(a TORE va sta tin)
Dyslipidemias:
Dysbetalipoproteinemia: Treatment of primary dysbetalipoproteinemia (Fredrickson type III).
Heterozygous familial and nonfamilial hypercholesterolemia and mixed dyslipidemia: To reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (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 type IIa and IIb).
Heterozygous familial hypercholesterolemia: To reduce total-C, LDL-C, and apo B levels in boys and postmenarche girls 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 two 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.
Hypertriglyceridemia: Treatment of elevated serum triglyceride levels (Fredrickson type IV).
Limitations of use: Has not been studied in conditions where the major lipid abnormality is elevation of chylomicrons (Fredrickson types I and V).
Prevention of cardiovascular disease (CVD):
Primary prevention of cardiovascular disease (high-risk for CVD): To reduce the risk of MI, stroke, and revascularization procedures and angina in adult patients without clinically evident coronary heart disease (CHD) who have multiple CHD risk factors (eg, age, smoking, hypertension, low high-density lipoprotein cholesterol [HDL-C], family history of early CHD); to reduce the risk of MI and stroke in patients with type 2 diabetes and without clinically evident CHD but with multiple risk factors for CHD (eg, retinopathy, albuminuria, smoking, hypertension).
Secondary prevention of cardiovascular disease: To reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for decompensated heart failure, and angina in patients with clinically evident CHD.
Guideline recommendations: Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) to reduce the risk of ASCVD in select adult patients (ACC/AHA [Stone 2013]; NLA [Jacobson 2015]). Refer to respective guideline for specific recommendations.
Hypersensitivity to atorvastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy or women who may become pregnant; breast-feeding
Canadian labeling: Additional contraindications (not in US labeling): Telaprevir Canadian product monograph contraindicates use with atorvastatin.
Primary prevention: Note: Doses should be individualized according to the baseline LDL-cholesterol concentrations and patient response; adjustments should be made at intervals of 2 to 4 weeks
Hypercholesterolemia (heterozygous familial and nonfamilial) and mixed hyperlipidemia (Fredrickson types IIa and IIb): Oral: Initial: 10 or 20 mg once daily; patients requiring >45% reduction in LDL-C may be started at 40 mg once daily; range: 10 to 80 mg once daily
Homozygous familial hypercholesterolemia: Oral: 10 to 80 mg once daily
Prevention of cardiovascular disease/reduce the risk of ASCVD:
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Stone 2013]): Adults ≥21 years:
Primary Prevention:
LDL-C ≥190 mg/dL: High-intensity therapy: 80 mg once daily; if unable to tolerate, may reduce dose to 40 mg once daily
Type 1 or 2 diabetes and age 40 to 75 years: Moderate-intensity therapy: 10 to 20 mg once daily
Type 1 or 2 diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%: High-intensity therapy: 80 mg once daily; if unable to tolerate, may reduce dose to 40 mg once daily
Age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy: 10 to 80 mg once daily
Secondary prevention:
Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik 2015]) and:
Age ≤75 years: High-intensity therapy: 80 mg once daily; if unable to tolerate, may reduce dose to 40 mg once daily
Age >75 years or not a candidate for high intensity therapy: Moderate-intensity therapy: 10 to 20 mg once daily
NLA Dyslipidemia Guideline recommendations (NLA [Jacobson 2015]): Adults ≥20 years:
Primary or secondary prevention: Note: Treatment initiation using either moderate- or high-intensity statin therapy is recommended in qualifying patients based on ASCVD risk assessment criteria and baseline non-HDL-C and LDL-C values. Dosage should be individualized based on patient characteristics, tolerance to therapy, and with consideration for non-HDL-C and LDL-C treatment goals.
Moderate-intensity therapy (30 to 50% reduction of LDL-C generally): 10 to 20 mg once daily
High-intensity therapy ( ≥50% reduction of LDL-C generally): 40 to 80 mg once daily
Intensive lipid-lowering after an ACS event regardless of baseline LDL (off-label use): Oral: Initial: 80 mg once daily; adjust based on patient tolerability (Cannon 2004; Pederson 2005; Schwartz 2001). Note: Currently, the ACC/AHA guidelines for UA/NSTEMI do not specify which statin to use (ACCF/AHA [Anderson 2013]). Also consider the ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013).
Noncardioembolic stroke/TIA (off-label use): Oral: Initial: 80 mg once daily; adjust based on patient tolerability (Adams 2008; Amarenco 2006). Also consider the ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013).
