Apixaban ELIQUIS Checklist

CLOT
Is Apixaban (Eliquis®) an Option for Your Patient?
Prior to prescribing, please review the following information
1
Indications
 Non-Valvular Atrial Fibrillation (NVAF)* to prevent stroke & systemic embolism
 Prevention of venous thromboembolic events (VTE) in total hip or knee replacement surgery (THR, TKR)
 VTE treatment & prevention [for deep vein thrombosis (DVT) and pulmonary embolism (PE)]
* CCS definition: Afib without rheumatic mitral stenosis, mechanical or bioprosthetic heart valve, or mitral valve repair2
Requirements1 - NOTE: Apixaban accumulates in hepatic and/or renal dysfunction
 Stable creatinine clearance (CrCl) greater than 25 mL/min
 Stable liver function with normal indices, LFTs within normal limits
Contraindications1
 Prosthetic heart valves, with/without atrial fibrillation: No data that apixaban provides adequate anticoagulation
Use is NOT recommended.
 Apixaban, like other anticoagulants, is contraindicated in patients at high risk for bleeding.
 Pregnant/Breast feeding: Safety & dosing has not been studied. Use is NOT recommended
 Hepatic disease associated with coagulopathy & clinically relevant bleeding risk. NOTE: Limited information in
moderate-severe hepatic impairment (Child-Pugh class B or C: Score of 7 or greater), particularly those with
associated coagulopathy. Patients with elevated liver enzymes (ALT/AST more than 2 x ULN, or total bilirubin 1.5 or
more x ULN) were excluded from clinical trials.
 Drug Interactions: Concomitant use of strong inducers or inhibitors of both CYP 3A4 and P-glycoprotein - See below.
Potential Limitations
 Drug Interactions: Contraindicated: azole antifungals (excluding fluconazole) and HIV protease inhibitors
(e.g. ritonavir). Avoid: Strong CYP 3A4 and P-gp inducers, such as rifampin, St. John’s Wort and select
anticonvulsants (phenytoin, carbamazepine, phenobarbital)
Rapid decline in anticoagulant effect after a missed dose; adherence is critical
Limited information on patients with extremes of weight (less than 50kg; more than 120kg)
Less than 18 years of age: Safety & dosing has not been studied
Must be able to afford medication; cost varies by drug plan coverage and/or provincial criteria
Limited information on reversal of effect
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May offer an advantage over warfarin if:
 Difficulty stabilizing on warfarin for reasons other than poor medication adherence
 INR monitoring is problematic (e.g. poor venous access, frequent travel, remote location). NOTE: Use of warfarin
with point-of-care (POC) INR testing (e.g. Coaguchek XS™) may be an alternative solution
 Afib: Superior reduction in rate of all cause stroke and systemic embolism, lower rate of major bleeding and clinically
relevant minor bleeding and lower rate of hemorrhagic stroke3
Dosing Recommendations1*
Stroke Prevention in
Non-Valvular Atrial Fibrillation
5mg bid, or 2.5mg bid if TWO or more of:
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Scr 133 µmol/L or greater
80 years or older
60kg or less
DVT/PE
10 mg bid for 7 days, followed by 5 mg bid**
Hip & Knee Replacement
2.5mg bid x 10-14 days (TKR); x 32-38 days (THR)
CrCl Less than 25 mL/min:
No dosing recommendation
CrCl Less than 30 mL/min:
No dosing recommendation
* Limited data suggests may crush & suspend in 60mL D5W PO/NG, but NOT flush with Boost Plus4
** Recommended dose for prevention of recurrent VTE following a least of 6 months of VTE therapy is 2.5 mg bid
Inform Your Patient:
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Atrial Fibrillation: Should decrease risk of stroke by 2/3 compared to no anticoagulation
Carry information indicating they are on an anticoagulant
Can be taken with or without food
Must be taken TWICE daily; adherence is essential to avoid treatment failure
Report signs and symptoms of bleeding, stroke, or DVT/PE
Page 1 of 2
Collaborative Learning on Thrombosis (CLOT) – Canadian Prairie pharmacists with an interest in thromboembolic disorders
This is intended only as a general reference to supplement existing knowledge of healthcare professionals & is not a substitute for sound clinical judgement
CLOT members cannot be held responsible for any harm as a result of application of this information (December 2014)
CLOT
Monitoring Patients on Apixaban
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CrCl should be determined at baseline and at least annually. Monitor more frequently if older than 75y, or with
moderate renal dysfunction (CrCl 30-59mL/min), or when a decline in function suspected.
