Version July 2025
Premature discontinuation of any oral anticoagulant, including apixaban, increases the risk of thrombotic events. If anticoagulation with apixaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
Epidural or spinal hematomas may occur in patients treated with apixaban who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants; a history of traumatic or repeated epidural or spinal punctures; a history of spinal deformity or spinal surgery; optimal timing between the administration of apixaban and neuraxial procedures is not known.
Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.
The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP and Kelly Rudd, PharmD, BCPS, CACP, FCCP.
Atrial fibrillation/flutter (atrial flutter is an off-label use):
Note: Used to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation or atrial flutter and no history of moderate to severe mitral stenosis or mechanical valve replacement (Ref).
Oral: 5 mg twice daily unless patient has any 2 of the following: Age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromole/L), then reduce dose to 2.5 mg twice daily.
Post-percutaneous coronary intervention with stent placement and atrial fibrillation/flutter: Oral: 5 mg twice daily unless patient has any 2 of the following: Age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromole/L), then reduce dose to 2.5 mg twice daily; administer with an appropriate antithrombotic regimen including clopidogrel (preferred P2Y12 inhibitor in this situation) with or without aspirin, depending on risks for thrombosis and bleeding, and time since percutaneous coronary intervention (PCI) (Ref). It is recommended to discontinue aspirin 1 to 4 weeks after PCI and continue apixaban and clopidogrel (Ref).
Heparin-induced thrombocytopenia (off-label use): Note: For treatment of acute heparin-induced thrombocytopenia, either as initial therapy in selected hemodynamically stable patients or after initial therapy with a parenteral non-heparin anticoagulant (Ref). Some experts recommend avoiding use of direct oral anticoagulants as initial therapy in the setting of life-threatening or limb-threatening thrombosis or in other clinically unstable patients (Ref).
Heparin-induced thrombocytopenia with or without thrombosis: Oral: 10 mg twice daily for 7 days or until platelet count recovery, whichever is longer, followed by 5 mg twice daily. Note: If initially treated with a parenteral non-heparin anticoagulant, can transition to 5 mg twice daily after platelet count recovery. However, if the parenteral non-heparin anticoagulant is administered for <7 days, transition to 10 mg twice daily; then after a total of 7 days with non-heparin anticoagulation, reduce to 5 mg twice daily (Ref). For patients without thrombosis, may consider starting 5 mg twice daily regardless of whether parenteral anticoagulation was used initially (Ref).
Duration: Not well established:
Heparin-induced thrombocytopenia without thrombosis: Typically, 4 weeks to 3 months (Ref). Alternatively, may discontinue anticoagulation after platelet count recovery, potentially resulting in a shorter duration (Ref).
Heparin-induced thrombocytopenia with thrombosis: Typically, 3 to 6 months (Ref).
Left ventricular thrombus, treatment or prophylaxis (off-label use):
Treatment:
Post myocardial infarction:
Note: When an antiplatelet agent is used in combination with an anticoagulant, selection and duration of antiplatelet therapy for myocardial infarction (MI) may vary; consider risks of bleeding and thrombotic events when choosing antithrombotic therapy combinations (Ref).
Oral: 5 mg twice daily for ~3 months in patients with acute MI or ≥3 to 6 months in patients with distant MI (Ref). Duration may vary based on follow-up imaging (eg, assessment of thrombus resolution and left ventricular [LV] function) and shared decision making; indefinite therapy may be considered if LV function does not improve (eg, reduced systolic function, persistent apical akinesis or dyskinesis) or in patients with other ongoing thrombotic risk factors (Ref).
Nonischemic dilated cardiomyopathy: Oral: 5 mg twice daily for ≥3 to 6 months; duration may vary based on follow-up imaging (eg, assessment of thrombus resolution and LV function) and shared decision making; indefinite therapy may be considered even after thrombus resolution if LV function does not improve (eg, reduced systolic function, persistent apical akinesis or dyskinesis) or in patients with other ongoing thrombotic risk factors (Ref).
Prophylaxis for high-risk patients post myocardial infarction:
Note: May be used for high-risk patients (eg, ejection fraction <40% and/or anteroapical wall motion abnormality) to prevent LV thrombus. When an antiplatelet agent is used in combination with an anticoagulant, selection and duration of antiplatelet therapy for MI may vary; consider risks of bleeding and thrombotic events when choosing antithrombotic therapy combinations (Ref).
Oral: 5 mg twice daily for 1 to 3 months; duration may vary based on follow-up imaging (eg, assessment of LV function) and shared decision making (Ref).
Venous thromboembolism, treatment:
Oral: 10 mg twice daily for 7 days followed by 5 mg twice daily.
Duration of therapeutic anticoagulation (first episode, general recommendations):
Provoked venous thromboembolism with a transient risk factor: 3 months with reassessment for resolution of the provoking factor (Ref).
Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of venous thromboembolism (VTE) recurrence and bleeding (Ref).
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals (Ref).
Indefinite anticoagulation (reduced-intensity dosing for prophylaxis against venous thromboembolism recurrence): Note: For patients at elevated risk of recurrent VTE following at least 6 months of therapeutic anticoagulation. This reduced-intensity regimen is not recommended if indefinite full anticoagulation is indicated (Ref): Oral: 2.5 mg twice daily (Ref).
Venous thromboembolism, prophylaxis:
Total hip arthroplasty or total knee arthroplasty: Oral: 2.5 mg twice daily beginning 12 to 24 hours postoperatively.
