Version October 2024
Dosage guidance:
Dosing: Atorvastatin 40 to 80 mg/day is considered a high-intensity statin (generally reduces low-density lipoprotein cholesterol [LDL-C] by ≥50%). Atorvastatin 10 to 20 mg/day is considered a moderate-intensity statin (generally reduces LDL-C by ~30% to 49%). Assess response ~1 to 3 months after initiation of therapy or dose adjustment and every 3 to 12 months thereafter (Ref).
Clinical considerations: Use in conjunction with lifestyle modification (eg, diet, exercise). When initiating therapy and selecting dose intensity, consider age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease risk, risk-enhancing factors, potential adverse effects, and drug interactions (Ref).
Heterozygous familial hypercholesterolemia:
Note: Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
High-intensity therapy: Oral: Initial: 40 or 80 mg once daily; if 40 mg once daily is initiated and tolerated, increase to 80 mg once daily.
Prevention of atherosclerotic cardiovascular disease:
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration based on estimated 10-year ASCVD risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Patients without diabetes, age 40 to 75 years, and LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C >160 mg/dL, statin therapy is usually recommended (Ref).
Moderate-intensity therapy: Oral: 10 to 20 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and an LDL-C >100 mg/dL (Ref).
Moderate-intensity therapy: Oral: 10 to 20 mg once daily to reduce LDL-C by 30% to 49%; higher risk patients with multiple risk-enhancing factors may benefit from higher doses to reduce LDL-C by ≥50% (Ref).
ASCVD 10-year risk ≥20%: High-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Patients with diabetes:
Age 40 to 75 years without additional ASCVD risk factors: Moderate-intensity therapy: Oral: 10 to 20 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD risk ≥7.5% or multiple ASCVD risk factors: High-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Patients with LDL-C ≥190 mg/dL and age 20 to 75 years:
Note: High-intensity therapy indicated regardless of ASCVD risk calculation or coexisting diabetes mellitus.
High-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Secondary prevention in patients with established atherosclerotic cardiovascular disease (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease):
Note: Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk).
High-intensity therapy: Oral: 80 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Transplantation:
Note: Certain immunosuppressive drugs can induce or exacerbate hypercholesterolemia. Significant drug interactions between statins and immunosuppressant drugs are frequent; some interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (Ref). Consult drug interactions database for more detailed information.
Transplantation, post heart (off-label use): Oral: Initial: 10 mg once daily starting 1 to 2 weeks after transplant, regardless of baseline cholesterol levels; increase dose based on response, tolerability, and use of concomitant medications up to 20 mg once daily (Ref).
Transplantation, post kidney (off-label use):
Note: The decision to initiate therapy for primary or secondary prevention is similar to the non-transplant population (see the "Prevention of atherosclerotic cardiovascular disease" indication). However, in patients who are 30 to 39 years of age, some experts suggest statin therapy post-kidney transplantation for primary prevention of ASCVD. For primary prevention of ASCVD in patients 18 to 29 years of age, use shared decision making while considering risks and benefits (Ref).
Oral: Initial: 10 mg once daily; increase dose based on response, tolerability, and use of concomitant medications up to 20 mg once daily (Ref).
Missed doses: Oral suspension: If a dose is missed by >12 hours, omit that dose and administer the next dose at the regularly scheduled time; do not administer extra doses to make up for a missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, Jeong Park, PharmD, MS, BCTXP, FCCP, FAST, Arun Jesudian, MD, Sasan Sakiani, MD.
Note: Although use is contraindicated in patients with active liver failure or decompensated cirrhosis according to the manufacturer's labeling, baseline elevation in AST/ALT should not preclude use of statins for compelling indications in patients with chronic stable liver disease including compensated cirrhosis (Ref).
Hepatic impairment prior to treatment initiation:
Child-Turcotte-Pugh class A: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B: Note: Consider use only when benefit likely outweighs risk (eg, secondary prevention in patients with established atherosclerotic cardiovascular disease, including ischemic stroke, transient ischemic attack, peripheral artery disease) (Ref).
Oral: Initial: 20 mg once daily; maximum recommended dose: 20 mg/day (Ref).
