Pharmacokinetics.)

Use with caution, since age ≥65 years is a predisposing factor for myopathy.1 In patients >75 years of age, consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

Safety and efficacy of atorvastatin in fixed combination with amlodipine not established in geriatric patients.65

Hepatic Impairment

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

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

Renal Impairment

Dosage modification not necessary in patients with renal impairment.1 However, monitor more closely for adverse musculoskeletal effects, since history of renal impairment may be a risk factor for development of rhabdomyolysis.1

Safety and efficacy not established in patients with end-stage renal disease (ESRD); hemodialysis not expected to substantially enhance clearance since atorvastatin is extensively bound to plasma proteins.1

Common Adverse Effects

Nasopharyngitis, arthralgia, diarrhea, pain in extremity, urinary tract infection, dyspepsia, nausea, musculoskeletal pain, muscle spasms, myalgia, insomnia, pharyngolaryngeal pain.1

Interactions for Atorvastatin Calcium

Metabolized by CYP3A4; does not inhibit CYP3A4.1

When used in fixed combination with amlodipine, consider interactions associated with amlodipine.65 No formal drug interaction studies to date with fixed-combination preparation.65

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (variable increases in plasma atorvastatin concentrations); increased risk of myopathy or rhabdomyolysis.1 Carefully monitor for unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage of either drug.1 (See Specific Drugs and Foods under Interactions.)

Inducers of CYP3A4: Potential pharmacokinetic interaction (variable reductions in plasma atorvastatin concentrations).1 (See Specific Drugs and Foods under Interactions.)

Drugs Transported by Organic Anion Transport Polypeptide 1B1

Inhibitors of organic anion transport polypeptide (OATP) 1B1: Potential pharmacokinetic interaction (increased bioavailability of atorvastatin).1

Specific Drugs and Foods

Drug

Interaction

Comments

Amlodipine

Modest increase in atorvastatin exposure1

Not clinically relevant1

Antacids

Decreased plasma atorvastatin concentrations1

Antifungals, azoles

Increased risk of myopathy or rhabdomyolysis1

Itraconazole: Increased atorvastatin peak plasma concentration and AUC1

Weigh benefits against risks of concomitant use; carefully monitor for muscle pain, tenderness, or weakness, particularly during initial months of therapy and following an increase in dosage of either drug1

Itraconazole: Use lowest necessary dosage of atorvastatin; do not exceed atorvastatin dosage of 20 mg daily1

Bile acid sequestrants

Additive cholesterol-lowering effects20

Decreased absorption of atorvastatin63

Administer statins 1 hour before or 4 hours after the bile acid sequestrant63

Colchicine

Myopathy, including rhabdomyolysis, reported1

Use concomitantly with caution1

Cyclosporine

Increased atorvastatin peak plasma concentration and AUC; increased risk of myopathy or rhabdomyolysis1

Avoid concomitant use1

Digoxin

Increased plasma digoxin concentrations1

Monitor appropriately1

Efavirenz

Possible variable reductions in plasma atorvastatin concentrations1

Fibric acid derivatives (e.g., fenofibrate, gemfibrozil)

Increased risk of myopathy1

Fenofibrate: Slight increase in atorvastatin AUC72

Gemfibrozil: Increased atorvastatin AUC1

Gemfibrozil: Avoid concomitant use1

Other fibric acid derivatives (e.g., fenofibrate): Use concomitantly with caution and only if benefits outweigh risks; consider lower initial and maintenance dosages of atorvastatin (i.e., low- or moderate-intensity statin therapy); carefully monitor for muscle pain, tenderness, or weakness, particularly during initial months of therapy and following an increase in dosage of either drug1 350

Grapefruit juice

Increased atorvastatin peak plasma concentration and AUC; more substantial increases in atorvastatin peak plasma concentration and/or AUC following ingestion of large quantities (≥750–1200 mL daily) of grapefruit juice1

Ingestion of large quantities (>1 L daily) of grapefruit juice may increase risk of myopathy1

HCV protease inhibitors (boceprevir, telaprevir)

Boceprevir: Increased atorvastatin peak plasma concentration and AUC355

Telaprevir: Increased atorvastatin peak plasma concentration and AUC; increased risk of myopathy or rhabdomyolysis1

Boceprevir: Use lowest necessary dosage of atorvastatin; do not exceed atorvastatin dosage of 40 mg daily77 355

Telaprevir: Avoid concomitant use1

HIV protease inhibitors

Increased atorvastatin peak plasma concentration and AUC; increased risk of myopathy or rhabdomyolysis1

Weigh benefits against risks of concomitant use; carefully monitor for unexplained muscle pain, tenderness, or weakness, particularly during initial months of therapy and following an increase in dosage of either drug1

