After a comprehensive review of all available data, the FDA is requesting all statin manufacturers to remove the contraindication in the prescribing information against using statins in pregnant patients. Although statin therapy should be discontinued in most pregnant patients, health care providers should consider the ongoing therapeutic needs of the individual patient, especially patients at very high risk of cardiovascular events during pregnancy, such as patients with homozygous familial hypercholesterolemia or those with established cardiovascular disease. Additionally, breastfeeding is still not recommended in patients taking a statin; health care providers should determine whether it is better to temporarily stop statin therapy while breastfeeding or to continue statin therapy and not have the patient breastfeed. If ongoing statin treatment is necessary, infant formula and other alternatives are available. The FDA expects that removing the contraindication will enable health care providers and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke.
Further information is available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy.
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 (AACE [Jellinger 2017]):
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 (Daniels 2008; NHLBI 2011).
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 (Langslet 2016).
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 (Langslet 2016).
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 (Langslet 2016; McCrindle 2007; NHLBI 2011).
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) (Dipchand 2018; ISHLT [Costanzo 2010]; Kobayashi 2013). Significant drug interactions between statins and immunosuppressant drugs are frequent; many interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (Heeney 2019; Wiggins 2016); 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 (Chin 2002; Chin 2008; ISHLT [Costanzo 2010]).
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 (NHLBI 2011; Stone 2014).
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 (Lins 2003).
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 (Launay-Vacher 2005).
Children ≥10 years and Adolescents: Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
(For additional information see "Atorvastatin: Drug information")
Note: Use in conjunction with lifestyle modification (eg, diet and exercise). When choosing to initiate therapy and selecting dose intensity, consider the following: Age, baseline LDL cholesterol (LDL-C), 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions. High-intensity statin therapy (atorvastatin 40 to 80 mg/day) generally reduces LDL-C by ≥50%. Moderate-intensity statin therapy (atorvastatin 10 to 20 mg/day) 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 (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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 (ACC/AHA [Grundy 2019]; Rosenson 2020; Smilde 2001; Stein 2003).
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.
Homozygous familial hypercholesterolemia:
Note: Multiple lipid-lowering therapies are usually needed to achieve treatment goals; treatment should be guided by an experienced lipid specialist (Rosenson 2020).
High-intensity therapy: Oral: 80 mg once daily (Rosenson 2020).
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 online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, additional lipid-lowering therapy may be warranted (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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 (Pignone 2020).
Moderate-intensity therapy: Oral: 10 to 20 mg once daily to reduce LDL-C by 30% to 49% (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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 (Pignone 2020).
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% (ACC/AHA [Grundy 2019]).
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 (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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% (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
ASCVD risk >20% 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 (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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. Note: Consider familial hypercholesterolemia, which is preferably managed by an experienced lipid specialist (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
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 (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]; AHA/ASA [Kleindorfer 2021]).
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) (AHA [Wiggins 2016]; ISHLT [Costanzo 2010]; KDIGO 2013; Lentine 2021). 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 (AHA [Wiggins 2016]; ISHLT [Costanzo 2010]).
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 (Lentine 2021).
Oral: Initial: 10 mg once daily; increase dose based on response, tolerability, and use of concomitant medications up to 20 mg once daily (AHA [Wiggins 2016]; Lentine 2021).
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 (Stern 1997).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary (Lins 2003).
Peritoneal dialysis: No dosage adjustment necessary (Launay-Vacher 2005).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lipitor: 10 mg, 20 mg, 40 mg, 80 mg
Generic: 10 mg, 20 mg, 40 mg, 80 mg
Yes
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: 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.
Oral: 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.
Store at 20°C to 25°C (68°F to 77°F).
Adjunct to dietary therapy in pediatric patients with heterozygous familial hypercholesterolemia if LDL-C remains ≥190 mg/dL, or if ≥160 mg/dL with family history of premature CHD or presence of ≥2 cardiovascular risk factors (FDA approved in ages 10 to 17 years); adjunct to dietary therapy to decrease elevated serum total and LDL-C, apolipoprotein B (apo-B), and triglyceride levels, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) (FDA approved in adults); adjunct treatment of homozygous familial hypercholesterolemia (FDA approved in adults); treatment of isolated hypertriglyceridemia (Fredrickson type IV); treatment of primary dysbetalipoproteinemia (Fredrickson Type III) (FDA approved in adults).
Primary prevention of cardiovascular disease in high risk patients (FDA approved in adults).
Has also been used in prevention of cardiac allograft vasculopathy.
Atorvastatin may be confused with atomoxetine, lovastatin, nystatin, pitavastatin, pravastatin, rosuvastatin, simvastatin
Lipitor may be confused with labetalol, Levatol, lisinopril, Loniten, Lopid, Mevacor, Zocor, ZyrTEC
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). In patients with severe hepatotoxicity, resolution of symptoms usually occurs within 1 to 4 months; however, some cases of autoimmune hepatitis persist despite statin discontinuation (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: Unknown; inhibition of the CYP450 system, leading to increased plasma concentrations of statins has been postulated, as well as an immune-mediated response (Ref).
Onset: Varied; duration of therapy prior to development of hepatotoxicity ranges from 1 month to several years (Ref). Most cases occur within the first 3 months of initiation or dose escalation (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.