Duration: Optimal duration of prophylaxis is unknown but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (Ref); some experts suggest a duration in the lower end of the range (10 to 14 days) for total knee arthroplasty or higher end of range (~30 days) for THA (Ref).
Patients with multiple myeloma receiving immunomodulatory therapy who are at a higher risk for venous thromboembolism (off label): Oral: 2.5 mg twice daily during immunomodulatory therapy; duration of VTE prophylaxis may also depend on risk factors (Ref).
Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol for additional detail.
Transitioning from another anticoagulant to apixaban:
Transitioning from low-molecular-weight heparin or fondaparinux (therapeutic dose) to apixaban: Discontinue the parenteral anticoagulant and initiate apixaban within 2 hours prior to when the next scheduled dose of the parenteral anticoagulant was scheduled to be administered (Ref).
Transitioning from unfractionated heparin continuous infusion to apixaban: Start apixaban when the unfractionated heparin infusion is stopped (consult local protocol if the aPTT is above the target range) (Ref).
Transitioning from warfarin to apixaban: Discontinue warfarin and initiate apixaban when the INR is <2 (Ref).
Transitioning from apixaban to another anticoagulant:
Transitioning from apixaban to a parenteral anticoagulant: Start the parenteral anticoagulant when the next dose of apixaban was scheduled to be administered (Ref).
Transitioning from apixaban to warfarin:
Note: Apixaban can elevate the INR, complicating interpretation if overlapped with warfarin. To minimize interference, check INR near the end of apixaban dosing interval (Ref).
Some experts suggest overlapping apixaban with warfarin until INR is within the therapeutic range (Ref). An alternative is to stop apixaban, then start warfarin the same day, and bridge with a parenteral anticoagulant until INR is within the therapeutic range (Ref).
Transitioning between direct oral anticoagulants: Start the new direct oral anticoagulant (DOAC) when the next dose of the previous DOAC was scheduled to be administered (Ref).
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.
Note: Clinical trials have excluded patients with severe kidney impairment (eg, patients with CrCl <25 mL/minute (Ref)). Retrospective studies suggest similar efficacy and no increased bleeding risk with apixaban compared to warfarin in these patients (Ref) or in those requiring dialysis (Ref). However, some experts avoid use of apixaban until more robust data become available (Ref).
Atrial fibrillation and atrial flutter (off-label)
Altered kidney function: Oral:
SCr <1.5 mg/dL (133 micromole/L): No dosage adjustment necessary unless ≥80 years of age and body weight ≤60 kg, then reduce dose to 2.5 mg twice daily.
SCr ≥1.5 mg/dL (133 micromole/L) and either ≥80 years of age or body weight ≤60 kg: 2.5 mg twice daily.
CrCl <25 mL/minute or end-stage kidney disease not requiring dialysis: Use with caution due to limited available data. There is uncertainty about the best dose in this patient population, especially in patients with CrCl <15 mL/minute (Ref). Manufacturer’s labeling recommends the same doses as recommended for patients with SCr ≥1.5 mg/dL. Alternatively, some experts suggest apixaban 2.5 mg twice daily for CrCl <25 mL/minute (Ref).
Hemodialysis, intermittent (thrice weekly): Note: Use with caution. Two small randomized controlled trials of apixaban versus warfarin in patients on dialysis showed a higher incidence of clinically significant bleeding with use of either agent compared to stroke events (Ref). Some experts avoid anticoagulation in this population except in certain cases where there are likely to be substantial benefits without excess bleeding risk (Ref). When apixaban is used, there is uncertainty about the best dose. A study conducted in patients with end-stage kidney disease receiving 5 mg twice daily showed that median steady state AUC0-12 is 1.8 times that of patients with normal kidney function (2,475 versus 1,374 ng*hour/mL, respectively), although the AUCs were similar to those reported in patients with CrCl 15 to 60 mL/minute receiving the same dose (Ref). Retrospective clinical data are conflicting, with one study finding labeled dosing to be optimal in terms of thromboembolic event reduction and mortality (Ref), while another suggests similar efficacy but higher bleeding with 5 mg twice daily doses (Ref).
Minimally dialyzable (AUC decreased by 14% over 4 hours) (Ref):
Oral: According to the manufacturer, no dosage adjustment necessary unless ≥80 years of age or body weight ≤60 kg, then reduce to 2.5 mg twice daily. Some experts prefer 2.5 mg twice daily for any patient receiving hemodialysis (Ref).
Left ventricular thrombus, treatment or prophylaxis (off-label use):
Altered kidney function: Oral:
Note: Specific data in patients with kidney impairment are lacking; several small studies utilized dose adjustment that is consistent with atrial fibrillation as follows (Ref):
SCr <1.5 mg/dL (133 micromole/L): No dosage adjustment necessary unless ≥80 years of age and body weight ≤60 kg, then reduce dose to 2.5 mg twice daily.
SCr ≥1.5 mg/dL (133 micromole/L) and either ≥80 years of age or body weight ≤60 kg: 2.5 mg twice daily.
Venous thromboembolism, treatment or prophylaxis:
Altered kidney function: Oral: According to the manufacturer, no dosage adjustment necessary for any degree of kidney impairment.
Hemodialysis, intermittent (thrice weekly): Minimally dialyzable (AUC decreased by 14% over 4 hours) (Ref).