Dosage adjustment for atorvastatin with concomitant medications:
Boceprevir, nelfinavir: Use lowest effective atorvastatin dose (not to exceed 40 mg daily)
Clarithromycin, itraconazole, fosamprenavir, ritonavir (plus darunavir, fosamprenavir, or saquinavir): Use lowest effective atorvastatin dose (not to exceed 20 mg daily)
Lomitapide: Consider atorvastatin dose reduction (per lomitapide manufacturer).
Refer to adult dosing.
Note: Doses should be individualized according to the baseline LDL-cholesterol concentrations and patient response; adjustments should be made at intervals of 4 weeks
Heterozygous familial hypercholesterolemia: Children ≥10 years and Adolescents (females postmenarche): Oral: 10 mg once daily (maximum: 20 mg/day)
Dosage adjustment for atorvastatin with concomitant medications: Refer to adult dosing.
No dosage adjustment necessary.
Dialysis: Due to the high protein binding, atorvastatin is not expected to be cleared by dialysis (not studied)
Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
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.
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 quart/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).
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).
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
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Aliskiren: AtorvaSTATin may increase the serum concentration of Aliskiren. Monitor therapy
Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Consider therapy modification
Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Monitor therapy
Bexarotene (Systemic): May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Boceprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the atorvastatin maximum adult dose to 40 mg daily in patients receiving boceprevir. Monitor clinical response to ensure that the lowest necessary atorvastatin dose is used. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Cimetidine: AtorvaSTATin may enhance the adverse/toxic effect of Cimetidine. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. 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. Consider therapy modification
Clarithromycin: May increase the serum concentration of AtorvaSTATin. Management: Limit atorvastatin to a maximum dose of 20 mg/day (for adults) when used with clarithromycin. If this combination is used, monitor patients more closely for evidence of atorvastatin toxicity. Consider therapy modification
Cobicistat: May increase the serum concentration of AtorvaSTATin. Management: Initiate atorvastatin at the lowest recommended dose and titrate slowly as needed while monitoring closely for evidence of atorvastatin toxicity. Consider therapy modification
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CycloSPORINE (Systemic): May increase the serum concentration of AtorvaSTATin. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. 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. Consider therapy modification
Dabigatran Etexilate: AtorvaSTATin may decrease the serum concentration of Dabigatran Etexilate. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Danazol: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Concurrent use of simvastatin with danazol is contraindicated. Initiate lovastatin at an adult maximum dose of 10 mg/day, and do not exceed 20 mg/day, when danazol is given concomitantly. Fluvastatin, pravastatin and rosuvastatin may pose lower risk. Consider therapy modification
DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Digoxin: AtorvaSTATin may increase the serum concentration of Digoxin. Monitor therapy
DiltiaZEM: AtorvaSTATin may increase the serum concentration of DiltiaZEM. DiltiaZEM may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronedarone: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Efavirenz: May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Elbasvir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification
Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erythromycin (Systemic): May increase the serum concentration of AtorvaSTATin. Monitor therapy
Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fluconazole: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. 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. Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Gemfibrozil may increase the serum concentration of AtorvaSTATin. Avoid combination
Grapefruit Juice: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid concurrent use of GFJ (especially larger amounts) with lovastatin, simvastatin, or atorvastatin. Consider using a lower statin dose or a statin that is less likely to interact when possible. Consider therapy modification
Grazoprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
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. Consider therapy modification
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. 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. Management: Administer ketoconazole with atorvastatin cautiously, and monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities). Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification
Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Midazolam: AtorvaSTATin may increase the serum concentration of Midazolam. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of AtorvaSTATin. Management: Monitor for increased atorvastatin toxicities (eg, myopathy) if these agents are combined. Consider using lower initial doses of atorvastatin. Canadian labeling recommends avoidance of this combination. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
PAZOPanib: AtorvaSTATin may enhance the hepatotoxic effect of PAZOPanib. AtorvaSTATin may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Posaconazole: May increase the serum concentration of AtorvaSTATin. Avoid combination
Protease Inhibitors: May increase the serum concentration of AtorvaSTATin. Management: See full monograph for recommended dose limits. Avoid atorvastatin with tipranavir/ritonavir. Consider therapy modification
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Consider therapy modification
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Ranolazine: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination
Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
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. Consider therapy modification
Spironolactone: AtorvaSTATin may enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy
St Johns Wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider avoiding the concomitant administration of St Johns Wort with interacting HMG-CoA reductase inhibitors in order to avoid the potential for decreased antilipemic effects. Monitor for decreased effects during concomitant therapy. Consider therapy modification
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Telaprevir: May increase the serum concentration of AtorvaSTATin. Avoid combination
Telithromycin: May increase the serum concentration of AtorvaSTATin. Management: Consider limiting atorvastatin to a max (adult) dose of 20 mg/day when used with telithromycin. Although not a specific recommendation in atorvastatin labeling, this is consistent with dosing for other strong CYP3A4 inhibitors, including clarithromycin. Consider therapy modification
Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy
Ticagrelor: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Tipranavir: May increase the serum concentration of AtorvaSTATin. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy
Velpatasvir: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Verapamil: AtorvaSTATin may increase the serum concentration of Verapamil. Verapamil may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with verapamil. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Voriconazole: May increase the serum concentration of AtorvaSTATin. Management: Monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities) during concomitant treatment, and reduce atorvastatin dose when possible. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification
2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 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 's labeling: 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 2-4 weeks.