>10%:
Gastrointestinal: Diarrhea (7% to 14%)
Neuromuscular & skeletal: Arthralgia (9% to 12%)
Respiratory: Nasopharyngitis (13%)
1% to 10%:
Cardiovascular: Hemorrhagic stroke (2%)
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%)
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:
Dermatologic: Urticaria
Gastrointestinal: Abdominal distress, cholestasis, eructation, flatulence
Hepatic: Hepatitis, increased serum alkaline phosphatase
Nervous system: Malaise, myasthenia, nightmares
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, joint swelling, muscle fatigue, neck pain
Ophthalmic: Blurred vision
Otic: Tinnitus
Respiratory: Epistaxis
Miscellaneous: Fever
Postmarketing:
Dermatologic: Bullous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Pfeiffer 1998)
Gastrointestinal: Pancreatitis (Lai 2016)
Genitourinary: Cystitis (interstitial) (Huang 2015)
Hematologic & oncologic: Immune thrombocytopenia (Narayanan 2010)
Hepatic: Autoimmune hepatitis (Russo 2014), hepatic failure
Hypersensitivity: Anaphylaxis, angioedema (Hampson 2005)
Immunologic: Immune-mediated necrotizing myopathy (Hasan 2020)
Nervous system: Amnesia (reversible), cognitive dysfunction (reversible) (Tuccori 2014), confusion (reversible), depression, dizziness, fatigue, memory impairment (reversible), peripheral neuropathy
Neuromuscular & skeletal: Dermatomyositis (Spiro 2018), myopathy, myositis, rhabdomyolysis (Dalugama 2018), rupture of tendon (Marie 2008)
Respiratory: Interstitial pulmonary disease
Hypersensitivity to atorvastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy; breastfeeding
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).
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
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Aliskiren: Atorvastatin may increase the serum concentration of Aliskiren. 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
Asunaprevir: 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 in patients taking atazanavir or atazanavir/ritonavir due to the increased risk of myopathy, including rhabdomyolysis. Risk D: Consider therapy modification
Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Atorvastatin. Risk C: Monitor therapy
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
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). 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). Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. Risk D: Consider therapy modification
Daclatasvir: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Danazol: May increase the serum concentration of Atorvastatin. 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
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
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 BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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
Fosphenytoin-Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Consider avoiding coadministration of fosphenytoin/phenytoin and statins. If combined, monitor for decreased therapeutic effects of statins if fosphenytoin/phenytoin is initiated/dose increased. 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
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Atorvastatin. Gemfibrozil may increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates 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
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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
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: HMG-CoA Reductase Inhibitors (Statins) may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Lasmiditan: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Ledipasvir: May enhance the adverse/toxic effect of Atorvastatin. Risk C: Monitor therapy
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
Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of Atorvastatin. Risk X: Avoid combination
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 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
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. Consider temporarily discontinuing atorvastatin during treatment with nirmatrelvir/ritonavir. Risk D: Consider therapy modification
Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates 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
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
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 Atorvastatin. Management: The maximum atorvastatin dose should not exceed 40 mg/day with concurrent use of simeprevir, and use of the lowest necessary atorvastatin dose is recommended. Monitor for atorvastatin toxicity with concomitant use. Risk D: Consider therapy modification
Sofosbuvir: May increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Spironolactone: Atorvastatin may enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Risk C: Monitor therapy
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 BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Talazoparib: Atorvastatin may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Telithromycin: May increase the serum concentration of Atorvastatin. Management: Avoid concomitant use of atorvastatin and telithromycin due to the risk of rhabdomyolysis. If a patient treated with atorvastatin requires telithromycin, discontinue atorvastatin for the duration of telithromycin therapy. Risk D: Consider therapy modification
Teriflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates 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
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).
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).
Atorvastatin is contraindicated in females who may become pregnant.
Adequate contraception is recommended if an HMG-CoA reductase inhibitor is required in females of reproductive potential. Females planning a pregnancy should discontinue the HMG-CoA reductase inhibitor 1 to 2 months prior to attempting to conceive (AHA/ACC [Grundy 2019]).
Atorvastatin is contraindicated in pregnant females.
There are reports of congenital anomalies following maternal use of HMG-CoA reductase inhibitors in pregnancy; however, maternal disease, differences in specific agents used, and the low rates of exposure limit the interpretation of the available data (Godfrey 2012; Lecarpentier 2012). Cholesterol biosynthesis may be important in fetal development; serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid-lowering medications temporarily during pregnancy is not expected to have significant impact on the long-term outcomes of primary hypercholesterolemia treatment.
Atorvastatin should be discontinued immediately if an unplanned pregnancy occurs during treatment.
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Pediatric patients: Baseline: ALT, AST, and CPK; fasting lipid panel (FLP) and repeat ALT and AST should be checked after 4 weeks of therapy; if no myopathy symptoms or laboratory abnormalities, then monitor FLP, ALT, and AST every 3 to 4 months during the first year and then every 6 months thereafter (NHLBI 2011).
Adults:
2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2014):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4 to 12 weeks after initiation or dose adjustment and every 3 to 12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer recommendation: Liver enzyme tests at baseline and repeated when clinically indicated. Measure CPK when myopathy is being considered or may measure CPK periodically in high risk patients (eg, drug-drug interaction). Upon initiation or titration, lipid panel should be analyzed within 2 to 4 weeks.
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.
Geriatric: Plasma concentrations are higher (~40% for Cmax and 30% for AUC).
Gender: Plasma concentrations in women differ from those in men (~ 20% higher for Cmax and 10% lower for AUC)
Tablets (Atorvastatin Calcium Oral)
10 mg (per each): $3.85 - $7.50
20 mg (per each): $5.43 - $10.70
40 mg (per each): $5.49 - $10.70
80 mg (per each): $2.88 - $10.70
Tablets (Lipitor Oral)
10 mg (per each): $13.84
20 mg (per each): $19.74
40 mg (per each): $19.74
80 mg (per each): $20.73
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