Oral: According to the manufacturer, no dosage adjustment necessary. Note: Use with caution due to limited available data (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Clinical trials used to support the FDA-approved indications excluded patients with more severe liver impairment, and therefore, the manufacturer’s labeling recommends against use in patients with severe (Child-Turcotte-Pugh class C) liver impairment and indicates no dose recommendation can be provided for moderate impairment (Child-Turcotte-Pugh class B). Evidence to support use in liver insufficiency comes from postmarketing, primarily single-center, observational studies. In a single-dose study, there were no differences in the apixaban pharmacokinetic or pharmacodynamic profile in Child-Turcotte-Pugh class A and B patients compared to healthy controls (Ref). No pharmacokinetic or pharmacodynamic data are available in severe liver impairment (Child-Turcotte-Pugh class C).
If treatment is initiated, a direct oral anticoagulant (DOAC) such as apixaban, may be considered over a vitamin K antagonist (VKA) in patients with liver dysfunction if there is concern that PT/INR will be an inaccurate measure of VKA anticoagulation.
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Dosage adjustment in patients with liver impairment prior to treatment initiation |
Dosage adjustment in patients with chronic disease progression or acute worsening of liver function during treatment (eg, progression from Child-Turcotte-Pugh class A to B) | |||
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Child-Turcotte-Pugh class A or B at baseline |
Child-Turcotte-Pugh class C at baseline |
Progression from baseline to Child-Turcotte-Pugh class A or B |
Progression from baseline to Child-Turcotte-Pugh class C | |
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a In general, use not recommended in patients with liver impairment that also have platelet count <50,000/mm3, high-risk esophageal varices (ie, stigmata of recent bleeding), or severe kidney impairment (ACG [Simonetto 2020]; Biolato 2022; Vandenberk 2023). | ||||
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b Majority of data are based on studies in patients with portal vein thrombosis. | ||||
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Atrial fibrillation/flutter | ||||
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Atrial fibrillation/flutter (atrial flutter is an off-label use) |
No dosage adjustment necessary (Coons 2022; Diesveld 2024; Frost 2021; expert opinion). |
Avoid use (manufacturer's labeling). |
No dosage adjustment necessary (Coons 2022; Frost 2021). Increased bleeding events have been observed in more advanced liver impairment (Child-Turcotte-Pugh B or C) (Oldham 2022; Semmler 2021). |
Use of an alternative agent may be preferred (Semmler 2021; expert opinion). However, if use of apixaban is deemed appropriate, no dosage adjustment necessary; use with caution (expert opinion). |
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Heparin-induced thrombocytopenia | ||||
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Heparin-induced thrombocytopenia (off-label use) |
Data to support use is lacking (Frost 2021; expert opinion). |
Use not recommended (expert opinion) |
No dosage adjustment necessary (Frost 2021; expert opinion). Bleeding events have been more frequently observed in patients with advanced liver impairment (Child-Turcotte-Pugh B or C) (Semmler 2021). |
Use of an alternative agent may be preferred (Semmler 2021; expert opinion). However, if use of apixaban is deemed appropriate, no dosage adjustment necessary; use with caution (expert opinion). |
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Left ventricular thrombus, treatment or prophylaxis | ||||
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Left ventricular thrombus, treatment or prophylaxis (off-label use) |
Data to support use is lacking (expert opinion). |
Avoid use (Ghani 2020; expert opinion). |
Data to support use is lacking (expert opinion). |
Avoid use (Ghani 2020; expert opinion). |
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Venous thromboembolism | ||||
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Venous thromboembolism treatment (for initiation or maintenance of treatment)b |
No dosage adjustment necessary (Diesveld 2024; EASL 2022; Elhosseiny 2019; Frost 2021; Intagliata 2016; Northup 2021; Semmler 2021) |
Avoid use (EASL 2022; Martens 2022; manufacturer labeling). |
No dosage adjustment necessary (Coons 2022; Elhosseiny 2019; ESAL 2022; Frost 2021). Increased bleeding events have been observed in more advanced liver impairment (Child-Turcotte-Pugh B or C) (Oldham 2022; Semmler 2021). |
Strongly consider discontinuation and use alternative agent (ESAL 2022; Oldham 2022; Semmler 2021; expert opinion). |
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Indefinite anticoagulation (reduced-intensity dosing for prophylaxis against venous thromboembolism recurrence) |
No dosage adjustment necessary (Diesveld 2024; EASL 2022; Northup 2021) |
No dosage adjustment likely necessary since this is a lower-dose regimen; use with caution (expert opinion); some guidelines suggest use should be avoided (EASL 2022) |
No dosage adjustment necessary (EASL 2022). |
Given this is a lower-dose regimen, no dosage adjustment necessary (expert opinion); some guidelines suggest use should be avoided (EASL 2022) |
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Venous thromboembolism prophylaxis |
No dosage adjustment necessary (Diesveld 2024; EASL 2022; expert opinion). |
Given this is a lower-dose regimen, may use with caution (no dosage adjustment necessary) (expert opinion); some guidelines suggest use should be avoided (ACG [Simonetto 2020]; EASL 2022). |
No dosage adjustment necessary (EASL 2022; expert opinion). |
Given this is a lower-dose regimen, may continue with caution (no dosage adjustment necessary) (expert opinion); some guidelines suggest use should be avoided (ACG [Simonetto 2020]; EASL 2022). |
The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥3 0 kg/m2): No dosage adjustment necessary (Ref). Refer to adult dosing for indication-specific doses.