Child-Turcotte-Pugh class C: Use of a hydrophilic statin (eg, rosuvastatin) is recommended. If use of atorvastatin is deemed necessary: Initial: 10 mg once daily; a maximum dose of 10 mg once daily is recommended (Ref).
Acute hepatotoxicity or worsening of hepatic function (eg, progression from Child-Turcotte-Pugh class A to B) during treatment:
Progression from baseline to Child-Turcotte-Pugh class A: Although use is contraindicated in patients with active liver failure or decompensated cirrhosis according to the manufacturer's labeling, if atorvastatin-induced hepatoxicity has been ruled out, may continue atorvastatin therapy with no dosage adjustment necessary (Ref).
Progression to Child-Turcotte-Pugh class B and C: Although use is contraindicated in patients with active liver failure or decompensated cirrhosis according to the manufacturer's labeling, if atorvastatin-induced toxicity (eg, liver injury, rhabdomyolysis) has been ruled out, may continue atorvastatin therapy with no dosage adjustment necessary; however, in patients with decompensated cirrhosis, consider not exceeding 10 mg once daily (Ref). Continued use of statin therapy may be hepatoprotective in patients with decompensated cirrhosis (Ref).
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate creatine kinase level (Ref).
Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of atorvastatin. If muscle symptoms recur, discontinue atorvastatin use. After muscle symptom resolution, may use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Prevention of atherosclerotic cardiovascular disease:
Note: If LDL cholesterol (LDL-C) goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration based on estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Age >75 years: Note: Assess ASCVD risk, life expectancy, and likelihood for adverse effects. Consider moderate-intensity therapy after shared decision-making with patient:
Oral: 10 to 20 mg once daily (Ref).
Secondary prevention in patients with established atherosclerotic cardiovascular disease (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease):
Note: Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (Ref).
Age >75 years: Moderate- to high-intensity therapy: Oral: 10 to 80 mg once daily (Ref); if a moderate-intensity dose (10 to 20 mg once daily) is started and tolerated, increase to a high-intensity dose (40 to 80 mg once daily) within 3 months (Ref).
Refer to adult dosing for other indications.
(For additional information see "Atorvastatin: Pediatric drug information")
Dosage guidance:
Dosing: Dosage should be individualized according to the baseline LDL-C level, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks.
Heterozygous familial and nonfamilial hypercholesterolemia:
Note: Begin treatment if after adequate trial (6 to 12 months) of intensive lifestyle modification emphasizing body weight normalization and diet, the following are present (Ref):
LDL-C ≥190 mg/dL or
LDL-C remains ≥160 mg/dL and 2 or more cardiovascular risk factors: family history of premature atherosclerotic cardiovascular disease (<55 years of age); overweight; obesity; or other elements of insulin resistance syndrome or
LDL-C ≥130 mg/dL and diabetes mellitus (Ref).
Children 6 to <10 years of age (Tanner stage I): Limited data available: Oral: Initial: 5 mg once daily; if target LDL-C not achieved after 4 weeks, may increase incrementally by doubling dose (10 mg/day, 20 mg/day) at monthly intervals until target LDL-C; usual maximum daily dose: 40 mg/day; however, in some cases doses up to 80 mg/day have been used; dosing based on a long-term trial (3 years) of 272 patients (age range: 6 to 15 years); doses of 80 mg/day were used in 12 patients <10 years of age; over the 3 year study duration, similar efficacy was observed without growth or maturation impairment (Ref).
Children and Adolescents 10 to 17 years: Oral: Initial: 10 mg once daily; if target LDL-C not achieved after 4 weeks, may increase incrementally by doubling dose (20 mg/day, 40 mg/day) at monthly intervals until target LDL-C up to a maximum daily dose: 80 mg/day (Ref).
Hyperlipidemia: Limited data available: Children and Adolescents 10 to 17 years (males and postmenarchal females): Oral: Initial: 10 mg once daily; if LDL-C target not achieved after 1 to 3 months, may increase to meet target LDL-C; in pediatric patients with heterozygous familial hypercholesterolemia, a maximum titrated dose based upon LDL response: 80 mg/day was used (Ref).