Ritonavir-boosted darunavir, fosamprenavir or ritonavir-boosted fosamprenavir, or ritonavir-boosted saquinavir: Use concomitantly with caution; use lowest necessary dosage of atorvastatin; do not exceed atorvastatin dosage of 20 mg daily1

Lopinavir/ritonavir: Use concomitantly with caution; use lowest necessary dosage of atorvastatin1

Nelfinavir: Monitor closely;355 use lowest necessary dosage of atorvastatin and do not exceed atorvastatin dosage of 40 mg daily1

Ritonavir-boosted tipranavir: Avoid concomitant use1

Lomitapide

Increased peak plasma concentration and AUC of atorvastatin acid374

Adjustment of atorvastatin dosage not required; however, do not exceed lomitapide dosage of 30 mg daily374

Macrolides (i.e., clarithromycin, erythromycin)

Clarithromycin, erythromycin: Increased atorvastatin peak plasma concentration and AUC; increased risk of myopathy or rhabdomyolysis1

Weigh benefits against risks of concomitant use; carefully monitor for unexplained muscle pain, tenderness, or weakness, particularly during initial months of therapy and following an increase in dosage of either drug1

Clarithromycin: Use concomitantly with caution; use lowest necessary dosage of atorvastatin; do not exceed atorvastatin dosage of 20 mg daily1

Erythromycin: Use concomitantly with caution; consider using lower initial and maintenance dosages of atorvastatin1

Niacin (antilipemic dosages [≥1 g daily])

Increased risk of myopathy1

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

Weigh benefits against risks of concomitant use1

Use concomitantly with caution; consider using lower initial and maintenance dosages of atorvastatin; carefully monitor patients for unexplained muscle pain, tenderness, or weakness, particularly during initial months of atorvastatin therapy or following an increase in dosage of either drug1

Omega-3-acid ethyl esters

No effect on rate or extent of exposure to atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin at steady state373

Oral contraceptives

Increased peak plasma concentrations and AUC of ethinyl estradiol and norethindrone1

Caution when selecting an oral contraceptive1

Rifampin

Variable effects on plasma atorvastatin concentrations;2 because delayed administration of atorvastatin following administration of rifampin associated with substantial reductions in plasma atorvastatin concentrations1

Administer simultaneously

Warfarin

No clinically important effect on PT1

Atorvastatin Calcium Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver.1

Peak plasma concentrations attained at 1–2 hours.1

Absolute bioavailability is approximately 14%.1

Evening administration associated with a decrease in the extent of absorption;1 however, antilipemic activity remains unchanged.1

Onset

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

Food

Food decreases rate and extent of absorption but does not alter antilipemic effects.1

Special Populations

Hepatic impairment (Child-Pugh class A and B) or alcoholic liver disease: Substantially increased concentrations.1

Geriatric patients: Peak plasma concentration and AUC are 40 and 30% higher, respectively, in geriatric individuals (≥65 years of age) compared with younger adults.1

Distribution

Extent

Statins are distributed mainly to the liver.

Distributes into milk in rats; may distribute into human milk.1

Plasma Protein Binding

≥98% (principally albumin).1

Elimination

Metabolism

Extensively metabolized in the liver,1 mainly by CYP3A4,1 to active metabolites.1

Elimination Route

Excreted principally in feces; <2% of a dose excreted in urine.1

Half-life

Approximately 14 hours.1

Stability

Storage

Oral

Tablets

Atorvastatin: 20–25°C.1

Atorvastatin/amlodipine fixed combination: 25°C (may be exposed to 15–30°C).65

Actions

  • Selectively and competitively inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.1 Reduces serum concentrations of total cholesterol, LDL-cholesterol, apo B, triglycerides, VLDL-cholesterol, IDL-cholesterol, and non-HDL-cholesterol, and increases serum concentrations of HDL-cholesterol and apolipoprotein A-1.1

  • Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries; modulate BP in hypercholesterolemic patients with hypertension; and possess anti-inflammatory activity.

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.1 350

  • Importance of periodic monitoring of lipoprotein profile to determine goal attainment.1

  • Risk of myopathy and/or rhabdomyolysis.1 Importance of patients promptly reporting any unexplained and/or persistent muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, or if manifestations persist after discontinuance of therapy.1 355

  • Risk of adverse hepatic effects.1 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).1

  • Risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).1 200

  • Risk of increased glucose concentrations and development of type 2 diabetes;1 200 may need to monitor glucose concentrations following initiation of statin therapy.201

  • Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) during therapy and informing pregnant women of risk to fetus.1

  • Importance of avoiding breast-feeding during therapy.1 If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.1

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

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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

Atorvastatin Calcium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg (of atorvastatin)*

