Version July 2025
Dosage guidance:
Dosing: Atorvastatin 40 to 80 mg/day is considered a high-intensity statin (generally reduces low-density lipoprotein cholesterol [LDL-C] by ≥50%). Atorvastatin 10 to 20 mg/day is considered a moderate-intensity statin (generally reduces LDL-C by ~30% to 49%). Assess response ~1 to 3 months after initiation of therapy or dose adjustment and every 3 to 12 months thereafter (Ref).
Clinical considerations: Consider combination therapy in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated statin therapy. Refer to individual agents for more information (Ref).
Homozygous familial hypercholesterolemia: Oral: Ezetimibe 10 mg/atorvastatin 40 mg or ezetimibe 10 mg/atorvastatin 80 mg once daily.
Hyperlipidemia: Oral: Dosing range: Ezetimibe 10 mg/atorvastatin 10 to 80 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Ref).
Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced kidney or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of atorvastatin. If muscle symptoms recur, discontinue atorvastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
1% to 10%:
Endocrine & metabolic: Hot flash (2%), hyperkalemia (2%)
Gastrointestinal: Abdominal pain (3%), nausea (3%)
Hepatic: Increased serum alanine aminotransferase (5%), increased serum aspartate aminotransferase (4%)
Nervous system: Dizziness (2%), myasthenia (2%)
Neuromuscular & skeletal: Arthralgia (3%), musculoskeletal pain (4%)
Respiratory: Bronchitis (2%), cough (2%), sinusitis (2%)
Frequency not defined:
Hepatic: Increased liver enzymes
Neuromuscular & skeletal: Myalgia
Hypersensitivity to ezetimibe, atorvastatin, or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy or patients who may become pregnant; breastfeeding.
Concerns related to adverse effects:
• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia.
• 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. 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 kidney failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose-related and is increased with use of strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, elbasvir plus grazoprevir, protease inhibitors), cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day), age ≥65 years, uncontrolled hypothyroidism, and kidney dysfunction; if concurrent use is warranted, consider dose adjustment. Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy associated with HMG-CoA reductase inhibitors use, has also been reported (rarely). Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. 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.
• Kidney impairment: Use with caution in patients with kidney 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).
Special populations:
• Older adults: 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 kidney 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 for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, oral:
Liptruzet 10/10: Ezetimibe 10 mg and atorvastatin 10 mg [DSC]
Liptruzet 10/20: Ezetimibe 10 mg and atorvastatin 20 mg [DSC]
Liptruzet 10/40: Ezetimibe 10 mg and atorvastatin 40 mg [DSC]
Liptruzet 10/80: Ezetimibe 10 mg and atorvastatin 80 mg [DSC]
Tablets (Ezetimibe-Atorvastatin Oral)
10-10 mg (per each): $15.00
10-20 mg (per each): $15.00
10-40 mg (per each): $15.00
10-80 mg (per each): $15.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Administer without regard to meals. Swallow tablets whole; do not crush, dissolve, or chew. Administer ≥2 hours before or ≥4 hours after bile acid sequestrants.
Homozygous familial hypercholesterolemia: As an adjunct to diet for the reduction of elevated total cholesterol, 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.
