Atorvastatin Calcium Monograph for Professionals - Drugs.com

Brand names: Atorvaliq, Lipitor
Drug class: HMG-CoA Reductase Inhibitors

• Introduction
• Uses
• Dosage
• Warnings
• Interactions
• Stability
• FAQ

Introduction

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

Uses for Atorvastatin Calcium

Reduction in Risk of Cardiovascular Events

Adjunct to diet and lifestyle modifications in adults without clinical evidence of coronary heart disease (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 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 congestive heart failure (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 coronary artery disease) 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 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 (CKD) (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 diet in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) to reduce LDL-cholesterol. May use in combination with ezetimibe for additive antilipemic effects.

Adjunct to diet to decrease elevated LDL-cholesterol in the management of HeFH in males and postmenarchal females 10–17 years of age.

Adjunct to diet for the treatment of adults with primary dysbetalipoproteinemia.

Adjunct to diet in the treatment of adults with hypertriglyceridemia.

Reduction of elevated serum total and LDL-cholesterol concentrations in adult and pediatric patients ≥10 years of age with homozygous familial hypercholesterolemia (HoFH) 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.

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

Atorvastatin Calcium Dosage and Administration

General

Pretreatment Screening

• Obtain baseline liver enzyme tests (e.g., AST, ALT).

• Obtain baseline hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain baseline fasting lipid panel.

Patient Monitoring

• Perform fasting lipid panel periodically 4–12 weeks after statin initiation or dose adjustment; 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.

• Perform repeat liver function tests (e.g., AST, ALT, total bilirubin, alkaline phosphatase) when clinically indicated (i.e., symptoms suggesting hepatotoxicity); routine monitoring in the absence of symptoms is not recommended.

• Monitor hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain creatine kinase (CK) levels in patients with severe statin-associated muscle weakness; routine monitoring in the absence of symptoms is not recommended.

Administration

Oral Administration

Administer orally at the same time each day (at any time of day) without regard to meals.

Atorvastatin oral suspension:Administer oral suspension on an empty stomach (1 hour before or 2 hours after a meal). Shake the bottle well before measuring the dose. Measure oral suspension using a calibrated oral syringe or other oral dosing device scored using metric units of measurements (i.e., mL).

Atorvastatin oral tablets: Administer with or without food.

Atorvastatin and amlodipine fixed-combination tablets: Administer with or without food. Do not break tablets.

If a dose is missed, administer missed dose as soon as possible. If the dose was missed by more than 12 hours, do not administer the missed dose; resume medication with the next scheduled dose.

Dosage

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

LDL-cholesterol-based dosage adjustment occurs ≥4 weeks after initiation and/or titration.

Pediatric Patients

Dyslipidemias

Heterozygous Familial Hypercholesterolemia

Oral

Children ≥10 years of age: Initially, 10 mg once daily. Dosage range is 10–20 mg once daily.

Homozygous Familial Hypercholesterolemia

Oral

Children ≥10 years of age: Initially, 10–20 mg once daily. Dosage range is 10–80 mg once daily.

Adults

Reduction in Risk of Cardiovascular Events

Oral

Initially, 10–20 mg once daily. Dosage range is 10–80 mg once daily.

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%).

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, 10–20 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 and generic equivalents)

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 antilipemic, antianginal, and/or antihypertensive effects. Maximum dosage of atorvastatin or amlodipine in the fixed-combination preparation is 80 or 10 mg daily, respectively.

Dosage Modification for Concomitant Therapy

Saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir:Maximum atorvastatin dosage: 20 mg once daily.

Nelfinavir: Maximum atorvastatin dosage: 40 mg once daily.

Clarithromycin: Maximum atorvastatin dosage: 20 mg once daily.

Itraconazole: Maximum atorvastatin dosage: 20 mg once daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations. Contraindicated in patients with acute liver failure or decompensated cirrhosis. Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.

Renal Impairment

Dosage modification not required. Monitor for development of myopathy.

Geriatric Patients

No specific dosage recommendations; however, use with caution.