Monitor for signs and symptoms of bleeding. No routine coagulation testing required. NOTE: INR is not useful. Do
not target INR 2– 3. More specialized testing should only be considered in consultation with a haematologist.
LFTs at baseline (including total bilirubin, albumin, INR) and annually thereafter
Switching Between Agents 1
From warfarin to apixaban:
• Discontinue warfarin and start apixaban once INR 2 or less
From apixaban to warfarin:
• Discontinue apixaban once INR 2 or greater. NOTE: Apixaban may affect INRs, therefore when starting warfarin,
INRs may be unreliable. Check just prior to next apixaban dose as this should more accurately reflect the
anticoagulant effect of warfarin.
From apixaban to parenteral anticoagulants: (e.g. unfractionated heparin, low molecular weight heparin, fondaparinux)
st
• Discontinue apixaban and give the 1 dose of parenteral anticoagulant at the time the next dose of apixaban is due
From parenteral anticoagulants to apixaban:
• For agents administered intermittently, start apixaban at the time the next scheduled dose of the parenteral
anticoagulant. NOTE: For prophylactic dosing of parenteral anticoagulants, apixaban can be started 6 or more hours
after the last dose
• For agents administered by continuous infusion, stop the infusion and start apixaban at the same time
Management of Bleeding Episodes with Apixaban
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Vitamin K and/or protamine will not reverse effects
In the event of major hemorrhagic complications, discontinue apixaban and refer patient for urgent assessment and
to locally developed management strategies
Limited evidence demonstrates prothrombin complex concentrates (e.g. Octaplex®/Beriplex®) are able to reverse
the anticoagulant effect5, but the effect of these agents on bleeding has not been studied.
Anticoagulation Around Invasive Procedures 6,7 (e.g. surgery, major dental procedures)
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As with warfarin, it may not always be necessary to withhold apixaban for minor procedures
Management plans should be made in consultation with the provider performing the procedure
Renal and hepatic function significantly impacts clearance of apixaban. If the recommendations below cannot be
met, consultation with an expert in anticoagulation management is encouraged.
• Due to the onset/offset time of apixiban, peri-procedural use of LMWH not required
Pre-Procedure:
Renal function
(CrCl mL/min)
More than 50
30 - 50
Stop apixaban if required before procedure as follows: (No Doses Morning of Procedure)
Standard Bleeding Risk
Higher Bleeding Risk*
Last dose 2 days prior (Skip 2 doses)
Last dose 3 days prior (Skip 4 doses)
Last dose 3 days prior (Skip 4 doses)
Last dose 4 days prior (Skip 6 doses)
* Consider consultation with anaesthesia, or other specialist in very high risk patients
Post Procedure: Resumption should not be initiated until adequate hemostasis has been achieved or clinical situation
allows (usually 1 -2 days). Full therapeutic effect achieved approximately 2 hours after ingestion.
References:
1. Eliquis Product Monograph (Pfizer Canada Inc. Bristol-Myers Squibb Canada), November 4, 2014.
2. Verma A et al. Can J Cardiology 2014;30:1114-1130.
3. Granger et al. NEJM 2011; 365 (11):981-92.
4. Song Y, Wang X, Perlstein I et al. Clinical Pharmacology and Therapeutics 2013 93 SUPPL. 1(S120-S121). (Abstract)
5. Erenberg ES, et al. Circulation 2011; 124(14):1573-9.
6. Spyropolous A & Douketis JD, Blood 2012; 120 (15):2954-62.
7. Douketis JD; Curr Pharm Des 2010;16(31):3436-3441.
Page 2 of 2 Collaborative Learning on Thrombosis (CLOT) – Canadian Prairie pharmacists with an interest in thromboembolic disorders
This is intended only as a general reference to supplement existing knowledge of healthcare professionals & is not a substitute for sound clinical judgement
CLOT members cannot be held responsible for any harm as a result of application of this information (December 2014)

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