Brand name: Eliquis
Drug class: Direct Factor Xa Inhibitors
Chemical name: 1H-Pyrazolo[3,4-c]pyridine-3-carboxamide,4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]
Molecular formula: C₂₅H₂₅N₅O₄
CAS number: 503612-47-3

Medically reviewed by Drugs.com on Mar 23, 2023. Written by ASHP.

Introduction

Anticoagulant; an oral, reversible, direct activated factor X (factor Xa) inhibitor.^{1 3 5 8 28 31 32 33 35 39 42}

Uses for Apixaban

Embolism Associated with Atrial Fibrillation

Reduction in the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.^{1 3 5 40 42 1007}

Direct oral anticoagulants (DOACs; apixaban, dabigatran, edoxaban, rivaroxaban) are noninferior or superior to warfarin in reducing thromboembolic risk in patients with nonvalvular atrial fibrillation (i.e., atrial fibrillation in the absence of moderate-to-severe mitral stenosis or a mechanical heart valve), and associated with reduced risk of serious bleeding.^{1 3 5 82 87}

The American College of Chest Physicians (ACCP), American Stroke Association (ASA), American College of Cardiology (ACC), American Heart Association (AHA), and other experts recommend antithrombotic therapy in all patients with nonvalvular atrial fibrillation who are considered to be at increased risk of stroke, unless contraindicated.^{80 81 82 87 989 990 999 1007 1017}

Current guidelines recommend use of the CHA₂DS₂-VASc risk stratification tool to assess a patient’s risk of stroke and need for anticoagulant therapy.^{82 989 1007}

Experts state that antithrombotic therapy generally is not necessary in low-risk patients (CHA₂DS₂-VASc score of 0 in males or 1 in females), but should be considered in all higher-risk patients.^{87 989 1007 1017}

In patients with nonvalvular atrial fibrillation who are eligible for oral anticoagulant therapy, DOACs are recommended over warfarin based on improved safety and similar or improved efficacy.^{82 87 989 1007}

Relative efficacy and safety of apixaban and other DOACs (e.g., dabigatran, rivaroxaban, edoxaban) remains to be fully elucidated.^{10 66 68 989 1017}

When selecting an appropriate anticoagulant, consider factors such as the absolute and relative risks of stroke and bleeding; costs; patient compliance, preference, tolerance, and comorbidities; and other clinical factors such as renal function and degree of international normalized ratio (INR) control (if the patient has been taking warfarin).^{80 81 82 83 84 989 1007}

Experts state that antithrombotic therapy in patients with atrial flutter generally should be managed in the same manner as in patients with atrial fibrillation.^{80 82 999 1007}

DOACs including apixaban have been used for pharmacologic cardioversion^{† [off-label]} in patients with atrial fibrillation or atrial flutter of >48 hours’ duration or of unknown duration; DOACs are recommended as an alternative to warfarin in this setting.^{87 1007}

Use of apixaban not recommended in patients with prosthetic heart valves; safety and efficacy not studied.¹

Thromboprophylaxis in Hip- or Knee-Replacement Surgery

Prevention of postoperative DVT, which may lead to PE, in patients who have undergone total hip- or knee-replacement surgery. ^{1 8 31 32 33 34 35 37 38 39 40 42 1003}

More effective than sub-Q enoxaparin sodium 40 mg once daily in reducing risk of venous thromboembolism (VTE) with similar rates of bleeding.^{1 32 33} Noninferiority of apixaban (2.5 mg twice daily) and currently recommended US dosing regimen for sub-Q enoxaparin sodium in knee-replacement surgery (30 mg twice daily)⁴⁷ not established.^{1 31}

Routine thromboprophylaxis is recommended in all patients undergoing major orthopedic surgery, including total hip- or knee-replacement surgery, because of the high risk of postoperative VTE.¹⁰⁰³

ACCP and other experts consider DOACs an acceptable option for pharmacologic thromboprophylaxis in patients undergoing total hip- or knee-replacement surgery.^{35 38 39 1003}

Drug selection and duration of therapy should be individualized based on type of surgery, patient risk factors for embolism and bleeding, costs, patient compliance, preference, tolerance, and comorbidities, and other clinical factors such as renal function.^{1003 1108}

Thromboprophylaxis in Acutely Ill Medical Patients

Has been used for VTE prevention in acutely ill medical patients^{† [off-label]}.⁵¹