Rationale for recommendations:
Pharmacokinetic studies have demonstrated variability in apixaban drug concentrations or anti-factor Xa activity with some studies reporting a modest reduction in exposure with obesity (Ref). However, retrospective studies have not reported adverse clinical outcomes despite possible pharmacokinetic alterations (Ref). Several meta-analyses of patients with atrial fibrillation and a BMI ≥30 kg/m2 have reported a lower incidence of stroke and major bleeding events with the use of standard dose direct oral anticoagulants when compared to warfarin (Ref). In patients with venous thromboembolism, retrospective data suggest that no dosage adjustment is necessary in patients with a BMI ≥40 kg/m2 or who weigh >100 to 300 kg. A meta-analysis of this population reported similar rates of recurrent thrombotic events and decreased odds of major bleeding with standard dose direct oral anticoagulants when compared to warfarin (Ref).
The International Society on Thrombosis and Haemostasis suggests not to regularly monitor peak and trough drug-specific concentrations due to insufficient data to impact clinical decisions (Ref). Others have suggested drug-specific concentrations could be considered in select populations (eg, very high BMI), recognizing the poor correlation to clinical efficacy and safety (Ref).
Refer to adult dosing.
Atrial fibrillation/flutter (atrial flutter is an off-label use): Note: Used to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation or atrial flutter and no history of moderate to severe mitral stenosis or mechanical valve replacement (Ref). If patient is ≥80 years of age and either weighs ≤60 kg or has a serum creatinine ≥1.5 mg/dL (133 micromole/L), then reduce dose to 2.5 mg twice daily.
Left ventricular thrombus, treatment or prophylaxis (off-label use): Note: Specific data are lacking; several small studies utilized dose adjustment that is consistent with atrial fibrillation as follows: If patient is ≥80 years of age and either weighs ≤60 kg or has a serum creatinine ≥1.5 mg/dL (133 micromole/L), then reduce dose to 2.5 mg twice daily (Ref).
Apixaban may increase the risk of bleeding (hemorrhage), including severe and potentially fatal major bleeding as defined by the International Society on Thrombosis and Hemostasis (Ref).
Onset: Variable; for anticoagulants in general, risk may be highest within 3 months of initiation (Ref).
Risk factors:
General (any anticoagulant):
• History of GI bleeding (Ref)
• History of prior bleeding event (Ref)
• Hemostatic abnormalities (Ref)
• Kidney or hepatic impairment (Ref)
• Coadministration of drugs that affect hemostasis or interact to increase exposure (Ref)
• Alcohol use (Ref)
• Older patients (Ref)
• Nonwhite race (Ref)
• History of stroke (Ref)
• Hypertension (Ref)
• Diabetes (Ref)
• Malignancy (Ref)
• Excessive fall risk (Ref)
Spinal hematoma or epidural intracranial hemorrhage may occur in patients treated with apixaban who are receiving neuraxial anesthesia or undergoing spinal puncture; may result in long-term or permanent paralysis. Spontaneous spinal or epidural hematomas (SEH) have also been reported (Ref).
Mechanism: SEH due to neuraxial anesthesia or spinal puncture is related to trauma in the presence of impaired hemostasis with apixaban. Spontaneous SEH may be due to sudden increases in thoracic and/or abdominal pressure (Ref).
Onset: Spontaneous SEH: Variable; case reports have occurred from 10 days to 3 years after apixaban initiation (Ref).
Risk factors:
• Use of indwelling epidural catheters
• Concomitant administration of other drugs that affect hemostasis (eg, aspirin, nonsteroidal anti-inflammatory drugs, platelet inhibitors, other anticoagulants)
• History of traumatic or repeated epidural or spinal punctures
• History of spinal deformity or surgery
• If optimal timing between administration of apixaban and neuraxial procedures is unknown
• Older patients (Ref)
• Females (Ref)
• Hemostatic abnormalities (Ref)
• Epidural rather than spinal anesthesia (Ref)
• Challenging neuraxial procedures (Ref)
• Risk factors for spontaneous SEH: Stretch exercises, Valsalva maneuvers, defecation, hypertension, structural extradural anomalies, and rupture of fragile epidural veins by an adjacent herniated disk (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Hematologic & oncologic: Hemorrhage (≤15%; major hemorrhage: ≤2%; clinically relevant nonmajor hemorrhage: 4%)
1% to 10%:
Endocrine & metabolic: Heavy menstrual bleeding (1%)
Gastrointestinal: Gingival hemorrhage (≤1%), nausea (3%)
Genitourinary: Hematuria (≤2%)
Hematologic & oncologic: Anemia (3%), bruise (1% to 2%), hematoma (1% to 2%), rectal hemorrhage (≤1%)
Respiratory: Epistaxis (≤4%), hemoptysis (≤1%)
<1%:
Cardiovascular: Perioperative blood loss, syncope
Dermatologic: Dermal hemorrhage, skin rash, wound secretion
Endocrine & metabolic: Increased gamma-glutamyl transferase
Gastrointestinal: Gastrointestinal hemorrhage, hematemesis, hematochezia, hemorrhoidal bleeding, melena
Genitourinary: Abnormal uterine bleeding, genital bleeding
Hematologic & oncologic: Hemophthalmos, periorbital hematoma, petechia, postoperative hematoma (incision site), postprocedural hemorrhage, puncture site bleeding, thrombocytopenia, wound hemorrhage
Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases
Hypersensitivity: Allergic angioedema, anaphylaxis
Local: Hematoma at injection site, incision site hemorrhage
Nervous system: Intracranial hemorrhage
Neuromuscular & skeletal: Muscle hemorrhage
Ophthalmic: Conjunctival hemorrhage, retinal hemorrhage
Postmarketing:
Cardiovascular: Thrombosis (with premature discontinuation) (Ref)
Hematologic & oncologic: Spinal hematoma (rare: <1%) (Ref)
Nervous system: Epidural intracranial hemorrhage (rare: <1%) (Ref)
Ophthalmic: Periorbital edema (Ref)
US labeling: Severe hypersensitivity reaction (ie, anaphylaxis) to apixaban or any component of the formulation; active pathological bleeding
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to apixaban or any component of the formulation; lesions or conditions at increased risk of clinically significant bleeding (eg, cerebral infarct [ischemic or hemorrhagic], active peptic ulcer disease with recent bleeding; patients with spontaneous or acquired impairment of hemostasis); hepatic disease associated with coagulopathy and clinically relevant bleeding risk; concomitant systemic treatment with agents that are strong inhibitors of both CYP3A4 and P-glycoprotein (P-gp); concomitant treatment with any other anticoagulant including unfractionated heparin (except at doses used to maintain patency of central venous or arterial catheter), low molecular weight heparins, heparin derivatives (eg, fondaparinux), and oral anticoagulants including warfarin, dabigatran, rivaroxaban except when transitioning to or from apixaban therapy
Disease-related concerns:
• Antiphospholipid syndrome: Use not recommended for patients with triple-positive antiphospholipid syndrome (APS). Patients with APS (especially if triple positive for all 3 antiphospholipid antibodies [lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I]) may have increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.