Hyperlipidemia: As an adjunct to diet for the reduction of elevated total cholesterol, LDL-C, apolipoprotein B (apo B), triglycerides, and non–HDL-C, and to increase HDL-C in patients with primary (heterozygous familial and nonfamilial) hyperlipidemia or mixed hyperlipidemia.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Acipimox: May increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Amiodarone: May increase serum concentration of Atorvastatin. Risk C: Monitor
Antihepaciviral Combination Products: May increase serum concentration of Atorvastatin. Risk X: Avoid
Asciminib: May increase serum concentration of Atorvastatin. Risk X: Avoid
Atazanavir: May increase serum concentration of Atorvastatin. Management: Use of atorvastatin and atazanavir/cobicistat is not recommended. Use the lowest atorvastatin dose necessary and titrate carefully due to the increased risk of statin toxicities. Alternative statins include fluvastatin, pravastatin, and rosuvastatin. Risk D: Consider Therapy Modification
Belumosudil: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of BCRP for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the BCRP substrate may be required. Risk D: Consider Therapy Modification
Belumosudil: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider Therapy Modification
Bile Acid Sequestrants: May decrease absorption of Ezetimibe. Management: Administer ezetimibe at least 2 hours before or 4 hours after any bile acid sequestrant. Risk D: Consider Therapy Modification
Bulevirtide: Ezetimibe may decrease therapeutic effects of Bulevirtide. Risk X: Avoid
Cardiac Glycosides: Atorvastatin may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Ceftobiprole Medocaril: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Clarithromycin: May increase 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 serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Cobicistat: May increase 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 increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase serum concentration of Colchicine. Risk C: Monitor
CycloSPORINE (Systemic): May increase serum concentration of Atorvastatin. Risk X: Avoid
CYP3A4 Inducers (Moderate): May decrease serum concentration of Atorvastatin. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Atorvastatin. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Atorvastatin. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Atorvastatin. Risk C: Monitor
Cyproterone: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Daclatasvir: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Danazol: May increase serum concentration of Atorvastatin. Risk C: Monitor
Danicopan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may increase adverse/toxic effects of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider Therapy Modification
Darolutamide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Darunavir: May increase 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
Elacestrant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Elafibranor: May increase adverse/toxic effects of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk of muscle toxicity may be increased. Risk C: Monitor
Elbasvir and Grazoprevir: May increase 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
Elexacaftor, Tezacaftor, and Ivacaftor: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Eltrombopag: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Eltrombopag: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Encorafenib: May increase serum concentration of Atorvastatin. Encorafenib may decrease serum concentration of Atorvastatin. Risk C: Monitor
Etravirine: May decrease serum concentration of HMG-CoA Reductase Inhibitors (Statins). This applies to atorvastatin, lovastatin and simvastatin. Risk C: Monitor
Fenofibrate and Derivatives: May increase adverse/toxic effects of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Fenofibrate and Derivatives may increase serum concentration of Ezetimibe. Risk C: Monitor
Fibric Acid Derivatives: May increase adverse/toxic effects of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Fibric Acid Derivatives may increase serum concentration of Ezetimibe. Risk X: Avoid
Fosamprenavir: May increase serum concentration of Atorvastatin. Atorvastatin may increase active metabolite exposure of Fosamprenavir. Management: Use the lowest atorvastatin dose necessary and limit the atorvastatin dose to 20 mg daily in patients taking fosamprenavir. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider Therapy Modification
Fostemsavir: May increase 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 increase adverse/toxic effects 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
Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gemfibrozil: May increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid
Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Glecaprevir and Pibrentasvir: May increase serum concentration of Atorvastatin. Risk X: Avoid
Grapefruit Juice: May increase 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 serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary and titrate carefully in patients taking indinavir. Monitor patients carefully for signs and symptoms of myopathy and rhabdomyolysis during coadministration. Risk D: Consider Therapy Modification
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Istradefylline: May increase serum concentration of Atorvastatin. Risk C: Monitor
Itraconazole: May increase serum concentration of Atorvastatin. Management: Limit atorvastatin to a maximum adult dose of 20 mg/day in patients receiving itraconazole. Assess clinical response to ensure that the lowest necessary dose of atorvastatin is used. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Risk D: Consider Therapy Modification
Ketoconazole (Systemic): Atorvastatin may increase adverse/toxic effects of Ketoconazole (Systemic). Specifically, there is a theoretical potential for additive effects on reducing endogenous steroid concentrations. Ketoconazole (Systemic) may increase serum concentration of Atorvastatin. Risk C: Monitor
