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Atorvastatin

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

Medically reviewed by Drugs.com on Jul 26, 2021. Written by ASHP.

Warning

Special Alerts:

[Posted 07/20/2021]

AUDIENCE: Patient, Health Professional, OBGYN, Cardiology, Endocrinology, Pharmacy

ISSUE: The FDA is requesting revisions to the information about use in pregnancy in the prescribing information of the entire class of statin medicines. These changes include removing the contraindication against using these medicines in all pregnant patients. A contraindication is FDA's strongest warning and is only added when a medicine should not be used because the risk clearly outweighs any possible benefit. Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.

FDA expects removing the contraindication will enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke. This includes patients with homozygous familial hypercholesterolemia and those who have previously had a heart attack or stroke.

BACKGROUND: Statins are a class of prescription medicines that have been used for decades to lower low-density lipoprotein (LDL-C or “bad”) cholesterol in the blood. Medicines in the statin class include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.

RECOMMENDATIONS:

  • Patients: Patients taking statins should notify their health care professionals if they become pregnant or suspect they are pregnant. Your health care professional will be able to advise whether you should stop taking the medicine during pregnancy and whether you may stop your statin temporarily while breastfeeding. Patients who are at high risk of heart attack or stroke who require statins after giving birth should not breastfeed and should use alternatives such as infant formula.

  • Health Care Professionals: Health care professionals should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy. Discuss with patients whether they may discontinue statins temporarily while breastfeeding. Advise those who require a statin because of their cardiovascular risk that breastfeeding is not recommended because the medicine may pass into breast milk

The FDA hopes the revised language in the prescribing information will help reassure health care professionals that statins are safe to prescribe in patients who can become pregnant, and help them reassure patients with unintended statin exposure in early pregnancy or before pregnancy is recognized that the medicine is unlikely to harm the unborn baby.

For more information visit the FDA website at: [Web] and [Web].

Introduction

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

Uses for Atorvastatin

Reduction in Risk of Cardiovascular Events

Adjunct to diet and 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.

Adjunct to diet and lifestyle modifications 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.

Adjunct to diet and lifestyle modifications 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.

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.

Extensive evidence demonstrates that statins can substantially reduce LDL-cholesterol concentrations and associated risk of atherosclerotic cardiovascular disease (ASCVD); may be used for secondary prevention or primary prevention in high-risk patients.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of ASCVD risk reduction. Patients with established ASCVD or high risk of ASCVD should also be treated with a statin.

Because relative ASCVD risk reduction is correlated with degree of LDL-cholesterol lowering, use maximum tolerated intensity of a statin to achieve greatest benefit. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is recommended; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%). AHA/ACC considers atorvastatin 40–80 mg daily to be a high-intensity statin and atorvastatin 10–20 mg daily to be a moderate-intensity statin.

The addition of a nonstatin drug (e.g., ezetimibe, PCSK9 inhibitor) to statin therapy may be considered in certain high-risk patients who require further reduction in LDL-cholesterol concentrations, particularly if there is evidence from randomized controlled studies suggesting that the addition of the nonstatin drug further reduces ASCVD events.

When considering whether to initiate statin therapy for primary prevention, AHA/ACC recommends an individualized approach and shared decision making between patient and clinician. According to the guidelines, statin therapy may be considered in certain high-risk groups such as adults 20–75 years of age with LDL cholesterol ≥190 mg/dL, adults 40–75 years of age with diabetes mellitus, adults 40–75 years of age without diabetes mellitus but with LDL-cholesterol levels ≥70 mg/dL and an estimated 10-year ASCVD risk ≥7.5%, and adults 40–75 years of age with chronic kidney disease (not treated with dialysis or transplantation) and LDL-cholesterol concentrations of 70–189 mg/dL who have a 10-year ASCVD risk ≥7.5%.

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). May use in combination with ezetimibe for additive antilipemic effects. 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.

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.