Transplantation post-heart; prevention of cardiac allograft vasculopathy (CAV): Limited data available:
Note: Initiate following heart transplantation regardless of baseline cholesterol levels in children and adolescents with high risk for rejection and CAV (eg, retransplantation, elevated panel reactive antibodies) (Ref). Significant drug interactions between statins and immunosuppressant drugs are frequent; many interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (Ref); consult drug interactions database for more detailed information.
Children and Adolescents: Oral: 0.2 mg/kg/day rounded to nearest 2.5 mg increment; maximum daily dose: 20 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥10 years and Adolescents: Discontinue use until symptoms can be evaluated; check CPK level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of atorvastatin and retitrate. If muscle symptoms recur, discontinue atorvastatin use. After muscle symptom resolution, may reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Altered kidney function:
Mild to severe impairment: Children ≥10 years and Adolescents: No dosage adjustment necessary.
Hemodialysis, intermittent: There are no recommendations in the manufacturer's labeling (has not been studied); however, atorvastatin is highly protein bound, making it unlikely to be cleared by dialysis. Based on adult experience, it is poorly dialyzed and no dosage adjustment or supplemental dose is recommended (Ref).
Peritoneal dialysis: There are no recommendations for dosing in patients undergoing peritoneal dialysis. Based on adult experience, it is poorly dialyzed and no dosage adjustment is necessary (Ref).
Children ≥10 years and Adolescents: Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
Statins are associated with increased serum transaminases and hepatotoxicity (Ref). Asymptomatic transient or persistent increases both <3 or >3 times the ULN in serum transaminases may occur with all statins; the increase in ALT is typically greater than the increase in AST (Ref). Additionally, there are postmarketing reports of fatal and nonfatal hepatic failure, consisting of a cholestatic/mixed pattern (more common with atorvastatin) or hepatocellular pattern (Ref). Drug-induced autoimmune hepatitis has also been documented (Ref).
Upon dose reduction or discontinuation, transaminase levels return to or near pretreatment levels; although, mild elevations resolve with continued use in some cases (Ref). Chronic liver injury (defined as liver biochemical or histological abnormalities that persisted for 6 months or more after onset) has been reported (Ref).
Mechanism: Unclear; inhibition of the CYP450 system, leading to increased plasma concentrations of statins has been postulated, as well as an immune-mediated response (Ref). Changes in the lipid components of the hepatocyte membrane may lead to increased permeability and leakage of liver enzymes (Ref).
Onset: Varied; most cases occur within the first 3 months of initiation or dose escalation (Ref). Duration of atorvastatin prior to development of hepatotoxicity has been reported from ∼1 month to 10 years (Ref).
Risk factors:
• Administration of high oral daily dose of lipophilic drugs that undergo extensive hepatic metabolism, such as atorvastatin, may increase the risk of developing drug-induced liver injury (Ref).
• Concurrent medications with statin drug-drug interactions or hepatotoxic properties (Ref)
• Hepatotoxicity is more commonly associated with atorvastatin than pravastatin, rosuvastatin, and simvastatin (Ref). Fluvastatin is associated with the greatest risk of developing hepatotoxicity (Ref).
• Cross-reactivity between different statins and the susceptibility to hepatotoxicity is unknown, as data have shown conflicting results (Ref).
• Chronic hepatitis B and alcohol consumption are independent risk factors for hepatic aminotransferase elevation associated with statins in patients 80 years of age or older (Ref).
Statins are associated with several muscle-related effects, including:
• Myalgia (muscle symptoms without significant creatine kinase [CK] elevations; also known as statin-associated muscle symptoms) (Ref)
• Myopathy (defined as unexplained muscle pain or weakness accompanied by a CK ≥10 times the ULN) (Ref)
• Rhabdomyolysis (CK >40 times the ULN) (Ref) often with acute renal failure secondary to myoglobinuria (Ref)
• Immune-mediated necrotizing myopathy (IMNM) (elevated CK plus the presence of antibodies against HMG-CoA) (Ref)
Mechanism: Uncertain; alterations in the mevalonate pathway and changes in the electrical and structural characteristics of the sarcolemma related to calcium ion flux possibly contribute (Ref). Decreased ubiquinone, which is essential for energy production in skeletal muscle, may also contribute (Ref). Myopathy/rhabdomyolysis risk is related to circulating active drug concentrations (Ref). IMNM is considered an immune-mediated process; autoantibodies against HMG-CoA reductase (anti-HMG-CoA) have been identified (Ref).