Lanthanum: May decrease serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider Therapy Modification
Lazertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ledipasvir: May increase adverse/toxic effects of Atorvastatin. Risk C: Monitor
Leflunomide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Leniolisib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Letermovir: May increase 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 serum concentration of Atorvastatin. Atorvastatin may increase 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 serum concentration of Atorvastatin. Risk X: Avoid
Lopinavir: May increase 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 serum concentration of Midazolam. Risk C: Monitor
Nelfinavir: May increase 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 increase adverse/toxic effects of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Nirmatrelvir and Ritonavir: May increase serum concentration of Atorvastatin. Management: Consider temporarily discontinuing atorvastatin during treatment with nirmatrelvir/ritonavir. It is not necessary to hold atorvastatin either prior to or after completion of nirmatrelvir/ritonavir treatment. Risk D: Consider Therapy Modification
Osimertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Oteseconazole: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Posaconazole: May increase serum concentration of Atorvastatin. Risk X: Avoid
Pretomanid: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
QuiNINE: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Raltegravir: May increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Red Yeast Rice: May increase adverse/toxic effects of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid
Regorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase serum concentration of Repaglinide. Risk C: Monitor
Resmetirom: May increase serum concentration of Atorvastatin. Management: Do not exceed atorvastatin doses of 40 mg daily during coadministration with resmetirom. Monitor for increased atorvastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider Therapy Modification
RifAMPin: May increase serum concentration of Atorvastatin. RifAMPin may decrease 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 serum concentration of Atorvastatin. Management: Use lowest atorvastatin dose needed. If ritonavir is combined with another protease inhibitor, see the drug interaction monograph for that protease inhibitor. Risk D: Consider Therapy Modification
Rolapitant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Risk C: Monitor
Roxadustat: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Rupatadine: May increase adverse/toxic effects of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor
Sacubitril: May increase serum concentration of Atorvastatin. Risk C: Monitor
Saquinavir: May increase 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
Selpercatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Simeprevir: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Sofosbuvir: May increase serum concentration of Atorvastatin. Risk C: Monitor
Sparsentan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
St John's Wort: May decrease active metabolite exposure 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 serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Talazoparib: Atorvastatin may increase serum concentration of Talazoparib. Risk C: Monitor
Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Tedizolid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Teriflunomide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ticagrelor: May increase serum concentration of Atorvastatin. Risk C: Monitor
Tipranavir: May increase serum concentration of Atorvastatin. Risk X: Avoid
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may increase myopathic (rhabdomyolysis) effects of Trabectedin. Risk C: Monitor
Trofinetide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider Therapy Modification
Vadadustat: May increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Velpatasvir: May increase serum concentration of Atorvastatin. Risk C: Monitor
Verapamil: Atorvastatin may increase serum concentration of Verapamil. Verapamil may increase 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
Vimseltinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid concomitant use of vimseltinib and BCRP substrates when possible. If combined, monitor for increased effects and toxicities of the BCRP substrate and consider dose adjustments. Risk D: Consider Therapy Modification
Voclosporin: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Voxilaprevir: May increase 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
See individual agents.
Use is contraindicated in patients who may become pregnant.
Use is contraindicated in patients who are pregnant.
Refer to individual monographs for additional information
It is not known if atorvastatin or ezetimibe are present in breast milk.
Use is contraindicated in patients who are breastfeeding.
Refer to individual monographs for additional information.
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 L/day).
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
ACC/AHA blood cholesterol guideline recommendations (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy. When used in combination with fenofibrate, monitor LFTs and signs and symptoms of cholelithiasis.
Monitor closely for myopathy/rhabdomyolysis. Instruct patients to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Ezetimibe: Inhibits absorption of cholesterol at the brush border of the small intestine via the sterol transporter, Niemann-Pick C1-Like1 (NPC1L1). This leads to a decreased delivery of cholesterol to the liver, reduction of hepatic cholesterol stores and an increased clearance of cholesterol from the blood.
Atorvastatin: Inhibits 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).
See individual agents.