Pharmacogenomic Considerations

SLCO1B1 decreased or possible decreased function phenotype: Initial dosage ≤40 mg once daily recommmended.

SLCO1B1 poor function phenotype: Initial dosage ≤20 mg once daily recommmended.

Cautions for Atorvastatin Calcium

Contraindications

• Acute liver failure or decompensated cirrhosis.

• Known hypersensitivity to atorvastatin or any component in the formulation. Anaphylaxis, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported.

• Atorvastatin and amlodipine fixed-combination tablets: Pregnancy, lactation, and active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.

Warnings/Precautions

Musculoskeletal Effects

Myopathy (defined as muscle pain, tenderness, or weakness in conjunction with CK concentration increases) reported.

Rhabdomyolysis with acute renal failure secondary to myoglobinuria reported; rare fatalities have occurred.

Risk of myopathy or rhabdomyolysis increased in geriatric patients (≥65 years of age), in patients with uncontrolled hypothyroidism or renal impairment, and those receving a higher dosage.

Certain drug or food interactions also may increase risk of myopathy and/or rhabdomyolysis.

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

Discontinue therapy if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected. Muscle symptoms and CK elevations may resolve following discontinuance.

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., sepsis; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).

Immune-Mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins. Recurrence reported when the same or a different statin was administered.

Characterized by proximal muscle weakness and elevated CK concentrations that persist despite discontinuance of statin therapy, positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement following therapy with immunosuppressive agents.

Additional neuromuscular and serologic testing may be necessary; treatment with immunosuppressive agents may be required.

Discontinue if IMNM suspected.

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.

Fatal and nonfatal hepatic failure reported rarely.

Consider liver enzyme tests before initiation of therapy and as clinically indicated. 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.

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

Hyperglycemic Effects

Increases in HbA_1c and fasting serum glucose concentrations reported. Possible increased risk of developing diabetes.

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.

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. Weigh benefits against potential risks in patients with recent hemorrhagic stroke.

Use of Fixed Combinations

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

Specific Populations

Pregnancy

All statins were previously contraindicated in pregnant females because fetal risk was thought to outweigh any possible benefit. However, the totality of evidence to date indicates limited potential for statins to cause malformations and other adverse embryofetal effects; FDA has therefore requested removal of the contraindication. Most pregnant patients should still discontinue statins because of the possibility of fetal harm; however, some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) may benefit from continued therapy. Consider patient's individual risks and benefits.

Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician; clinician should advise patient on the appropriate course of action.

Increased risk of miscarriage reported in pregnant women exposed to statins; however, not clear whether drug-related or due to other confounding factors.

Lactation

Distributed into milk in rats; may distribute into milk in humans. Use is not recommended in nursing females; females who require atorvastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.

Females and Males of Reproductive Potential

AHA/ACC cholesterol management guideline states females (including adolescents) of childbearing age who are sexually active should be counseled to use a reliable form of contraception.

Pediatric Use

Safety and efficacy not established in children <10 years of age with heterozygous- or homozygous familial hypercholesterolemia, or in children with other types of hyperlipidemia.

Safety and efficacy of atorvastatin in fixed combination with amlodipine not established in children; effect of the amlodipine component on blood pressure in children <6 years of age not known.

Geriatric Use

No overall differences in efficacy or safety relative to younger adults.

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

Select dosage with caution; monitor for increased risk of 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 acute liver failure or decompensated cirrhosis.

Renal Impairment

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

Studies have not been conducted in patients with end-stage renal disease (ESRD); hemodialysis not expected to substantially enhance clearance since atorvastatin is extensively bound to plasma proteins.

Pharmacogenomic Considerations

Genetic variation in the solute carrier organic anion transporter (SLCO) family member (SLCO1B1), ABCG2 (also known as breast cancer resistance protein [BCRP]), and CYP2C9 genes alter systemic exposure to statins, which can increase the risk for statin-associated musculoskeletal symptoms.

