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Apixaban

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
Brands: Eliquis

Medically reviewed by Drugs.com on Oct 14, 2019. Written by ASHP.

Warning

    Risk of Thrombosis Following Premature Discontinuance of Anticoagulation
  • Premature discontinuance of any oral anticoagulant, including apixaban, increases risk of thrombotic events.

  • If discontinuance is required for reasons other than pathologic bleeding or completion of a course of therapy, consider coverage with an alternative anticoagulant. (See Risk of Thrombosis Following Premature Discontinuance of Anticoagulation under Cautions.)

    Spinal/Epidural Hematoma
  • Risk of epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, in patients who are anticoagulated and also receiving neuraxial (spinal/epidural) anesthesia or spinal puncture.

  • Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet-aggregation inhibitors, other anticoagulants).

  • Risk also increased by history of traumatic or repeated epidural or spinal puncture, spinal deformity, or spinal surgery.

  • Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.

  • Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for anticoagulant therapy. (See Spinal/Epidural Hematoma under Cautions.)

Introduction

Anticoagulant; an oral, reversible, direct activated factor X (factor Xa) inhibitor.

Uses for Apixaban

Embolism Associated with Atrial Fibrillation

Reduction in the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

More effective than aspirin or warfarin in reducing the risk of stroke and systemic embolism, major bleeding, and all-cause mortality in such patients.

The American College of Chest Physicians (ACCP), American Stroke Association (ASA), ACC, AHA, and other experts currently recommend that antithrombotic therapy be given to all patients with nonvalvular atrial fibrillation (i.e., atrial fibrillation in the absence of rheumatic mitral stenosis, a prosthetic heart valve, or mitral valve repair) who are considered to be at increased risk of stroke, unless contraindicated.

Antithrombotic therapy in patients with atrial flutter generally managed in the same manner as in patients with atrial fibrillation.

Choice of antithrombotic therapy is based on patient's risk for stroke and bleeding. In general, oral anticoagulant therapy is recommended in patients with moderate to high risk for stroke and acceptably low risk of bleeding, while aspirin or no antithrombotic therapy may be considered in patients at low risk of stroke. Patients considered to be at increased risk of stroke generally include those with prior ischemic stroke or TIA, advanced age (e.g., ≥75 years), history of hypertension, diabetes mellitus, or CHF. In addition, female sex is considered an important risk factor for stroke in patients with atrial fibrillation, particularly in patients ≥75 years of age.

Apixaban is recommended by some experts as a useful alternative to warfarin in patients at moderate to high risk of stroke who are unable to comply with warfarin monitoring requirements or in whom a consistent therapeutic response to warfarin cannot be achieved; warfarin may still be preferred in patients who have well-controlled INRs and are compliant with regular laboratory monitoring.

Relative efficacy and safety of apixaban and other non-vitamin K antagonist oral anticoagulants (e.g., dabigatran, rivaroxaban) remains to be fully elucidated.

AHA and ASA state that apixaban, dabigatran, or rivaroxaban may be a useful alternative to warfarin for the prevention of stroke and systemic thromboembolism in selected women with paroxysmal or permanent atrial fibrillation and certain risk factors who do not have a prosthetic heart valve or hemodynamically important valve disease, severe renal failure (Clcr <15 mL/minute), lower body weight (<50 kg), or advanced liver disease (impaired baseline clotting function).

When selecting an appropriate anticoagulant, consider factors such as individual patient's risks of stroke and bleeding; patient compliance, preference, and comorbidities; cost; availability of agents to reverse anticoagulant effects in case of bleeding complications; availability of facilities to monitor INR; and degree of current INR control in patients already receiving warfarin.

Manufacturer states that apixaban not recommended in patients with prosthetic heart valves.

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.

More effective than sub-Q enoxaparin sodium 40 mg once daily in reducing risk of venous thromboembolism with similar rates of bleeding. 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) not established.

ACCP and other clinicians consider apixaban an acceptable option for pharmacologic thromboprophylaxis in patients undergoing total hip- or knee-replacement surgery; however, a low molecular weight heparin (LMWH) generally is preferred. Apixaban may be a reasonable choice when an LMWH is not available or cannot be used.

Data currently lacking on efficacy and safety of apixaban thromboprophylaxis in patients undergoing hip-fracture surgery.

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, bleeding risk, logistics, and compliance.

Treatment and Secondary Prevention of DVT and/or PE

Treatment and reduction in the risk of recurrence (secondary prevention) of acute DVT and/or PE.