Onset: Delayed; often presents within a few months after starting therapy (highest risk within first year of use), when the dose of the statin is increased, or when introducing an interacting drug (Ref). Muscle symptoms often appear more promptly when patients are reexposed to the same statin (Ref). Duration of statin use prior to development of IMNM is ~2 to 3 years (Ref).
Risk factors:
• First year of therapy (Ref)
• Addition of an interacting drug (eg, concurrent use of strong CYP3A4 inhibitors or medications associated with myopathy [eg, colchicine]) (Ref)
• Older patients (Ref)
• Hypothyroidism (Ref)
• Preexisting muscle disease (Ref)
• Kidney impairment (Ref)
• Females (Ref)
• Low body mass index (Ref)
• Heavy exercise (Ref)
• Surgery (Ref)
• Higher HMG-CoA reductase inhibitory activity (Ref), rosuvastatin > atorvastatin > simvastatin > pravastatin ≈ lovastatin (Ref)
• Although incidence increases with dose for most statins, there was no difference found in incidence with atorvastatin dose (Ref)
• Asian population: Increased plasma concentrations (up to ≈ twofold with atorvastatin) may result in increased risk of myopathy (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%:
Gastrointestinal: Diarrhea (7% to 14%)
Neuromuscular & skeletal: Arthralgia (9% to 12%)
Respiratory: Nasopharyngitis (13%)
1% to 10%:
Endocrine & metabolic: Diabetes mellitus (6%)
Gastrointestinal: Dyspepsia (6%), nausea (7%)
Genitourinary: Urinary tract infection (7% to 8%)
Hepatic: Increased serum transaminases (≤2%) (table 1)
|
Drug (Atorvastatin) |
Placebo |
Dose |
Number of Patients (Atorvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
2% |
N/A |
80 mg |
N/A |
N/A |
|
0.9% |
0.1% |
80 mg |
2,365 |
2,366 |
|
0.6% |
N/A |
40 mg |
N/A |
N/A |
|
0.2% |
N/A |
10 mg |
N/A |
N/A |
|
0.2% |
N/A |
20 mg |
N/A |
N/A |
Nervous system: Insomnia (5%), intracranial hemorrhage (2%)
Neuromuscular & skeletal: Limb pain (3% to 9%) (table 2), muscle spasm (2% to 5%) (table 3), musculoskeletal pain (2% to 5%) (table 4), myalgia (3% to 8%) (table 5)
|
Drug (Atorvastatin) |
Placebo |
Dose |
Number of Patients (Atorvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
9% |
6% |
40 mg |
604 |
7,311 |
|
9% |
6% |
10 mg |
3,908 |
7,311 |
|
4% |
6% |
20 mg |
188 |
7,311 |
|
3% |
6% |
80 mg |
4,055 |
7,311 |
|
Drug (Atorvastatin) |
Placebo |
Dose |
Number of Patients (Atorvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
5% |
3% |
10 mg |
3,908 |
7,311 |
|
5% |
3% |
20 mg |
188 |
7,311 |
|
5% |
3% |
40 mg |
604 |
7,311 |
|
2% |
3% |
80 mg |
4,055 |
7,311 |
|
Drug (Atorvastatin) |
Placebo |
Dose |
Number of Patients (Atorvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
5% |
4% |
40 mg |
604 |
7,311 |
|
5% |
4% |
10 mg |
3,908 |
7,311 |
|
3% |
4% |
20 mg |
188 |
7,311 |
|
2% |
4% |
80 mg |
4,055 |
7,311 |
|
Drug (Atorvastatin) |
Placebo |
Dose |
Number of Patients (Atorvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
8% |
3% |
40 mg |
604 |
7,311 |
|
6% |
3% |
20 mg |
188 |
7,311 |
|
4% |
3% |
10 mg |
3,908 |
7,311 |
|
3% |
3% |
80 mg |
4,055 |
7,311 |
Respiratory: Pharyngolaryngeal pain (3% to 4%)
Frequency not defined:
Gastrointestinal: Abdominal distress, eructation, flatulence
Nervous system: Malaise
Neuromuscular & skeletal: Joint swelling, muscle fatigue, neck pain
Ophthalmic: Blurred vision
Otic: Tinnitus
Respiratory: Epistaxis
Miscellaneous: Fever
Postmarketing:
Dermatologic: Bullous rash, erythema multiforme, exacerbation of psoriasis (Ref), lichenoid eruption (Ref), Stevens-Johnson syndrome, toxic epidermal necrolysis (Ref), urticaria (Ref)
Gastrointestinal: Cholestasis (Ref), pancreatitis (Ref)