In patients with phenotypes that result in increased statin exposure, consider potential for other patient-specific issues that may increase statin exposure (e.g., renal and hepatic function, drug-drug interactions).

Experts state statin therapy should neither be discontinued nor avoided based on SLCO1B1, ABCG2, or CYP2C9 genotype results for patients with an indication for statin therapy.

Patients with solute carrier organic anion transporter SLCO1B1 decreased, possible decreased, or poor function phenotypes will have increased exposure and risk of statin-associated musculoskeletal symptoms. Lower doses or an alternative statin may be required.

Common Adverse Effects

Common adverse effects (≥5%): Nasopharyngitis, arthralgia, diarrhea, pain in extremity, urinary tract infection.

Drug Interactions

Metabolized by CYP3A4.

Substrate of P-gp, BCRP, and organic anion transporter protein (OATP) 1B1/1B3.

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.

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

Drugs Affecting or Affected by Transport Systems

Inhibitors of OATP1B1, OAT1B3, P-gp, and BCRP: Potential pharmacokinetic interaction (increased bioavailability of atorvastatin); increased risk of myopathy or rhabdomyolysis.

Specific Drugs and Foods

Atorvastatin Calcium 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%. Systemic availability of HMG-CoA reductase inhibitory activity approximately 30%.

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

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

Atorvastatin oral suspension: High fat meal decreases AUC and peak plasma concentration; administer on an empty stomach (1 hour before or 2 hours after a meal).

Distribution

Extent

Statins are distributed mainly to the liver.

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

Plasma Protein Binding

≥98%.

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.

Special Populations

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

Renal impairment: No effect on plasma concentrations or antilipemic effect.

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

Pediatric patients: Clearance similar to that of adults when scaled allometrically by body weight.

Females have slightly increased peak plasma concentrations and AUC; not clinically significant.

Stability

Storage

Oral

Suspension

20–25°C; excursions permitted to 15–30°C. Store and dispense in the original bottle. Use within 60 days of first opening the bottle; discard any remainder.

Tablets

Atorvastatin: 20–25°C.

Atorvastatin/amlodipine fixed combination: 25°C (excursions permitted to 15–30°C).

Actions

• Selectively and competitively inhibits HMG-CoA reductase, causing subsequent reductions 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 apo A-1.

• Other favorable (pleiotropic) effects include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, and antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.

Advice to Patients

• Advise patients of the 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.

• Stress importance of periodic monitoring of lipoprotein profile to determine goal attainment.

• Advise patients of the risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages, when consuming large quantities of grapefruit juice, or when used concomitantly with certain drugs. Stress 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.

• Advise patients of the risk of adverse hepatic effects. Stress importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).

• Advise patients of the risk of increased glucose concentrations and development of type 2 diabetes.

• Advise patients that atorvastatin should be administered at the same time each day, at any time of day.

• Advise patients that atorvastatin tablets may be administered with or without food.

• Advise patients that atorvastatin oral suspension should be administered on an empty stomach (1 hour before or 2 hours after a meal). Advise patients to shake the bottle of atorvastatin oral suspension before measuring the dose with a calibrated oral dosing syringe or other oral dosing device scored using metric units of measurements (i.e., mL).

• Advise patients that the fixed-combination preparation containing atorvastatin and amlodipine (Caduetand generic equivalents) should be administered as a whole tablet with or without food at the same time each day, at any time of day. Do not break the tablet before administration.

• If a dose of atorvastatin tablets, oral suspension, or the fixed-combination preparation containing atorvastatin and amlodipine is missed, advise patients to take the missed dose as soon as possible. If it has been more than 12 hours since the missed dose, advise patients to wait and take the dose at the next scheduled time; do not double the next dose.

• Advise females of reproductive potential (including adolescents) of the risk to a fetus and to use effective contraception during treatment. Advise females to contact their clinician if they become pregnant or suspect pregnancy during therapy

• Advise females not to breastfeed during therapy.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

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

AHFS DI Essentials™. © Copyright 2025, Selected Revisions October 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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