For treatment of symptomatic acute DVT and/or PE, efficacy appears similar to conventional anticoagulant therapy (sub-Q enoxaparin followed by warfarin therapy adjusted to INR of 2–3 for 6 months) with lower incidence of major bleeding.

For secondary prevention following 6–12 months of initial anticoagulant therapy (e.g., with apixaban or enoxaparin and warfarin therapy), extended therapy with apixaban reduced incidence of symptomatic recurrent venous thromboembolism without increasing rate of major bleeding.

Limited data on efficacy and safety in patients with cancer, low body weight (<60 kg), or renal insufficiency (Clcr <50 mL/minute); additional study required.

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

Thromboprophylaxis in Acute Medical Illness

Current evidence in patients with acute medical illness suggests that extended treatment with apixaban (2.5 mg twice daily for 30 days) is not superior to short-term sub-Q enoxaparin sodium (40 mg once daily for 6–14 days) and is associated with an increased risk of major bleeding.

Acute Coronary Syndrome

Current evidence suggests that addition of apixaban to standard antiplatelet therapy (e.g., aspirin, clopidogrel) in patients with acute coronary syndrome (ACS) is associated with an increased risk of major (sometimes fatal) bleeding without substantial reduction in recurrent ischemic events.

Apixaban Dosage and Administration

General

  • Routine monitoring of coagulation tests not required.

  • Coagulation tests such as aPTT, PT, INR, and the Heptest (used to measure inhibition of exogenous factor Xa) generally not useful because of variable and inconsistent results.

  • A chromogenic anti-factor Xa assay (Rotachrom Heparin chromogenic assay) has been used to measure factor Xa activity; however, not recommended by manufacturer for assessing anticoagulant effects of apixaban.

Administration

Oral Administration

Administer orally twice daily with or without food.

In patients who are unable to swallow whole tablets, may 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. Alternatively, may 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. (See Extemporaneous Suspensions under Stability.)

If a dose is missed, take as soon as possible on the same day, then resume regular schedule; do not double dose to compensate for a missed dose.

Dosage

Adults

Embolism Associated with Atrial Fibrillation
Oral

5 mg twice daily.

Reduce dosage to 2.5 mg twice daily in patients with ≥2 of the following characteristics: age ≥80 years, body weight ≤60 kg, Scr ≥1.5 mg/dL. (See Special Populations under Dosage and Administration.)

Thromboprophylaxis in Hip- or Knee-Replacement Surgery
Oral

2.5 mg twice daily.

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

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

In clinical studies, initial dose was administered 12–24 hours after wound closure; treatment was continued postoperatively for 10–14 days after knee-replacement surgery and for 32–38 days after hip-replacement surgery.

Treatment and Secondary Prevention of DVT/PE
Oral

Acute treatment: 10 mg twice daily for 7 days, then 5 mg twice daily; therapy continued for 6 months in principal efficacy trial.

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

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). (See Drugs Affecting P-gp and CYP3A4 under Interactions.)

Patients receiving apixaban 2.5 mg twice daily: Avoid concomitant use with potent dual inhibitors of CYP3A4 and P-gp. (See Drugs Affecting P-gp and CYP3A4 under Interactions.)

Transitioning to Apixaban from Warfarin
Oral

Discontinue warfarin and initiate apixaban as soon as INR <2.

Transitioning to Warfarin from Apixaban
Oral

INR measurements may not be useful in determining appropriate dosage of warfarin because apixaban can also prolong INR. If continuous anticoagulation is necessary, may discontinue apixaban and simultaneously initiate a parenteral anticoagulant and warfarin at the time of the next scheduled dose of apixaban; discontinue parenteral anticoagulant once acceptable INR achieved.

Other strategies for transitioning from apixaban to warfarin based on patient’s Clcr and warfarin start date suggested.

Transitioning to and from Therapy with Anticoagulants Other than Warfarin
Oral

Discontinue anticoagulant currently being taken, and initiate the other anticoagulant at the time of the next scheduled dose.

Managing Anticoagulation in Patients Requiring Invasive Procedures

Temporarily interrupt apixaban therapy prior to elective surgery or other invasive procedure. For procedures associated with a moderate to high risk of unacceptable or clinically important bleeding, discontinue ≥48 hours prior to the procedure. For procedures associated with a low risk of bleeding or bleeding in a noncritical location that can be easily controlled, discontinue ≥24 hours prior to the procedure.

