Apixiban Use Guidelines

Indications:

1. Reduction of stroke and systemic embolism in non-valvular atrial fibrillation (AF)
2. Venous thromboembolism (VTE) prophylaxis in patients undergoing knee or hip replacement surgery
3. VTE treatment

Contraindications:

1. Creatinine clearance (CrCl) less than 15ml/min or on dialysis
2. Severe (Child-Pugh C) hepatic impairment
3. Prosthetic mechanical heart valve
4. Pulmonary embolism (PE) complicated by hemodynamic instability or requiring thrombolysis
5. Use of strong dual inducers of P-gp and cytochrome P (CYP) 3A4 (see section III for agents)
6. Use of strong dual inhibitors of P-gp and CYP3A4, dependent upon dose and indication (see sections III and IV)
7. Pediatrics (less than 18 years of age) due to the lack of data to guide safe use
8. Active bleeding
9. Pregnancy or nursing
10. Use of an epidural catheter

1. Dosing differs based upon indication for use.
2. All doses are administered orally every 12 hours.
3. Avoid with strong dual P-gp/CYP3A4 inducers (see III above for agents).

Note: strong dual inhibitors of P-gp/CYP3A4 include ketoconazole, itraconazole, ritonavir and clarithromycin as noted in section III.

*Initial dose should be given 12-24 hours after surgery once hemostasis has been established.

† Dose reduction criteria include: 1) Age greater than or equal to 80 years; 2) Body weight less than or equal to 60 kg; and, 3) SCr greater than or equal to 1.5 mg/dL.

1. If a dose of apixaban is missed and the next dose is due within 6 hours, skip the missed dose and resume the previous dosing schedule. The dose should not be doubled to make up for a missed dose.
2. Apixaban can be crushed and administered through a feeding tube.

Baseline monitoring

1. aPTT, INR/PT, platelet count, hemoglobin/hematocrit, and serum creatinine

On-going monitoring

1. Patients in an intensive care unit will have serum creatinine monitored at least every 3 days. All other patients will have serum creatinine monitored at least once per week. Hemoglobin/hematocrit will be monitored at least weekly while hospitalized.
2. On-going monitoring of anticoagulant assays is not routinely recommended.

1. Black Box Warning: Discontinuing apixaban places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of apixaban in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.
2. There is a lack of data regarding these conversion strategies but they represent reasonable strategies when conversion is necessary.
3. Converting from warfarin to apixaban
   • Discontinue warfarin and begin apixaban when the INR is below 2.0.
4. Converting from apixaban to warfarin
   • Apixaban affects INR. INR measurements during coadministration with warfarin may not be useful for determining appropriate dose of warfarin.
   • If continuous anticoagulation is necessary, discontinue apixaban and begin warfarin with a concomitant parenteral anticoagulant when the next dose of apixaban would have been due, discontinuing the parenteral anticoagulant when INR reaches goal range.
5. Converting from another anticoagulant other than warfarin to apixaban

   Alternate Anticoagulant	Time after last dose of alternate anticoagulant before start of apixaban
   Unfractionated heparin or parenteral direct thrombin inhibitor intravenous continuous infusion	Start apixaban immediately upon discontinuation of continuous infusion
   Subcutaneous LMWH or fondaparinux; oral dabigatran, rivaroxaban	Start apixaban 0-2 hours before the next dose of alternate anticoagulant was to be administered

6. Converting from apixaban to another anticoagulant other than warfarin
   • Discontinue apixaban and begin the alternate anticoagulant at the time the next dose of apixaban would have been given

1. Pre-operative/Pre-procedural management
   • Low thrombotic risk★ patients

     Apixaban pre-procedural management in Low thrombotic risk★ patients
     CrCl (mL/min)	Time after last dose of apixaban before procedure
     	Standard risk of bleeding	High risk of bleeding†
     Greater than or equal to 50	2 days	4 days
     Less than 50	4 days	5 days

   • Intermediate -high thrombotic risk# patients

     Apixaban pre-procedural management in Intermediate-high thrombotic risk# patients
     CrCl (mL/min)	Time after last dose of apixaban before procedure
     	Standard risk of bleeding	High risk of bleeding†
     Greater than or equal to 50	1 day	2 days
     Less than 50	2 days	3 days

     ★#Patient criteria as outlined in UMHS Perioperative and Periprocedural Warfarin Guidelines for Adult and Pediatric Patients

     † Types of surgery associated with a high risk of bleeding (or in major surgery where complete hemostasis may be required) may include but are not limited to cardiac surgery, neurosurgery, or others determined by the proceduralist or surgeon. Other procedures such as spinal anesthesia may also require complete hemostatic function. Other important determinants of bleeding risk may include advancing age, co-morbidities (e.g. renal or liver disease) and concomitant use of antiplatelet therapy.

2. Bridging with a parenteral anticoagulant prior to a procedure/operation is not necessary. However, prescribers may choose to use a parenteral anticoagulant instead of apixaban prior to surgery.
3. Post-operative/Post-procedural management
   • Resuming treatment dose apixaban is subject to surgeon or proceduralist approval based upon achievement of adequate hemostasis.
4. Central Neuraxial Blockade
   • Use of apixaban during the use of central neuraxial blockade is contraindicated.
   • Apixaban should be discontinued at least 24 hours before epidural catheter placement.
   • Apixaban may be restarted 6 hours after epidural catheter removal

1. There is no antidote available in the United States for apixaban