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

Adjunct to nondrug therapies (e.g., dietary management) for the management of elevated serum triglyceride concentrations (Fredrickson type IV).

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. May use in combination with ezetimibe for additive antilipemic effects.

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

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

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

Atorvastatin Dosage and Administration

General

Monitoring during Antilipemic Therapy

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

  • Periodically reinforce adherence to lifestyle modifications. Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of ASCVD.

Administration

Oral Administration

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

Dosage

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

Dosage modifications may be necessary when used concomitantly with certain drugs (see Specific Drugs and Foods under Interactions).

Pediatric Patients

Dyslipidemias
Heterozygous Familial Hypercholesterolemia
Oral

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

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.

Adults

Reduction in Risk of Cardiovascular Events
Oral

Use maximally tolerated statin intensity to achieve optimal ASCVD risk reduction. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is preferred; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%).

The AHA/ACC guideline panel considers atorvastatin 40–80 mg daily to be a high-intensity statin and atorvastatin 10–20 mg daily to be a moderate-intensity statin.

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

Initially, 10 or 20 mg once daily.

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

Usual maintenance dosage: 10–80 mg once daily.

Homozygous Familial Hypercholesterolemia
Oral

10–80 mg once daily.

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. 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.

Patients currently receiving either atorvastatin or amlodipine: Use fixed combination to provide additional therapy. Select atorvastatin and amlodipine doses independently.

Patients currently receiving neither atorvastatin nor amlodipine: Use fixed combination to initiate treatment in patients requiring therapy for dyslipidemias and hypertension and/or angina. Select atorvastatin and amlodipine doses independently.

Prescribing Limits

Pediatric Patients

Dyslipidemias
Oral

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

Special Populations

Hepatic Impairment

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

Renal Impairment

Dosage modification not required.

Geriatric Patients

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

Cautions for Atorvastatin

Contraindications

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

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

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

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

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

Administer to women of childbearing age only when they are highly unlikely to conceive and have been informed of the potential hazards. (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.

Musculoskeletal Effects

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

Rhabdomyolysis with acute renal failure secondary to myoglobinuria reported rarely.

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

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

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

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

AHA/ACC recommends measurement of CK levels in patients with severe statin-associated muscle symptoms; however, routine monitoring is not useful.

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

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

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).

Hepatic Effects

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

Fatal and nonfatal hepatic failure reported rarely.

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage ). Serious statin-related liver injury is rare and unpredictable, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury. AHA/ACC cholesterol management guideline states that it is reasonable to obtain liver function tests in patients with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera); however, routine monitoring not recommended.

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

Hyperglycemic Effects

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

AHA/ACC cholesterol management guideline states that in patients with increased risk of diabetes mellitus or new-onset diabetes mellitus, statin therapy and lifestyle modifications should be continued to reduce risk of ASCVD.

Endogenous Steroid Production

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

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

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).

Cognitive Impairment

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

Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy). Not associated with fixed or progressive dementia (e.g., Alzheimer’s disease) or clinically important cognitive decline. Not associated with any specific statin, patient's age, statin dosage, or concomitant drug therapy.

FDA states that cardiovascular benefits of statins outweigh the small increased risk of cognitive impairment.

If manifestations consistent with cognitive impairment occur, National Lipid Association (NLA) statin safety assessment task force recommends evaluating and managing patients appropriately.

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. Risk is increased in patients with history of hemorrhagic or lacunar stroke.

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. Diabetes also reported more frequently in such patients receiving high-dose atorvastatin.

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.

Use of Fixed Combinations

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

Specific Populations

Pregnancy

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

Lactation

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

Pediatric Use

Safety and efficacy not established in prepubertal children or in children <10 years of age. Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.

Safety and efficacy of atorvastatin in fixed combination with amlodipine not established in children.

Geriatric Use

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

Use with caution, since age ≥65 years is a predisposing factor for myopathy.