Bridging anticoagulation generally not required prior to procedure or during 24–48 hours after stopping apixaban.

Resume therapy after procedure as soon as adequate hemostasis established; although experience limited, some experts suggest that timing of resumption be based on procedural bleeding risk and hemostasis.

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild hepatic impairment (Child-Pugh class A). Because of limited experience, manufacturer states dosage recommendations cannot be provided in patients with moderate hepatic impairment (Child-Pugh class B). Use not recommended in patients with severe hepatic impairment (Child-Pugh class C). (See Hepatic Impairment under Cautions.)

Renal Impairment

Reduction of risk of stroke and systemic embolism in 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 (recommendation based on pharmacokinetic data; clinical efficacy and safety studies lacking). Reduce dosage to 2.5 mg twice daily in patients with Scr ≥1.5 mg/dL if they have at least one of the following additional characteristics: age ≥80 years or body weight ≤60 kg. (See Renal Impairment under Cautions.)

Prevention of DVT and associated PE following hip- or knee-replacement surgery or treatment or secondary prevention of DVT or PE: No dosage adjustment needed for patients with renal impairment including patients with ESRD who are maintained on intermittent hemodialysis. Dosage based on pharmacokinetic data; clinical efficacy and safety studies lacking.

Geriatric Patients

Manufacturer states that dosage adjustment based solely on age not necessary. 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: Scr ≥1.5 mg/dL or body weight ≤60 kg.

Body Weight

Manufacturer states that dosage adjustment based solely on body weight not necessary. 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 Scr ≥1.5 mg/dL.

Race/Ethnicity

No dosage adjustment necessary.

Cautions for Apixaban

Contraindications

  • Active pathologic bleeding.

  • Severe hypersensitivity reaction to apixaban.

Warnings/Precautions

Warnings

Risk of Thrombosis Following Premature Discontinuance of Anticoagulation

Premature discontinuance of any oral anticoagulant, including apixaban, increases risk of thromboembolic events in the absence of adequate alternative anticoagulation. (See Boxed Warning.)

Increased risk of stroke was observed during transition from apixaban to warfarin in clinical trials in patients with atrial fibrillation. Such patients generally had been switched to warfarin without a period of concurrent warfarin and apixaban therapy and thus were not adequately anticoagulated after stopping apixaban until a therapeutic INR with warfarin had been obtained.

If discontinuance of apixaban is required for reasons other than pathologic bleeding (e.g., prior to surgery or other invasive procedures) or completion of a course of therapy, consider coverage with an alternative anticoagulant. Important to ensure continuous anticoagulation during transition to alternative anticoagulant while minimizing risk of bleeding. Particular caution advised when switching from a factor Xa inhibitor to warfarin therapy because of warfarin's slow onset of action. (See Dosage under Dosage and Administration.)

Advise patients regarding importance of adhering to therapeutic regimen and on steps to take if doses are missed. (See Advice to Patients.)

Spinal/Epidural Hematoma

Epidural or spinal hematoma reported with concurrent use of anticoagulants and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures. Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis. (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. If traumatic puncture occurs, delay apixaban administration for 48 hours.

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

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., skin rash, allergic edema, anaphylactic reactions) reported. (See Contraindications under Cautions.)

Other Warnings and Precautions

Bleeding

Apixaban increases risk of hemorrhage and can cause serious, sometimes fatal, bleeding. Discontinue if active pathologic hemorrhage occurs. (See Contraindications under Cautions.) However, should not readily discontinue anticoagulation for commonly occurring minor or “nuisance” bleeding. (See Risk of Thrombosis Following Premature Discontinuance of Anticoagulation under Cautions.)

Renal impairment or concomitant use of drugs that affect hemostasis (e.g., aspirin or other antiplatelet drugs, NSAIAs, fibrinolytics, heparin or other anticoagulants, SSRIs, SNRIs) or drugs that inhibit both P-gp and CYP3A4 may increase risk of bleeding. (See Interactions.)

Temporarily interrupt therapy prior to any elective surgery or other invasive procedure to reduce risk of bleeding. (See Managing Anticoagulation in Patients Requiring Invasive Procedures under Dosage and Administration.)

Factor Xa (recombinant), inactivated-zhzo (also known as andexanet alfa), a recombinant modified human factor Xa protein, is a specific reversal agent for the anticoagulant effects of apixaban. 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.