Evidence suggests that extended treatment with apixaban is not superior to short-term treatment with sub-Q enoxaparin for thromboprophylaxis in patients with acute medical illness^{† [off-label]} and is associated with a small increased risk of major bleeding.⁵¹

American Society of Hematology (ASH) issued a strong recommendation to use low molecular weight heparins (LMWHs) instead of DOACs for VTE prophylaxis in acutely ill hospitalized medical patients, and also strongly recommends inpatient VTE prophylaxis with LMWH only rather than inpatient and extended-duration outpatient VTE prophylaxis with DOACs.¹¹¹⁶

Thromboprophylaxis in Cancer Patients

Patients with active cancer^{† [off-label]} are at increased risk for VTE; primary thromboprophylaxis with apixaban in this population may be beneficial but carries a bleeding risk.¹¹⁵⁷

American Society of Clinical Oncology (ASCO) guideline states that high-risk outpatients with cancer (Khorana score ≥2 prior to starting a new systemic chemotherapy regimen) may be offered thromboprophylaxis with apixaban, rivaroxaban, or a LMWH provided there are no significant risk factors for bleeding and no drug interactions.^{1102 1103}

American Society of Hematology (ASH) guideline suggests thromboprophylaxis with a DOAC (apixaban or rivaroxaban) in ambulatory cancer patients at intermediate to high risk for thrombosis.¹¹⁰³

Consider patient's individual risk for thrombosis and risk of bleeding when deciding whether to administer thromboprophylaxis.^{1102 1103}

Venous Thromboembolism – Treatment and Secondary Prevention

Treatment and reduction in the risk of recurrence (secondary prevention) of acute DVT and/or PE.^{1 43 44 45 46 48}

Not recommended as initial therapy (as an alternative to unfractionated heparin) in patients with PE who have hemodynamic instability or who may receive thrombolytic therapy or undergo pulmonary embolectomy.¹

Recommended by ACCP, ASH, and the Anticoagulation Forum as an acceptable option for initial and long-term anticoagulant therapy in patients with acute proximal DVT of the leg and/or PE.^{1006 1008 1106}

DOACs are among several anticoagulants that can be used for treatment of VTE.¹¹⁰⁶ DOACs have similar efficacy to warfarin, but reduced bleeding (particularly intracranial hemorrhage) and greater convenience for patients and healthcare providers.¹¹⁰⁶

DOACs generally should not be used in settings with high risk of bleeding (e.g., hemorrhagic lesion, renal/hepatic impairment, thrombocytopenia, GI or genitourinary malignancy, mucosal lesion, CNS malignancy or bleeding, recent surgery) or in patients with morbid obesity (body weight >120 kg or BMI ≥40 mg/m²), drug-drug interactions, or GI complications affecting oral therapy (e.g., poor absorption, nausea and vomiting) because of the lack of safety data.^{1102 1106}

In patients with cancer and established VTE, LMWHs or oral factor Xa inhibitors (e.g., apixaban, rivaroxaban, edoxaban) are generally recommended over warfarin for long-term anticoagulation.^{1102 1103 1106} ACCP and ASH recommend the use of an oral factor Xa inhibitor over LMWH for the initiation and treatment phases of therapy in patients with cancer-associated thrombosis.^{1103 1106}

Apixaban Dosage and Administration

General

Pretreatment Screening

• Prior to initiating therapy with apixaban, assess renal function.¹

• Obtain body weight and serum creatinine to determine dosage in patients with nonvalvular atrial fibrillation.¹

Patient Monitoring

• Periodically assess serum creatinine concentration as clinically indicated in patients with nonvalvular atrial fibrillation and adjust therapy accordingly.¹

• Periodically assess body weight in patients with nonvalvular atrial fibrillation at risk of decreasing to ≤60 kg.¹

• If apixaban is administered in an epidural or spinal anesthesia/analgesia or lumbar puncture setting, frequently monitor for signs or symptoms of neurological impairment (e.g., numbness, tingling, weakness in lower limbs, bowel and/or bladder dysfunction).¹

• Monitor patients for any signs or symptoms of bleeding (e.g., unusual bruising) during therapy.¹