Genitourinary: Cystitis (interstitial) (Ref)
Hematologic & oncologic: Immune thrombocytopenia (Ref)
Hepatic: Autoimmune hepatitis (Ref), hepatic failure (Ref), hepatitis (Ref), increased gamma-glutamyl transferase (Ref), increased serum alkaline phosphatase (Ref)
Hypersensitivity: Anaphylaxis, angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref)
Immunologic: Dermatomyositis (Ref)
Infection: Reactivation of HBV (Ref)
Nervous system: Cognitive dysfunction (reversible; including amnesia, confusion, memory impairment) (Ref), depression, dizziness, fatigue, myasthenia (Ref), myasthenia gravis (including exacerbation of myasthenia gravis, ocular myasthenia), nightmares (Ref), peripheral neuropathy
Neuromuscular & skeletal: Immune-mediated necrotizing myopathy (Ref), increased creatine phosphokinase in blood specimen (Ref), myopathy (Ref), myositis (including necrotizing autoimmune myositis) (Ref), rhabdomyolysis (Ref), rupture of tendon (Ref)
Ophthalmic: Diplopia (Ref)
Renal: Acute interstitial nephritis (Ref)
Respiratory: Interstitial lung disease
Hypersensitivity (eg, anaphylaxis, angioneurotic edema, erythema multiforme, Steven Johnson syndrome, toxic epidermal necrolysis) to atorvastatin or any component of the formulation; acute liver failure or decompensated cirrhosis.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent therapy with boceprevir, cyclosporine, elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, simeprevir, telaprevir, or velpatasvir/sofosbuvir.
Concerns related to adverse effects:
• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported.
Disease-related concerns:
• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease; use is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Stroke: Patients with recent stroke or TIA receiving long-term therapy with high-dose (ie, 80 mg/day) atorvastatin may be at increased risk for hemorrhagic stroke (SPARCL Investigators [Amarenco 2006]). A subsequent post-hoc analysis demonstrated that patients with lacunar or hemorrhagic stroke may be at higher risk of hemorrhagic stroke; however, this finding was determined to be hypothesis generating. The overall benefit of treatment with atorvastatin (ie, reduced risk of stroke and cardiovascular events) in this population seems to outweigh the increased risk of hemorrhagic stroke if one truly exists (Goldstein 2008).
Special populations:
• Surgical patients: Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral, as calcium:
Atorvaliq: 20 mg/5 mL (150 mL) [contains ethylparaben, methylparaben, propylparaben]
Tablet, Oral:
Lipitor: 10 mg, 20 mg, 40 mg, 80 mg
Generic: 10 mg, 20 mg, 40 mg, 80 mg
May be product dependent
Suspension (Atorvaliq Oral)
20 mg/5 mL (per mL): $1.44
Tablets (Atorvastatin Calcium Oral)
10 mg (per each): $0.02 - $7.50
20 mg (per each): $0.03 - $10.70
40 mg (per each): $0.04 - $10.70
80 mg (per each): $0.06 - $10.70
Tablets (Lipitor Oral)
10 mg (per each): $15.55
20 mg (per each): $22.18
40 mg (per each): $22.18
80 mg (per each): $22.18
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lipitor: 10 mg, 20 mg, 40 mg, 80 mg [contains polysorbate 80]
Generic: 10 mg, 20 mg, 40 mg, 80 mg
Oral:
Suspension: Administer on an empty stomach, at least 1 hour before or 2 hours after a meal; may take without regard to time of day. Measure dose using a calibrated oral syringe or other oral dosing device containing scored metric units of measurement (eg, mL).
Tablet: Administer with or without food; may take without regard to time of day. The manufacturer's labeling states tablets should not be broken; however, available data do not indicate any safety or efficacy concerns with this practice.