If serious bleeding occurs, discontinue apixaban and initiate appropriate treatment. Not expected to be dialyzable because of high plasma protein binding.

May consider use of procoagulant reversal agents such as PCC, anti-inhibitor coagulant complex (activated PCC), or factor VIIa (recombinant) for immediate reversal of anticoagulation; however, data from clinical studies are limited.

Protamine sulfate and vitamin K not expected to affect anticoagulant activity of apixaban, and no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) or systemic hemostatics (desmopressin, aprotinin [no longer commercially available in the US]).

If overdosage occurs, may consider use of activated charcoal to decrease plasma apixaban concentrations more rapidly.

Patients with Prosthetic Heart Valves

Safety and efficacy not established in patients with prosthetic heart valves; use not recommended in such patients.

Specific Populations

Pregnancy

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

Apixaban use during labor or delivery in women who are receiving neuraxial anaesthesia may result in epidural or spinal hematomas. (See Boxed Warning.)

Consider use of a shorter-acting anticoagulant as delivery approaches.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Effects of apixaban on the breast-fed infant or on milk production unknown. Manufacturer states breast-feeding during treatment with apixaban not recommended.

Pediatric Use

Safety and efficacy not established in patients <18 years of age.

Geriatric Use

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

Hepatic Impairment

Pharmacokinetics and pharmacodynamics (inhibition of factor Xa activity) not substantially altered in patients with mild or moderate hepatic impairment. (See Special Populations under Pharmacokinetics.) Patients with moderate hepatic impairment may have intrinsic coagulation abnormalities that can affect response to therapy; however, impact of this effect not clear.

Data lacking in patients with severe hepatic impairment; manufacturer recommends against use in such patients.

Renal Impairment

Pharmacokinetics and pharmacodynamic effects not substantially altered in patients with renal impairment. (See Special Populations under Pharmacokinetics.)

Race/Ethnicity

Pharmacokinetics were similar among patients of different ethnic origins (Caucasian, Asian, and African-American). (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Bleeding.

Interactions for Apixaban

Metabolized by CYP3A4/5, and to a lesser extent by CYP isoenzymes 1A2, 2C8, 2C9, 2C19, and 2J2.

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

Substrate of the efflux transporter P-gp, but does not substantially inhibit P-gp.

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.

Pharmacokinetic interactions unlikely with drugs metabolized by major CYP isoenzymes.

Drugs Affecting P-gp Transport

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

Drugs Affecting P-gp and CYP3A4

Combined P-gp and CYP3A4 inhibitors: Possible increased apixaban exposure, which may increase risk of bleeding. Reduce dosage if used concomitantly with a potent dual inhibitor of P-gp and CYP3A4; avoid use if patient already receiving reduced dosage. (See Dosage under Dosage and Administration and also see Specific Drugs under Interactions.)

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

Drugs Affecting Hemostasis

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

Specific Drugs

Drug

Interaction

Comments

Amiodarone

Efficacy and safety of apixaban not altered with concomitant use

Antifungals, azole (i.e., itraconazole, ketoconazole)

Possible increased exposure to apixaban and risk of bleeding; result of dual CYP3A4 and P-gp inhibiting effect by itraconazole or ketoconazole

Reduce apixaban dosage by 50% if patient receiving >2.5 mg twice daily; avoid concomitant use if patient already receiving 2.5 mg twice daily

Avoid concomitant use of ketoconazole and apixaban in patients with ≥2 of the following characteristics: age ≥80 years, body weight ≤60 kg, Scr ≥1.5 mg/dL

Aspirin

Increased bleeding risk observed

Pharmacokinetics of aspirin not substantially altered in healthy individuals

Atenolol

Pharmacokinetics of atenolol or apixaban not substantially altered in healthy individuals

Carbamazepine

Possible decreased exposure to apixaban and increased risk of stroke; result of dual CYP3A4 and P-gp inducing effect by carbamazepine

Avoid concomitant use

Clarithromycin

Possible increased exposure to apixaban and risk of bleeding; result of dual CYP3A4 and P-gp inhibiting effect by clarithromycin

Manufacturer states no dosage adjustment is necessary

Clopidogrel

Pharmacodynamic interaction not observed

Increased risk of bleeding observed in patients receiving apixaban in combination with aspirin and clopidogrel

Digoxin

Pharmacokinetics of digoxin not substantially altered in healthy individuals

Diltiazem

Moderate increase in systemic exposure and peak plasma concentrations of apixaban