• Routine coagulation monitoring (e.g., prothrombin time [PT], activated partial thromboplastin time [aPTT], international normalized ratio [INR]) is not necessary with apixaban therapy because of the drug's predictable pharmacokinetic and pharmacodynamic effects.^{8 19 22 30 40 989} However, in certain situations, such as in the case of overdosage or in patients with hemorrhagic or thromboembolic complications or those requiring emergency surgery, it may be useful to assess the degree of anticoagulation.^{8 19 22 40 42} Although apixaban produces concentration-dependent increases in aPTT, PT, INR, and the Heptest (used to measure inhibition of exogenous activated factor X [factor Xa]), these tests generally are not useful for monitoring the anticoagulant effects of apixaban because of a high degree of inconsistency and variability in results.^{1 8 19 28 40 42} A chromogenic anti-factor Xa assay (Rotachrom Heparin chromogenic assay) was used during the apixaban development program to measure the effect of apixaban on factor Xa activity.¹ Although the chromogenic assay appears to correlate well with apixaban activity and may produce less variable results than other coagulation tests, a standardized assay specifically calibrated for apixaban currently is not available in most healthcare facilities.^{1 19 28 40 42} The manufacturer does not recommend use of this chromogenic assay for assessing the anticoagulant effects of apixaban.¹

Dispensing and Administration Precautions

• Per the Institute for Safe Medication Practices (ISMP), apixaban is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.¹¹⁶⁹

Oral Administration

Administer orally twice daily with or without food.¹

In patients unable to swallow whole tablets, crush apixaban 2.5- or 5-mg tablets and suspend in water, 5% dextrose in water, or apple juice, or mix with applesauce and promptly administer orally.¹ Alternatively, crush apixaban 2.5- or 5-mg tablets, suspend in 60 mL of water or 5% dextrose in water, and promptly deliver through a nasogastric feeding tube.¹

If a dose is missed, take as soon as possible on the same day, then resume regular schedule.¹ Do not double dose to make up for missed dose.¹

Dosage

Adults

Embolism Associated with Atrial Fibrillation

Oral

5 mg twice daily.¹

Reduce dosage to 2.5 mg twice daily in patients with ≥2 of the following characteristics: age ≥80 years, body weight ≤60 kg, S_cr ≥1.5 mg/dL.^{1 42}

Thromboprophylaxis in Hip- or Knee-Replacement Surgery

Oral

2.5 mg twice daily.¹

Administer first dose ≥12–24 hours after surgery, provided hemostasis has been established.¹

Duration of therapy: Manufacturer recommends 35 days for patients undergoing hip-replacement surgery, 12 days for patients undergoing knee-replacement surgery.¹

Venous Thromboembolism - Treatment and Secondary Prevention

Oral

Acute treatment: 10 mg twice daily for 7 days, then 5 mg twice daily;^{1 43 44} therapy continued for 6 months in principal efficacy trial.^{43 44}

Extended treatment (to reduce DVT/PE recurrence following ≥6 months of initial anticoagulant therapy): 2.5 mg twice daily.^{1 45 46}

Determine optimum duration of anticoagulation based on individual clinical situation.¹⁰⁰⁵ In general, ACCP states that anticoagulant therapy for VTE should be continued beyond the acute treatment period for at least 3 months, and possibly longer in certain patients with a high risk of recurrence and low or moderate risk of bleeding.¹⁰⁰⁵

Coadministration with Dual Inhibitors of CYP3A4 and P-glycoprotein (P-gp)

Oral

Patients receiving >2.5 mg apixaban twice daily: Reduce dosage by 50% (e.g., from 5 mg twice daily to 2.5 mg twice daily) in patients receiving concomitant therapy with potent inhibitors of both CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir).¹

Patients receiving apixaban 2.5 mg twice daily: Avoid concomitant use with potent dual inhibitors of CYP3A4 and P-gp.¹

Transitioning from Other Anticoagulants

Transitioning from warfarin to apixaban: Discontinue warfarin and initiate apixaban as soon as INR <2.¹

Transitioning from other anticoagulants to apixaban: Discontinue current anticoagulant and initiate apixaban at the time of the next scheduled dose of the other anticoagulant.¹

Transitioning to Other Anticoagulants

Transitioning from apixaban to warfarin: INR measurements may not be useful because apixaban can prolong INR.¹ Discontinue apixaban and initiate a parenteral anticoagulant and warfarin simultaneously at the time of next scheduled apixaban dose; discontinue parenteral anticoagulant once a stable INR ≥2 is reached.¹

Transitioning from apixaban to other anticoagulants, including parenteral anticoagulants or other direct oral anticoagulants (DOACs): Discontinue apixaban and initiate other anticoagulant at the time of next scheduled apixaban dose.¹