• Atrial fibrillation: When used to prevent stroke in patients with atrial fibrillation, an increased risk of stroke was observed upon transition from apixaban to warfarin in clinical trials. In patients with atrial fibrillation who had an acute ischemic stroke while receiving a direct oral anticoagulant (DOAC) (eg, apixaban), guidelines generally support withholding oral anticoagulation until 1 to 2 weeks after the ischemic stroke (time frame may vary with shorter times for transient ischemic attack or small, nondisabling stroke and longer times for moderate to severe stroke) (AHA/ASA [Kernan 2014]).
• GI/bariatric surgery: Altered absorption: Evaluate the risk versus benefit of possible decreased drug absorption. Impact may be greater for malabsorptive procedures that alter normal intestinal anatomy versus restrictive gastric procedures. Primary site of absorption and interaction with CYP3A4 or P-glycoprotein (P-gp) must be considered. Expression of CYP3A4 is found throughout the entire small intestine but is most prevalent in the duodenum and proximal jejunum. Expression of P-gp is highest in the distal small bowel and colon (Hakeam 2017). More than half of an apixaban dose is absorbed in the distal small bowel or ascending colon. Therefore, distal small bowel and colectomy surgeries could possibly reduce the bioavailability of apixaban. Procedures that preserve the majority of the jejunum (traditional Roux-en-Y gastric bypass) are unlikely to significantly affect apixaban bioavailability (Hakeam 2017). Peak apixaban concentrations and total AUC are reduced by 60% when released in the distal small intestine and further reduced to 90% and 84%, respectively, when released in the ascending colon (Frost 2013). The available data are conflicting for absorption alterations, derived from small populations, and underrepresent individual direct oral anticoagulants and distinct surgeries (Kröll 2017; Kröll 2018; Lee 2013; Rottenstreich 2018).
• Kidney impairment: Systemic exposure increases with worsening kidney function. Clinical trials for venous thromboembolism (treatment or prophylaxis) and atrial fibrillation (to prevent stroke and systemic embolism) excluded patients either with serum creatinine >2.5 mg/dL or CrCl <25 mL/minute (Agnelli 2013a; Agnelli 2013b; Connolly 2011; Granger 2011) or with CrCl <30 mL/minute (ADVANCE-1 [Lassen 2009]; ADVANCE-2 [Lassen 2010b]; ADVANCE-3 [Lassen 2010a]). Therefore, there are no clinical trial data on safety or efficacy in patients with advanced chronic kidney disease (CKD). Use with caution in patients with kidney impairment, worsening kidney function, and with interventions such as hemodialysis; dosage adjustment may be required.
• Valvular disease: Avoid use in patients with surgically implanted mechanical heart valve, transcatheter aortic valve replacement with no other indication for anticoagulation, moderate to severe mitral stenosis, or significant rheumatic heart disease. However, may be used in patients with atrial fibrillation and native aortic valve disease, tricuspid valve disease, mitral regurgitation, or surgical bioprosthetic mitral valve replacement when anticoagulation is required (ACC/AHA [Joglar 2024]; ACC/AHA [Otto 2021]; Gaasch 2020).
Other warnings/precautions:
• Elective surgery/procedure: When temporary interruption is necessary before surgery or a procedure, the timing of discontinuation depends on kidney function and risk for bleeding complications. In patients with CrCl ≥30 mL/minute, discontinue therapy approximately 24 to 48 hours before surgery, depending on risk for bleeding. In patients with CrCl <30 mL/minute, may consider discontinuing therapy ~48 to 72 hours before surgery, depending on risk for bleeding. Consider discontinuing for a longer period of time in patients undergoing major surgery, spinal puncture, or insertion of a spinal or epidural catheter or port. After discontinuation, bridging with low molecular weight heparin or heparin perioperatively is not necessary and may increase risk of bleeding. When there is adequate hemostasis after surgery, may reinstitute therapy after ≥24 hours depending on risk for bleeding. Specific considerations can be found in expert scientific statements and consensus pathways (ACC [Doherty 2017]; ACC/AHA [Joglar 2024]; ACCP [Douketis 2022b]; AHA [Raval 2017]).