Enoxaparin

No effect on pharmacokinetics of apixaban; additive effect on peak anti-factor Xa activity but considered to be modest

Famotidine

Pharmacokinetics of apixaban not substantially altered in healthy individuals

Fibrinolytics

Potential increased risk of hemorrhage

Heparin

Potential increased risk of hemorrhage

NSAIAs (e.g., naproxen)

Potential increased risk of hemorrhage with chronic use

Naproxen: Pharmacokinetics of naproxen not substantially altered in healthy individuals, but systemic exposure and peak plasma concentrations of apixaban were moderately increased; anti-factor Xa activity increased by about 50–60%

Phenytoin

Possible decreased exposure to apixaban and increased risk of stroke; result of dual CYP3A4 and P-gp inducing effect by phenytoin

Avoid concomitant use

Prasugrel

Pharmacokinetics of prasugrel or apixaban not substantially altered in healthy individuals

Rifampin

Substantially decreased exposure and peak plasma concentrations of apixaban, which may increase risk of stroke; result of dual CYP3A4 and P-gp inducing effect by rifampin

Avoid concomitant use

Ritonavir

Possible increased exposure to apixaban and risk of bleeding; result of dual CYP3A4 and P-gp inhibiting effect by ritonavir

Reduce apixaban dosage by 50% if patient receiving >2.5 mg twice daily; avoid concomitant use in patients already receiving 2.5 mg twice daily

SNRIs

Possible increased risk of hemorrhage

SSRIs

Possible increased risk of hemorrhage

St. John's wort (Hypericum perforatum)

Possible decreased exposure to apixaban and increased risk of stroke; result of dual CYP3A4 and P-gp inducing effect by St. John's wort

Avoid concomitant use

Apixaban Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 50%.

Following oral administration, peak plasma concentrations occur within approximately 3–4 hours.

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

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.

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.

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.

Food

Food does not appear to affect systemic exposure or peak plasma concentrations.

Distribution

Extent

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

Plasma Protein Binding

Approximately 87%.

Elimination

Metabolism

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

Elimination Route

Eliminated via multiple pathways, including hepatic metabolism and intestinal, biliary, and renal excretion; approximately 25% of an administered dose is eliminated renally. Total clearance approximately 3.3 L/hour.

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

Half-life

Clearance half-life approximately 6 hours, but apparent half-life longer (approximately 12 hours) following repeated administration because of prolonged absorption.

Special Populations

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

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

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

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

Stability

Storage

Extemporaneous Suspensions

Apixaban in water, dextrose 5% in water, apple juice, or applesauce (see Oral Administration under Dosage and Administration): Stable for ≤4 hours.

Oral

Tablets

20–25°C (may be exposed to 15–30°C).

Actions

  • Binds selectively and with high affinity to active site of factor Xa; inhibits free and clot-bound factor Xa and prothrombinase activity.

  • Inhibition of coagulation factor Xa prevents conversion of prothrombin to thrombin and subsequent thrombus formation.

  • Unlike fondaparinux, heparin, and LMWHs, apixaban blocks factor Xa directly and does not require a cofactor (antithrombin III) to exert its anticoagulant activity.

  • Inhibits factor Xa activity and prolongs PT, aPTT, and HepTest (an indirect measure of factor Xa activity) in a concentration-dependent manner.

Advice to Patients

  • Importance of taking the drug exactly as prescribed and not discontinuing therapy without first consulting a clinician. Importance of advising patients how to take the drug if they cannot swallow whole tablets or if they require a nasogastric tube.

  • Importance of advising 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; the missed dose should not be doubled.

  • Importance of informing 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; clinicians should advise patients on how to recognize signs and symptoms of bleeding. Importance of patients informing clinicians immediately about any unusual bleeding or bruising during therapy.

  • Importance of advising patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., numbness or weakness in legs, bowel or bladder dysfunction), particularly if they are receiving concomitant NSAIAs, platelet-aggregation inhibitors, or other anticoagulants; importance of patient immediately seeking emergency medical attention if any of these symptoms occur.

  • Importance of patients informing clinicians (e.g., physicians, dentists) that they are receiving apixaban therapy before scheduling any surgery or invasive procedures, including dental procedures.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians (e.g., physicians, dentists) of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements.

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

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.

Apixaban

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2.5 mg

Eliquis

Bristol-Myers Squibb

5 mg

Eliquis

Bristol-Myers Squibb

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 14, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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