Managing Anticoagulation in Patients Requiring Invasive Procedures

Temporarily discontinue apixaban therapy at least 24 hours prior to procedures associated with a low risk of bleeding or bleeding in a noncritical location that can be easily controlled or at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding.^{1 18 68}

If surgery cannot be delayed, weigh increased risk of bleeding against urgency of intervention.¹

Resume therapy postoperatively as soon as adequate hemostasis established;¹ although experience limited, some experts suggest that timing of resumption be based on procedural bleeding risk and hemostasis.^{18 68}

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild hepatic impairment (Child-Pugh class A).¹

Because of limited experience, manufacturer states dosage recommendations cannot be provided in patients with moderate hepatic impairment (Child-Pugh class B).^{1 77}

Use not recommended in patients with severe hepatic impairment (Child-Pugh class C).¹

Renal Impairment

Patients with nonvalvular atrial fibrillation: Manufacturer states that dosage adjustment based solely on renal function (including patients with end-stage renal disease [ESRD] on intermittent hemodialysis) not necessary.^{1 77} Reduce dosage to 2.5 mg twice daily in patients with S_cr ≥1.5 mg/dL if they have at least one of the following additional characteristics: age ≥80 years or body weight ≤60 kg.¹

Patients receiving apixaban for thromboprophylaxis following orthopedic surgery or for treatment of VTE: No dosage adjustment needed for patients with renal impairment including patients with ESRD on intermittent hemodialysis.¹

Geriatric Patients

Dosage adjustment based solely on age not necessary.¹ Reduce dosage to 2.5 mg twice daily in geriatric patients ≥80 years of age with nonvalvular atrial fibrillation if they have at least one of the following additional characteristics: S_cr ≥1.5 mg/dL or body weight ≤60 kg.¹

Body Weight

Dosage adjustment based solely on body weight is not necessary.¹ Reduce dosage to 2.5 mg twice daily in patients with nonvalvular atrial fibrillation who weigh ≤60 kg if they have at least one of the following additional characteristics: age ≥80 years or S_cr ≥1.5 mg/dL.¹

Cautions for Apixaban

Contraindications

• Active pathologic bleeding.¹

• Severe hypersensitivity reaction to apixaban.¹

Warnings/Precautions

Warnings

Risk of Thrombosis Following Premature Discontinuance of Anticoagulation

Premature discontinuance in the absence of adequate alternative anticoagulation may increase risk of thromboembolic events.¹ (See Boxed Warning.)

When transitioning patients from one anticoagulant therapy to another, ensure continuous anticoagulation while minimizing risk of bleeding.⁸³ Particular caution advised when switching from a factor Xa inhibitor to warfarin therapy because of warfarin's slow onset of action.⁸³

If discontinuance of apixaban is required for reasons other than pathologic bleeding or completion of a course of therapy, consider coverage with an alternative anticoagulant.¹

Spinal/Epidural Hematoma

Epidural or spinal hematoma reported with concurrent use of anticoagulants and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.¹ Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis.¹ (See Boxed Warning.)

Delay removal of indwelling epidural or intrathecal catheters for ≥24 hours after a dose of apixaban and wait ≥5 hours after catheter removal before administering next dose.¹ If traumatic puncture occurs, delay apixaban administration for 48 hours.¹

Frequently monitor for signs of neurologic impairment (e.g., numbness or weakness in lower limbs, bowel or bladder dysfunction).¹ If neurologic compromise noted, diagnose and treat immediately.¹ Carefully consider potential benefits versus risks of neuraxial intervention in patients who are currently receiving or will receive anticoagulants.¹

Other Warnings and Precautions

Bleeding

Risk of serious, potentially fatal, bleeding.^{1 3 5 18 19 21} Promptly evaluate if any manifestations of blood loss occur during therapy.¹

Discontinue if active pathologic bleeding occurs.¹ However, should not readily discontinue anticoagulation for commonly occurring minor or “nuisance” bleeding.⁸³

Risk of bleeding may be increased in patients with renal impairment or those receiving concomitant drugs that affect hemostasis (e.g., aspirin or other antiplatelet drugs, NSAIAs, fibrinolytics, heparin or other anticoagulants, SSRIs, SNRIs); drugs that inhibit both P-gp and CYP3A4 may also increase risk of bleeding.^{1 6 42}

Temporarily interrupt therapy prior to any elective surgery or other invasive procedure to reduce risk of bleeding.¹

If serious bleeding occurs, discontinue apixaban and initiate appropriate treatment.^{1 13 22 989}