• Body weight: Systemic exposure may be increased by 20% to 30% in patients <50 kg and decreased by 20% to 30% in patients >120 kg; dosage reduction is recommended for patients with atrial fibrillation weighing ≤60 kg and either ≥80 years of age or with a serum creatinine ≥1.5 mg/dL (133 micromole/L).
• Spinal or epidural hematoma: Neuraxial intervention is best performed when the anticoagulant effect of apixaban is low. Guidelines recommend discontinuation of apixaban 72 hours prior to neuraxial intervention; if <72 hours, consider checking anti-factor Xa level (Horlocker 2018). For unanticipated neuraxial intervention, guidelines recommend waiting at least 26 to 30 hours following the last apixaban dose when using prophylactic dosing (eg, 2.5 mg twice daily) before neuraxial puncture and/or catheter manipulation/withdrawal (Gogarten 2010; Horlocker 2018). When higher doses are used (eg, 5 mg twice daily) or in patients with SCr ≥1.5 mg/dL, age ≥80 years, or body weight ≤60 kg, waiting 40 to 75 hours following the last apixaban dose is recommended (Gogarten 2010; Horlocker 2018). Avoid apixaban administration for at least 6 hours following neuraxial puncture or neuraxial catheter withdrawal (Horlocker 2018); if traumatic puncture occurs, avoid apixaban administration for at least 48 hours.
Eliquis 0.5 mg tablet for oral suspension and 0.15 mg sprinkle capsule: FDA approved April 2025; anticipated availability currently unknown. Eliquis tablets for oral suspension and sprinkle capsules are intended for the treatment of venous thromboembolism (VTE) and reduction in the risk of recurrent VTE in pediatric patients from birth and older after at least 5 days of initial anticoagulant treatment. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Eliquis: 2.5 mg, 5 mg
Tablet Therapy Pack, Oral:
Eliquis DVT/PE Starter Pack: 5 mg (74 ea)
No
Tablet Therapy Pack (Eliquis DVT/PE Starter Pack Oral)
5 mg (per each): $12.13
Tablets (Eliquis Oral)
2.5 mg (per each): $12.13
5 mg (per each): $12.13
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Eliquis: 2.5 mg, 5 mg
Generic: 2.5 mg, 5 mg
Oral: Administer without regard to meals. After hip/knee replacement, initial dose should be administered 12 to 24 hours postoperatively. If patient unable to swallow whole tablets, may crush 5 mg or 2.5 mg tablets and suspend in 60 mL of water, D5W, or apple juice or mix with applesauce; administer immediately. Crushed tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours. Note: Also available in capsules and tablets for oral suspension for pediatric use only; tablets are to be used for adult dosing.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral tablets:
Note: Absorption may be theoretically reduced if administered post-pylorically; consider therapeutic drug monitoring (Ref). Some experts recommend using an alternative anticoagulant over post-pyloric apixaban administration (Ref).
Gastric (eg, NG, G-tube ) or post-pyloric (eg, J-tube) tubes: Crush and disperse tablet(s) in 60 mL purified water; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref). After administration, flush tube with an additional 20 mL of purified water (Ref). Although D5W has been studied as a diluent and may be used instead of purified water, use of D5W may present practical challenges for clinicians (Ref)
General guidance: Hold enteral nutrition during drug administration; flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Not e: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s032lbl.pdf#page=38, must be dispensed with this medication.
Atrial fibrillation: To reduce the risk of stroke and systemic embolism in adults with atrial fibrillation and no history of moderate to severe mitral stenosis.
Postoperative venous thromboprophylaxis following hip or knee replacement surgery: Prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in adults who have undergone hip or knee replacement surgery.
Venous thromboembolism: Treatment of DVT or PE in adults; to reduce the risk of recurrent DVT or PE in adults following initial therapy; treatment of venous thromboembolism (VTE) and reduction of recurrent VTE in pediatric patients from birth and older and after ≥5 days of initial anticoagulant treatment.
Atrial flutter; Heparin-induced thrombocytopenia (treatment); Left ventricular thrombus, treatment or prophylaxis; Venous thromboembolism prophylaxis in patients with multiple myeloma receiving immunomodulatory therapy who are at a higher risk for venous thromboembolism
Apixaban may be confused with axitinib
Apixaban is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) at increased risk of bleeding (eg, gastric antral vascular ectasia, recent significant spontaneous bleeding, severe uncontrolled hypertension, bleeding diathesis, impaired renal function) or as treatment for a first pulmonary embolus for >12 months or deep vein thrombosis for >6 months (without additional risk factors) (O’Mahony 2023).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (direct oral anticoagulants) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, kidney function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).