Oral: May be taken without regard to meals or time of day. The manufacturer's labeling states tablets should not be broken; however, available data do not indicate any safety or efficacy concerns with this practice.
Heterozygous familial hypercholesterolemia: To reduce elevated total cholesterol (total-C), LDL cholesterol (LDL-C), apolipoprotein B (apo B), and triglyceride levels, and to increase HDL cholesterol in patients with primary hypercholesterolemia.
Heterozygous familial hypercholesterolemia (pediatrics): To reduce total-C, LDL-C, and apo B levels in pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia with LDL-C ≥190 mg/dL, LDL-C ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD), or LDL-C ≥160 mg/dL with 2 or more other CVD risk factors.
Homozygous familial hypercholesterolemia: To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.
Prevention of atherosclerotic cardiovascular disease:
Primary prevention of atherosclerotic cardiovascular disease (ASCVD): To reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients without a history of coronary heart disease (CHD) but who have multiple CHD risk factors.
Secondary prevention in patients with established ASCVD: To reduce the risk of MI, stroke, revascularization procedures, and angina in patients with a history of CHD.
Transplantation, post heart; Transplantation, post kidney
Atorvastatin is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication for primary prevention of cardiovascular disease in frail older adults ≥85 years of age with an expected life expectancy of < 3 years (O’Mahony 2023).
Atorvastatin may be confused with atomoxetine, lovastatin, nystatin, pitavastatin, pravastatin, rosuvastatin, simvastatin
HMG-CoA reductase inhibitors (when referred to as "statins") may be confused with nystatin.
Lipitor may be confused with labetalol, Levatol, lisinopril, Loniten, Lopid, Mevacor, Zocor, ZyrTEC
Substrate of BCRP/ABCG2, CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Amiodarone: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Asciminib: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Atazanavir: May increase the serum concentration of Atorvastatin. Management: Use of atorvastatin and atazanavir/cobicistat is not recommended. Use the lowest atorvastatin dose necessary and titrate carefully due to the increased risk of statin toxicities. Alternative statins include fluvastatin, pravastatin, and rosuvastatin. Risk D: Consider therapy modification
Belumosudil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider therapy modification
Belumosudil: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of BCRP for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the BCRP substrate may be required. Risk D: Consider therapy modification
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of NTCP Substrates. Management: Coadministration of bulevirtide with sodium taurocholate co-transporting polypeptide (NTCP) substrate should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Ceftobiprole Medocaril: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Cimetidine: May enhance the adverse/toxic effect of Atorvastatin. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Risk C: Monitor therapy
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification
Clarithromycin: May increase the serum concentration of Atorvastatin. Management: Limit atorvastatin to a maximum dose of 20 mg/day when used with clarithromycin. If this combination is used, monitor patients more closely for evidence of atorvastatin toxicity. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Cobicistat: May increase the serum concentration of Atorvastatin. Management: Avoid the combined use of atorvastatin with atazanavir/cobicistat. Atorvastatin dose should not exceed 20 mg daily when combined with other cobicistat-containing regimens. Risk D: Consider therapy modification
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Danazol: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Danicopan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Darunavir: May increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary and limit the atorvastatin dose to 20 mg daily in patients taking darunavir. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Delavirdine: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Digoxin: Atorvastatin may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Elacestrant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Elbasvir and Grazoprevir: May increase the serum concentration of Atorvastatin. Management: Limit the adult dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Use the lowest atorvastatin dose necessary and monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Risk D: Consider therapy modification
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of Atorvastatin. Encorafenib may decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). This applies to atorvastatin, lovastatin and simvastatin. Risk C: Monitor therapy
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosamprenavir: Atorvastatin may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary and limit the atorvastatin dose to 20 mg daily in patients taking fosamprenavir. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Atorvastatin. Management: Avoid large quantities of grapefruit juice (more than 1.2 liters daily) during treatment with atorvastatin. Monitor for atorvastatin adverse effects (eg, myopathy, rhabdomyolysis) in patients who consume smaller quantities or whose intake has changed. Risk D: Consider therapy modification