Patients >75 years of age may have a higher risk of adverse effects and lower adherence to therapy; consider expected benefits versus adverse effects before initiating statin therapy in this population.

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

Hepatic Impairment

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

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

Renal Impairment

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

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.

Common Adverse Effects

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

Interactions for Atorvastatin

Metabolized by CYP3A4; does not inhibit CYP3A4.

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

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. Carefully monitor for unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage of either drug. (See Specific Drugs and Foods under Interactions.)

Inducers of CYP3A4: Potential pharmacokinetic interaction (variable reductions in plasma atorvastatin concentrations). (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).

Specific Drugs and Foods

Drug

Interaction

Comments

Amlodipine

Modest increase in atorvastatin exposure

Not clinically relevant

Antacids

Decreased plasma atorvastatin concentrations

Antifungals, azoles

Increased risk of myopathy or rhabdomyolysis

Itraconazole: Increased atorvastatin peak plasma concentration and AUC

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 drug

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

Bile acid sequestrants

Additive cholesterol-lowering effects

Decreased absorption of atorvastatin

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

Colchicine

Myopathy, including rhabdomyolysis, reported

Use concomitantly with caution

Cyclosporine

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

Avoid concomitant use

Digoxin

Increased plasma digoxin concentrations

Monitor appropriately

Efavirenz

Possible variable reductions in plasma atorvastatin concentrations

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

Increased risk of myopathy

Fenofibrate: Slight increase in atorvastatin AUC

Gemfibrozil: Increased atorvastatin AUC

Gemfibrozil: Avoid concomitant use

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 drug

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 juice

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

HCV antivirals

Glecaprevir and pibrentasvir: Plasma concentrations of atorvastatin increased by 8.3-fold

Elbasvir and grazoprevir: Plasma concentrations of atorvastatin increased by 1.9-fold

Glecaprevir and pibrentasvir: Concomitant use not recommended

Elbasvir and grazoprevir: Do not exceed atorvastatin dosage of 20 mg daily

HIV protease inhibitors

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

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 drug

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 daily

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

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

Ritonavir-boosted tipranavir: Avoid concomitant use

Letermovir

Increased exposure of atorvastatin; magnitude of interaction may be greater when letermovir is coadministered with cyclosporine

Do not exceed atorvastatin dosage of 20 mg daily

Use of atorvastatin not recommended in patients receiving both letermovir and cyclosporine

Lomitapide

Increased peak plasma concentration and AUC of atorvastatin acid

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

Macrolides (i.e., clarithromycin, erythromycin)

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

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 drug

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

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

Niacin (antilipemic dosages [≥1 g daily])

Increased risk of myopathy

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)

Weigh benefits against risks of concomitant use

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 drug

Omega-3-acid ethyl esters

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

Oral contraceptives

Increased peak plasma concentrations and AUC of ethinyl estradiol and norethindrone

Caution when selecting an oral contraceptive

Rifampin

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

Administer simultaneously

Warfarin

No clinically important effect on PT

Some experts recommend closer monitoring of INR when statin therapy is initiated or adjusted

Atorvastatin Pharmacokinetics

Absorption

Bioavailability

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

Peak plasma concentrations attained at 1–2 hours.

Absolute bioavailability is approximately 14%.

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

Onset

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

Food

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

Special Populations

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

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

Distribution

Extent

Statins are distributed mainly to the liver.

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

Plasma Protein Binding

≥98% (principally albumin).

Elimination

Metabolism

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

Elimination Route

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

Half-life

Approximately 14 hours.

Stability

Storage

Oral

Tablets

Atorvastatin: 20–25°C.

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

Actions

  • Selectively and competitively inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis. 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.

  • 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.

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

  • Risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages or when used concomitantly with certain drugs. 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.

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

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

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

  • 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.

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

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

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

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)*

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

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

Atorvastatin Calcium and Amlodipine Besylate Tablets

Caduet

Pfizer

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 26, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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