Factor Xa (recombinant), inactivated-zhzo (also known as andexanet alfa) is a specific reversal agent for the anticoagulant effects of apixaban.^{90 91 92} Safety of factor Xa (recombinant), inactivated-zhzo not established in patients who have experienced a thromboembolic event or disseminated intravascular coagulation (DIC) within 2 weeks prior to the life-threatening bleeding event requiring treatment with the drug or in those who have received prothrombin complex concentrates (PCC), recombinant factor VIIa, or whole blood products ≤7 days prior to the bleeding event.⁹⁰

May consider use of procoagulant reversal agents such as 4-factor PCC for immediate reversal of anticoagulation if factor Xa (recombinant), inactivated-zhzo is not available;⁴³ however, data from clinical studies are limited.^{1 13 19 43}

Protamine sulfate, vitamin K, and tranexamic acid not expected to be effective.¹ Not expected to be dialyzable.¹

If overdosage occurs, may consider use of activated charcoal to decrease plasma apixaban concentrations more rapidly.^{1 19}

Patients with Prosthetic Heart Valves

Efficacy and safety not established; use generally not recommended.¹

Patients with Pulmonary Embolism

Avoid use as initial therapy in pulmonary embolism patients who have hemodynamic instability or who may receive thrombolytic therapy or undergo pulmonary embolectomy.¹

Thrombosis Risk in Triple-Positive Antiphospholipid Syndrome

Risk of recurrent thrombotic events in patients with triple-positive antiphospholipid syndrome (APS) (i.e., positive for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies); use not recommended in these patients.¹

Specific Populations

Pregnancy

No adequate data in pregnant women; increased maternal bleeding observed in animals.¹

Use during labor and delivery in women receiving neuraxial anaesthesia may result in epidural or spinal hematomas.¹

Consider use of a shorter-acting anticoagulant as delivery approaches.¹ Monitor for increased bleeding in the neonate.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹

Unknown effects on the breast-fed infant or on milk production.¹ Discontinue nursing or the drug.¹

Females and Males of Reproductive Potential

Assess for increased risk of bleeding potentially requiring surgical intervention in females of reproductive potential and those with abnormal uterine bleeding.¹

Pediatric Use

Safety and efficacy not established.^{1 3 4}

Geriatric Use

No substantial differences in efficacy and safety relative to younger adults.¹

Hepatic Impairment

Mild-to-moderate hepatic impairment (Child-Pugh class A and B) does not appear to affect anti-factor Xa activity.¹ However, impact of moderate hepatic impairment on the coagulation cascade and relationship to efficacy and bleeding not known.¹ Response to therapy may be affected in patients with moderate hepatic impairment.¹

No clinical experience in patients with severe hepatic impairment (Child-Pugh class C); do not use.¹

Renal Impairment

Pharmacokinetic and pharmacodynamic effects not substantially altered in patients with renal impairment.¹

Race/Ethnicity

Similar pharmacokinetics among patients of different ethnic origins (Caucasian, Asian, and African-American).^{1 8 42}

Common Adverse Effects

Common adverse reactions (>1%): Bleeding.^{1 3 5}

Drug Interactions

Metabolized by cytochrome P-450 (CYP) 3A4/5, and to a lesser extent by CYP isoenzymes 1A2, 2C8, 2C9, 2C19, and 2J2.^{1 15}

Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 3A4/5, or 2C19 nor induce CYP isoenzymes 1A2, 2B6, or 3A4/5.^{1 15 16}

Substrate of CYP3A4, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP3A4/5: Although pharmacokinetic interactions are possible, potential may be low because of apixaban’s multiple routes of elimination.^{8 15 35 77}

Pharmacokinetic interactions unlikely with drugs metabolized by major CYP isoenzymes.^{1 15 16}

Drugs Affecting P-gp Transport

Inhibitors or inducers of P-gp: Potential pharmacokinetic interaction.¹

Drugs Affecting P-gp and CYP3A4

Combined P-gp and CYP3A4 inhibitors: Possible increased apixaban exposure, which may increase risk of bleeding.¹ Reduce dosage if used concomitantly with a potent dual inhibitor of P-gp and CYP3A4; avoid use if patient already receiving reduced dosage.¹

Combined P-gp and CYP3A4 inducers: Possible decreased apixaban exposure, which may increase risk of stroke.¹ Avoid concomitant use with potent dual inducers of P-gp and CYP3A4.¹

Drugs Affecting Hemostasis

Potential increased risk of hemorrhage.¹ Promptly evaluate any manifestations of bleeding.¹