Substrate of BCRP, CYP1A2 (Minor), CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abciximab: May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk X: Avoid
Acalabrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Aducanumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with aducanumab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Alemtuzumab: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Alteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Anacaulase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Anagrelide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Anticoagulants: Apixaban may increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid
Antidepressants with Antiplatelet Effects: May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Apalutamide: May decrease serum concentration of Apixaban. Risk X: Avoid
Aspirin: May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Bromperidol: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
BuPROPion: May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Caplacizumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider Therapy Modification
Chloroprocaine (Systemic): Anticoagulants may increase adverse/toxic effects of Chloroprocaine (Systemic). Risk C: Monitor
Cilostazol: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Clarithromycin: May increase serum concentration of Apixaban. Risk C: Monitor
Collagenase (Systemic): Anticoagulants may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Apixaban. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Apixaban. Risk C: Monitor
Dabigatran Etexilate: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid
Dasatinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Deferasirox: Anticoagulants may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Defibrotide: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Deoxycholic Acid: Anticoagulants may increase adverse/toxic effects of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor
Donanemab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with donanemab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Edoxaban: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid
Enzalutamide: May decrease serum concentration of Apixaban. Management: Consider alternatives to this combination when possible. Apixaban serum concentrations and efficacy may be reduced. Risk D: Consider Therapy Modification
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may decrease therapeutic effects of Factor X (Human). Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of Apixaban. Management: Consider alternatives to this combination when possible. Apixaban dose adjustments may be required when used with systemic fusidic acid. Patients using this combination should be monitored extra closely. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Apixaban. Risk C: Monitor
Hemin: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase adverse/toxic effects of Anticoagulants. Bleeding may occur. Risk C: Monitor
Ibritumomab Tiuxetan: Anticoagulants may increase adverse/toxic effects of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor
Ibrutinib: Anticoagulants may increase adverse/toxic effects of Ibrutinib. Specifically, the risks of bleeding and hemorrhage may be increased. Risk C: Monitor
Icosapent Ethyl: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease serum concentration of Apixaban. Risk C: Monitor
Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease serum concentration of Apixaban. Risk X: Avoid
Inhibitors of CYP3A4 (Moderate) and P-glycoprotein: May increase serum concentration of Apixaban. Risk C: Monitor
Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Risk D: Consider Therapy Modification
Inotersen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Kanamycin: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Lecanemab: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Management: Avoid use of lecanemab in patients who are being treated with an anticoagulant when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
LevETIRAcetam: May decrease therapeutic effects of Apixaban. Risk C: Monitor
Limaprost: May increase adverse/toxic effects of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor
Lipid Emulsion (Fish Oil Based): May increase anticoagulant effects of Anticoagulants. Lipid Emulsion (Fish Oil Based) may decrease anticoagulant effects of Anticoagulants. Risk C: Monitor
Mesoglycan: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
MiFEPRIStone: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid
Miscellaneous Antiplatelets: May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Naproxen: May increase adverse/toxic effects of Apixaban. Specifically, the risk for bleeding may be increased. Naproxen may increase serum concentration of Apixaban. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and naproxen. If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Nintedanib: Anticoagulants may increase adverse/toxic effects of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Obinutuzumab: Anticoagulants may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Management: Consider avoiding coadministration of obinutuzumab and anticoagulants, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omacetaxine: Anticoagulants may increase adverse/toxic effects of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid
Omega-3 Fatty Acids: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Oritavancin: May decrease therapeutic effects of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor
Ozagrel: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of ozagrel and anticoagulants if possible. If coadministration is required, use caution, monitor patients closely for signs and symptoms of bleeding, and consider ozagrel or anticoagulant dose reductions. Risk D: Consider Therapy Modification
Pentosan Polysulfate Sodium: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Phenobarbital-Primidone: May decrease serum concentration of Apixaban. Risk C: Monitor
Pirtobrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Protein C Concentrate (Human): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Reteplase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Rivaroxaban: Anticoagulants may increase anticoagulant effects of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid
Salicylates: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
St John's Wort: May decrease serum concentration of Apixaban. Risk X: Avoid
Streptokinase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Sugammadex: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Sulodexide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Telavancin: May decrease therapeutic effects of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor
Tenecteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Tibolone: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Tipranavir: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Urokinase: May increase anticoagulant effects of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Valproic Acid and Derivatives: May decrease therapeutic effects of Apixaban. Risk C: Monitor
Vitamin E (Systemic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vitamin K Antagonists: Anticoagulants may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vorapaxar: May increase adverse/toxic effects of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid
Zanubrutinib: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
Grapefruit juice may increase levels/effects of apixaban. Management: Advise patients who consume grapefruit juice during therapy to use caution; monitor for increased effects (eg, bleeding).
Pregnancy planning is recommended for patients who could become pregnant and require use of direct-acting oral anticoagulants (DOACs). Outcome data related to the use of DOACs during pregnancy are limited; until safety data are available, adequate contraception is recommended during therapy for patients who may become pregnant. Patients planning to become pregnant should be switched to alternative anticoagulants prior to conception (Cohen 2016) or immediately once pregnancy is confirmed (Beyer-Westendorf 2021).
Heavy menstrual bleeding may occur in patients taking DOACs. Evaluate menstrual bleeding patterns prior to therapy in patients with underlying hemorrhagic conditions. Evaluate changes in uterine bleeding. Surgical interventions may be required in patients with abnormal uterine bleeding (Beyer-Westendorf 2021).
Based on placenta perfusion studies, apixaban is expected to cross the placenta (Bapat 2016).
Outcome data specific to the use of apixaban in pregnancy are limited (Areia 2022; Beyer-Westendorf 2016; Lameijer 2018; Sessa 2019). Use of direct-acting oral anticoagulants increases the risk of bleeding in all patients. When used in pregnancy, there is also the potential for fetal bleeding or subclinical placental bleeding which may increase the risk of miscarriage, preterm delivery, fetal compromise, or stillbirth (Cohen 2016).