Atorvastatin Calcium Tablets

Lipitor

Pfizer

20 mg (of atorvastatin)*

Atorvastatin Calcium Tablets

Lipitor

Pfizer

40 mg (of atorvastatin)*

Atorvastatin Calcium Tablets

Lipitor

Pfizer

80 mg (of atorvastatin)*

Atorvastatin Calcium Tablets

Lipitor

Pfizer

Atorvastatin Calcium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg (of atorvastatin) with Amlodipine Besylate 2.5 mg (of amlodipine)

Caduet

Pfizer

10 mg (of atorvastatin) with Amlodipine Besylate 5 mg (of amlodipine)

Caduet

Pfizer

10 mg (of atorvastatin) with Amlodipine Besylate 10 mg (of amlodipine)

Caduet

Pfizer

20 mg (of atorvastatin) with Amlodipine Besylate 2.5 mg (of amlodipine)

Caduet

Pfizer

20 mg (of atorvastatin) with Amlodipine Besylate 5 mg (of amlodipine)

Caduet

Pfizer

20 mg (of atorvastatin) with Amlodipine Besylate 10 mg (of amlodipine)

Caduet

Pfizer

40 mg (of atorvastatin) with Amlodipine Besylate 2.5 mg (of amlodipine)

Caduet

Pfizer

40 mg (of atorvastatin) with Amlodipine Besylate 5 mg (of amlodipine)

Caduet

Pfizer

40 mg (of atorvastatin) with Amlodipine Besylate 10 mg (of amlodipine)

Caduet

Pfizer

80 mg (of atorvastatin) with Amlodipine Besylate 5 mg (of amlodipine)

Caduet

Pfizer

80 mg (of atorvastatin) with Amlodipine Besylate 10 mg (of amlodipine)

Caduet

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 12/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Amlodipine-Atorvastatin 10-10MG Tablets (RANBAXY PHARMACEUTICALS): 30/$140.00 or 90/$395.96

Amlodipine-Atorvastatin 10-20MG Tablets (RANBAXY PHARMACEUTICALS): 30/$169.99 or 90/$479.95

Amlodipine-Atorvastatin 10-40MG Tablets (RANBAXY PHARMACEUTICALS): 30/$159.98 or 90/$459.98

Amlodipine-Atorvastatin 5-10MG Tablets (RANBAXY PHARMACEUTICALS): 30/$140.00 or 90/$395.96

Amlodipine-Atorvastatin 5-20MG Tablets (RANBAXY PHARMACEUTICALS): 30/$169.99 or 90/$479.95

Amlodipine-Atorvastatin 5-40MG Tablets (RANBAXY PHARMACEUTICALS): 30/$180.00 or 90/$479.95

Atorvastatin Calcium 10MG Tablets (WATSON LABS): 30/$99.99 or 90/$275.96

Atorvastatin Calcium 20MG Tablets (WATSON LABS): 30/$129.99 or 90/$359.98

Atorvastatin Calcium 40MG Tablets (WATSON LABS): 30/$129.99 or 90/$359.98

Atorvastatin Calcium 80MG Tablets (WATSON LABS): 30/$129.99 or 90/$359.98

Caduet 10-10MG Tablets (PFIZER U.S.): 30/$167.98 or 90/$474.95

Caduet 10-20MG Tablets (PFIZER U.S.): 30/$226.99 or 90/$654.96

Caduet 10-40MG Tablets (PFIZER U.S.): 30/$227.98 or 90/$651.99

Caduet 10-80MG Tablets (PFIZER U.S.): 30/$227.89 or 90/$620.05

Caduet 2.5-10MG Tablets (PFIZER U.S.): 30/$162.45 or 90/$470.56

Caduet 2.5-20MG Tablets (PFIZER U.S.): 30/$226.00 or 90/$635.99

Caduet 2.5-40MG Tablets (PFIZER U.S.): 30/$227.98 or 90/$639.99

Caduet 5-10MG Tablets (PFIZER U.S.): 30/$162.99 or 90/$458.96

Caduet 5-20MG Tablets (PFIZER U.S.): 30/$224.00 or 90/$636.95

Caduet 5-40MG Tablets (PFIZER U.S.): 30/$218.00 or 90/$621.98

Caduet 5-80MG Tablets (PFIZER U.S.): 30/$227.98 or 90/$650.96

Lipitor 10MG Tablets (PFIZER U.S.): 30/$119.99 or 90/$336.97

Lipitor 20MG Tablets (PFIZER U.S.): 30/$164.99 or 90/$478.97

Lipitor 40MG Tablets (PFIZER U.S.): 30/$166.99 or 90/$482.97

Lipitor 80MG Tablets (PFIZER U.S.): 30/$164.99 or 90/$474.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 24, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

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