Specific Drugs

Apixaban Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 50%.^{1 17 28}

Following oral administration, peak plasma concentrations occur within approximately 3–4 hours.^{1 17 28}

Absorption occurs throughout GI tract; about 55% of dose absorbed in distal small intestine and ascending colon.¹

Following oral administration of 10 mg of apixaban as 2 crushed 5-mg tablets suspended in 30 mL of water, bioavailability is similar to that after 2 intact 5-mg tablets taken orally.¹

Following oral administration of 10 mg of apixaban as 2 crushed 5-mg tablets mixed with 30 g of applesauce, the peak plasma concentration and bioavailability of apixaban are decreased by 20 and 16%, respectively.¹

Following administration via nasogastric feeding tube of a single, crushed 5-mg tablet suspended in 60 mL of 5% dextrose in water, bioavailability of the drug is similar to that of a whole tablet taken orally.¹

Food

Food does not appear to affect systemic exposure or peak plasma concentrations.^{1 17}

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.¹

Plasma Protein Binding

Approximately 87%.^{1 28}

Elimination

Metabolism

Metabolized principally by CYP3A4/5 with minor contributions from CYP isoenzymes 1A2, 2C8, 2C9, and 2J2.^{1 15} No active circulating metabolites.¹

Elimination Route

Eliminated via multiple pathways, including hepatic metabolism and intestinal, biliary, and renal excretion; approximately 25% of an administered dose is eliminated renally.^{1 15 16 42 77} Total clearance approximately 3.3 L/hour.¹

Not expected to be removed by dialysis due to high plasma protein binding.¹

Half-life

Approximately 12 hours (8–15 hours).^{1 1161}

Special Populations

Systemic exposure and peak plasma concentrations not substantially altered in patients with mild or moderate hepatic impairment.¹

Systemic exposure and peak plasma concentrations not substantially altered in patients with mild, moderate, or severe renal impairment.¹

Systemic exposure and peak plasma concentrations are similar in patients ≥65 years of age and younger adults (18–40 years of age).¹

Peak plasma concentrations, half-life, and time to steady-state are similar among patients of different ethnic origins (e.g., Caucasian, Asian, African-American).^{1 8 42}

Stability

Storage

Extemporaneous Suspensions

Apixaban in water, dextrose 5% in water, apple juice, or applesauce: Stable for ≤4 hours.¹

Oral

Tablets

20–25°C (excursions permitted to 15–30°C).¹

Actions

• Binds directly and selectively to factor Xa; inhibits free and clot-bound factor Xa and prothrombinase activity.^{1 38 42}

• Inhibition of coagulation factor Xa prevents prothrombin to thrombin conversion and subsequent thrombus formation.^{1 28 42}

• Does not require a cofactor (antithrombin III) to exert anticoagulant activity.^{1 38 42}

• Inhibits factor Xa activity and prolongs PT, aPTT, and HepTest in a concentration-dependent manner.^{1 8 28}

Advice to Patients

• Take apixaban exactly as prescribed and do not discontinue therapy without first consulting a clinician.¹

• Advise patients on how to take the drug if they cannot swallow whole tablets or if they require a nasogastric tube.¹

• Instruct patients that if a dose is missed, to take it as soon as possible on the same day and then resume the regular twice-daily dosing schedule; do not take 2 doses at the same time.¹

• Inform patients that they may bruise and/or bleed more easily and that a longer than normal time may be required to stop bleeding when taking apixaban; advise patients on how to recognize signs and symptoms of bleeding.¹

• Inform clinicians immediately about any unusual bleeding or bruising during therapy, including menstrual or vaginal bleeding that is heavier than normal.¹

• Apixaban is generally not for patients with artificial heart valves; advise patients to inform their health care provider if they have had or will have heart valve surgery.¹

• Apixaban is not recommended for use in people with antiphospholipid syndrome (APS), especially with positive triple antibody testing; advise patients to inform their healthcare provider if they have APS.¹

• Advise patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., numbness or weakness of legs, bowel or bladder dysfunction), particularly if they are receiving concomitant nonsteroidal anti-inflammatory agents (NSAIAs), platelet inhibitors, or other anticoagulants; inform the patient to seek emergency medical attention if any of these symptoms occur.¹

• Advise patients to inform clinicians (e.g., physicians, dentists) that they are receiving apixaban therapy before scheduling any surgery or invasive procedures, including dental procedures.¹

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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