Data are insufficient to evaluate the safety of direct-acting oral anticoagulants during pregnancy and use in pregnant patients is not recommended (ACOG 2018; ESC [Regitz-Zagrosek 2018]). Patients should be switched to an alternative anticoagulant if pregnancy occurs during therapy. Fetal monitoring that includes evaluations for fetal bleeding and assessments for risk of preterm delivery are recommended if the direct-acting oral anticoagulant is continued (Cohen 2016).
Data collection to monitor pregnancy and infant outcomes following exposure to direct-acting oral anticoagulants during pregnancy is ongoing. Health care providers may enroll patients in the international Registry of Pregnancy During DOAC Use (https://redcap.isth.org/surveys/?s=P99ARFCM3J) (Othman 2019).
Apixaban is present in breast milk.
• Breast milk was sampled from 1 lactating woman (23 months postpartum) following administration of 2 doses of apixaban 5 mg, administered 12 hours apart. Samples were obtained prior to then 3.5, 7, 12, 16, and 24 hours after the first dose. Average apixaban concentrations were 113.56 ng/mL (breast milk) and 43.58 ng/mL (maternal plasma). Authors of the study calculated the relative infant dose (RID) of apixaban to be 12.78% of the weight adjusted maternal dose (based on an average maternal weight of 75 kg), providing an estimated infant dose via breast milk of 0.017 mg/kg/day (Zhao 2020).
• The presence of apixaban in breast milk was evaluated in 3 lactating patients following administration of apixaban 5 mg twice daily for 3 to 12 days. Samples were obtained from 0 to 12 hours after a dose. The maximum apixaban breast milk concentrations were 200 to 250 ng/mL occurring 1 to 2 hours after dosing. Average breast milk concentrations were 134 to 150 ng/mL. Authors of the study calculated the RID of apixaban to be 14% to 21% of the weight adjusted maternal dose, providing an estimated infant dose via breast milk of 0.01 mg/kg per 12 hours (Datta 2021).
• In general, breastfeeding is considered acceptable when the RID of a medication is <10%; when the RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Additional considerations can include the gestational and postnatal age of the infant, the actual amount of milk being ingested (less in the first couple days of life and when weaning), properties of the specific maternal medication, medical conditions of the infant, and medications the infant is receiving therapeutically.
Breastfeeding is not recommended by the manufacturer. Until safety data are available, direct acting oral anticoagulants are not recommended for use in patients who are breastfeeding; use of an alternative anticoagulant is preferred (ACOG 2018; ASH [Bates 2018]; Cohen 2016).
CBC, aPTT, PT, serum creatinine, and liver function tests prior to initiation, when clinically indicated, and at least annually (ACC/AHA [Joglar 2024]; Leung 2023).
Routine coagulation testing is not required or necessary for direct oral anticoagulants (DOACs). There are currently no FDA-approved assays or calibration reagents available.
In clinical situations when assessment of the anticoagulant effect is useful (eg, acute care, periprocedural settings, absorption), evaluating a recent creatinine clearance and time since the last dose was ingested is usually sufficient for guiding clinical decisions. No commonly used coagulation tests can definitively exclude the presence of clinically relevant serum concentrations. A prolonged PT suggests clinically relevant serum concentrations are present, but normal PT and aPTT values cannot rule out the presence of apixaban.
If available, the preferred test to rule out clinically significant serum concentrations and quantify anticoagulant effect is anti-factor Xa activity calibrated specifically for apixaban (undetectable anti-factor Xa activity likely excludes clinically relevant drug concentrations). An anti-factor Xa assay calibrated for low molecular weight heparin can rule out clinically relevant drug concentrations, but is not useful for quantification (ACC [Tomaselli 2020]; AHA [Raval 2017]; Leung 2023).
When converting from apixaban to a vitamin K antagonist (VKA), it has been recommended to perform INR testing just prior to each dose of apixaban beginning on day 3 of concurrent therapy with the VKA (Eliquis Canadian product monograph).
In patients receiving apixaban therapy during neuraxial anesthesia (epidural or spinal anesthesia) or spinal/epidural puncture, monitor frequently for signs and symptoms of neurologic impairment (eg, numbness/weakness of legs, bowel/bladder dysfunction).
The International Council for Standardization in Haematology (ICSH) provides examples of apixaban drug levels for the 5 mg twice-daily dose, with an expected median peak of ~132 to 171 ng/mL (5th to 95th percentile of 59 to 321 ng/mL) and an expected median trough of ~63 to 103 ng/mL (5th to 95th percentile, 22 to 230 ng/mL) (Gosselin 2018). These values are intended to be used as guides to provide evidence of drug absorption, not as therapeutic targets (Leung 2023).
Inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound factor Xa (FXa). FXa, as part of the prothrombinase complex consisting also of factor Va, calcium ions, and phospholipid, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin.
Onset: 3 to 4 hours
Distribution: Vss: ~21 L
Protein binding: ~87%
Metabolism: Hepatic predominantly via CYP3A4/5 and to a lesser extent via CYP1A2, 2C8, 2C9, 2C19, and 2J2 to inactive metabolites; O-demethylation and hydroxylation are the major sites of transformation; substrate of P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)
Bioavailability: ~50%
Half-life elimination: ~12 hours (8 to 15 hours) (AHA [Raval 2017])
Time to peak: 3 to 4 hours
Excretion: Urine (~27% as parent drug); feces (biliary and direct intestinal excretion)
Altered kidney function: In subjects with ESRD, the AUC of apixaban was 17% greater compared to those with normal kidney function.
Older adult: Systemic exposure is increased ~32% in patients >65 years of age.