Indinavir: May increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary and titrate carefully in patients taking indinavir. Monitor patients carefully for signs and symptoms of myopathy and rhabdomyolysis during coadministration. Risk D: Consider therapy modification
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Istradefylline: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Itraconazole: May increase the serum concentration of Atorvastatin. Management: Limit atorvastatin to a maximum adult dose of 20 mg/day in patients receiving itraconazole. Assess clinical response to ensure that the lowest necessary dose of atorvastatin is used. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Risk D: Consider therapy modification
Ketoconazole (Systemic): Atorvastatin may enhance the adverse/toxic effect of Ketoconazole (Systemic). Specifically, there is a theoretical potential for additive effects on reducing endogenous steroid concentrations. Ketoconazole (Systemic) may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Ledipasvir: May enhance the adverse/toxic effect of Atorvastatin. Risk C: Monitor therapy
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Letermovir: May increase the serum concentration of Atorvastatin. Management: Limit the atorvastatin dose to 20 mg daily when combined with letermovir. When letermovir is coadministered with cyclosporine, the use of atorvastatin (at any dose) is not recommended. Risk D: Consider therapy modification
Lomitapide: May increase the serum concentration of Atorvastatin. Atorvastatin may increase the serum concentration of Lomitapide. Management: When the lomitapide dose is 10 mg daily or greater, reduce the lomitapide dose by 50% when combined with atorvastatin. No dose adjustment is required when the lomitapide dose is 5 mg daily. Risk D: Consider therapy modification
Lonafarnib: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Lopinavir: May increase the serum concentration of Atorvastatin. Management: Consider the risks and benefits of this combination. If coadministered, use the lowest dose of atorvastatin necessary and monitor patients for signs and symptoms of myopathy, especially at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Midazolam: Atorvastatin may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Nelfinavir: May increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary in patients taking nelfinavir, and do not exceed atorvastatin 40 mg daily. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Atorvastatin. Management: Consider temporarily discontinuing atorvastatin during treatment with nirmatrelvir/ritonavir. It is not necessary to hold atorvastatin either prior to or after completion of nirmatrelvir/ritonavir treatment. Risk D: Consider therapy modification
Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Oteseconazole: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Posaconazole: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Resmetirom: May increase the serum concentration of Atorvastatin. Management: Do not exceed atorvastatin doses of 40 mg daily during coadministration with resmetirom. Monitor for increased atorvastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider therapy modification
RifAMPin: May increase the serum concentration of Atorvastatin. RifAMPin may decrease the serum concentration of Atorvastatin. Management: Administer atorvastatin and rifampin simultaneously if using both. Monitor atorvastatin response closely. Risk D: Consider therapy modification
Ritonavir: May increase the serum concentration of Atorvastatin. Management: Use lowest atorvastatin dose needed. If ritonavir is combined with another protease inhibitor, see the drug interaction monograph for that protease inhibitor. Risk D: Consider therapy modification
Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Risk C: Monitor therapy
Roxadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor therapy
Sacubitril: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Saquinavir: May increase the serum concentration of Atorvastatin. Management: Limit the atorvastatin dose to 20 mg in patients taking saquinavir and ritonavir. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Simeprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Sofosbuvir: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Sparsentan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
St John's Wort: May decrease serum concentrations of the active metabolite(s) of HMG-CoA Reductase Inhibitors (Statins). Management: Consider avoiding the concomitant administration of St John's Wort with atorvastatin, lovastatin and simvastatin in order to avoid the potential for decreased effects statins. If coadministered, monitor for decreased statin efficacy. Risk D: Consider therapy modification
Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Talazoparib: Atorvastatin may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ticagrelor: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Tipranavir: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Vadadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Velpatasvir: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Verapamil: Atorvastatin may increase the serum concentration of Verapamil. Verapamil may increase the serum concentration of Atorvastatin. Management: Consider using lower doses of atorvastatin when used together with verapamil, and monitor closely for signs of HMG-CoA reductase inhibitor toxicity (eg, myositis, rhabdomyolysis, hepatotoxicity). Risk D: Consider therapy modification
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
Atorvastatin serum concentrations may be increased by grapefruit juice. Management: Avoid concurrent intake of large quantities of grapefruit juice (>1.2 liters/day).