>10%:
Gastrointestinal: Diarrhea (7% to 14%)
Neuromuscular & skeletal: Arthralgia (9% to 12%)
Respiratory: Nasopharyngitis (13%)
2% to 10%:
Cardiovascular: Hemorrhagic stroke (2%)
Central nervous system: Insomnia (5%)
Endocrine & metabolic: Diabetes mellitus (6%)
Gastrointestinal: Nausea (7%), dyspepsia (6%)
Genitourinary: Urinary tract infection (7% to 8%), cystitis (interstitial; Huang 2015)
Hepatic: Increased serum transaminases ( ≤2%)
Neuromuscular & skeletal: Limb pain (9%), myalgia (4% to 8%), musculoskeletal pain (5%), muscle spasm (4% to 5%)
Respiratory: Pharyngolaryngeal pain (3% to 4%)
<2% (Limited to important or life-threatening): Abdominal pain, abnormal hepatic function tests, alopecia, anaphylaxis, anemia, angioedema, anorexia, cholestasis, cholestatic jaundice, cognitive dysfunction (reversible), confusion (reversible), depression, elevated glycosylated hemoglobin (HbA1c), epistaxis, eructation, erythema multiforme, gynecomastia, hematuria, hepatic failure, hepatitis, hyperglycemia, hypoesthesia, increased creatinine phosphokinase, increased serum alkaline phosphatase, increased serum glucose, jaundice, joint swelling, muscle fatigue, myasthenia, myopathy, myositis, neck stiffness, nightmares, pancreatitis, paresthesia, peripheral edema, peripheral neuropathy, rhabdomyolysis, rupture of tendon, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
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.
Plasma concentrations are higher (~40% for Cmax and 30% for AUC).
Plasma concentrations in women differ from those in men (~ 20% higher for Cmax and 10% lower for AUC)
Concerns related to adverse effects:
- Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported.
- Hepatotoxicity: Persistent elevations in serum transaminases have been reported; upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels. Postmarketing reports of fatal and nonfatal hepatic failure have been reported and are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. If an alternate etiology is not identified, do not restart atorvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated and if signs/symptoms of liver injury occur. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.
- Myopathy/rhabdomyolysis: Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, protease inhibitors), cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day); if concurrent use is warranted, consider lower starting and maintenance doses of atorvastatin. Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Uncomplicated myalgia immune-mediated necrotizing myopathy (IMNM) associated with HMG-CoA reductase inhibitors use has also been reported. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed/suspected.
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.
- Renal impairment: Use with caution in patients with renal impairment; these patients are predisposed to myopathy.
- 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 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).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Use with caution in patients with advanced age, these patients are predisposed to myopathy.
- Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, trauma, uncontrolled seizures, severe metabolic, endocrine, or electrolyte disorders). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period (ACC/AHA [Fleisher 2014). Postoperative 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).
Other warnings/precautions:
- Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Atorvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).
- Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
X
Studies in animals and pregnant women have shown evidence of fetal abnormalities and use is contraindicated in women who are or may become pregnant. 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.
HMG-CoA reductase inhibitors should be discontinued prior to pregnancy (ADA 2013). If treatment of dyslipidemias is needed in pregnant women or in women of reproductive age, other agents are preferred (Berglund 2012; Stone 2013). The manufacturer recommends administration to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.
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).
Oral: Rapidly absorbed; extensive first-pass metabolism in GI mucosa and liver
Vd: ~381 L
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 Childs-Pugh class A and B liver disease
Bile (following hepatic and/or extra-hepatic metabolism; does not appear to undergo enterohepatic recirculation); urine (<2% as unchanged drug)
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%)
Serum: 1 to 2 hours
Parent drug: ~14 hours; Equipotent metabolites: 20 to 30 hours
≥98%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, joint pain, nausea, insomnia, rhinitis, or pharyngitis. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), urinary retention, change in amount of urine passed, pain with urination, dysphagia, severe loss of strength and energy, severe muscle pain, severe muscle tenderness, or severe muscle weakness (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.