Adequate contraception is recommended if an HMG-CoA reductase inhibitor (statin) is required in patients who may become pregnant (AHA/ACC [Grundy 2019a]; CCS [Pearson 2021]). Patients planning to become pregnant should discuss their lifetime risk of cardiovascular disease, as well as risks and benefits of statin therapy with their health care team (CCS [Pearson 2021]). When appropriate, statins can be discontinued 1 to 2 months prior to conception (AHA/ACC [Grundy 2019a]).
When a statin is needed in a patient of reproductive potential, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred to limit placental transfer (CCS [Pearson 2021]).
In healthy pregnancies, changes in lipid synthesis occur that are required for normal placental and fetal growth. Low-density lipoprotein cholesterol and triglycerides increase as pregnancy progresses and decline postpartum. HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Therefore, based on the mechanism of action, in utero exposure may cause fetal harm (Lecarpentier 2012); however, data from available studies have not shown an increased risk of major congenital anomalies following first trimester exposure (Bateman 2015; Chang 2021; Vahedian-Azimi 2021a). Additional data are needed to evaluate other pregnancy outcomes, such as miscarriage (Vahedian-Azimi 2021b).
Because there is potential for fetal harm, statins should be discontinued once pregnancy is recognized (AHA/ACC [Grundy 2019a]; Brunham 2018). If lipid-lowering therapy during pregnancy is required, it should be individualized based on the therapeutic needs of the patient, considering the lifetime risk of untreated disease, use of nonstatin therapies, as well as the known risks and benefits of statins. Based on limited data, when a statin is needed in a pregnant patient, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred. Lipophilic statins (eg, atorvastatin, fluvastatin, lovastatin, simvastatin, pitavastatin) may be more likely to cross the placenta and increase the risk of congenital malformations (AHA/ACC [Grundy 2019a]; CCS [Pearson 2021]; Lecarpentier 2012).
Additional data are needed to clarify the role of statins for the prevention of atherosclerotic cardiovascular disease in at-risk pregnant patients (AHA/ACC [Grundy 2019a]; CCS [Pearson 2021]; Parikh 2021).
It is not known if atorvastatin is present in breast milk.
HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Normal concentrations of cholesterol in breast milk are required for infant development (Holmsen 2017; Lecarpentier 2012). Due to the potential for adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer. Available guidelines recommend resuming statin therapy once breastfeeding is completed (AHA/ACC [Grundy 2019a]; CCS [Pearson 2021]).
Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3 to 6 months and the diet should be continued during drug therapy. Atorvastatin serum concentration may be increased when taken with grapefruit juice; avoid concurrent intake of large quantities (>1.2 liters/day).
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2019a]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
Monitor closely for myopathy/rhabdomyolysis. Instruct patients to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).
Onset of action: Initial changes: 3 to 5 days; Maximal reduction in plasma cholesterol and triglycerides: 2 to 4 weeks; LDL reduction: 10 mg/day: 39% (for each doubling of this dose, LDL is lowered approximately 6%)
Absorption: Oral: Rapidly absorbed; extensive first-pass metabolism in GI mucosa and liver
Distribution: Vd: ~381 L
Protein binding: ≥98%
Metabolism: Hepatic via CYP3A4; forms active ortho- and parahydroxylated derivatives and an inactive beta-oxidation product; plasma concentrations are elevated in patients with chronic alcoholic liver disease and Child-Pugh class A and B liver disease
Bioavailability: ~14% (parent drug); ~30% (parent drug and equipotent metabolites)
Half-life elimination: Parent drug: ~14 hours; Equipotent metabolites: 20 to 30 hours
Time to peak, serum: 1 to 2 hours
Excretion: Bile (following hepatic and/or extra-hepatic metabolism; does not appear to undergo enterohepatic recirculation); urine (<2% as unchanged drug)
Hepatic function impairment: Cmax and AUC are each 4-fold greater in patients with Child-Pugh class A disease; Cmax and AUC are ~16-fold and 11-fold increased, respectively, in patients with Child-Pugh class B disease.
Older adult: Plasma concentrations are higher (~40% for Cmax and 30% for AUC).
Sex: Plasma concentrations in women differ from those in men (~20% higher for Cmax and 10% lower for AUC)
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