Rivaroxaban Use Guidelines

Inclusion:

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

Exclusion:

1. Creatinine clearance (CrCl), differing based upon indication (see Section III. Dosing)
   • VTE prophylaxis and treatment – less than 30 mL/min
   • AF – less than 15ml/min
2. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment or with hepatic disease associated with coagulopathy
3. Prosthetic mechanical heart valve
4. Pediatrics (less than 18 years of age) due to the lack of data to guide safe use
5. Active bleeding
6. Pregnancy or nursing
7. Use of an epidural catheter

1. Dosing differs based upon indication for use and renal function, expressed as ml/min as calculated via the Cockroft-Gault equation.
2. All doses are administered orally.

*Initial dose should be given 6-10 hours after surgery once hemostasis is established

1. Rivaroxaban can be crushed and administered in a feeding tube, but gastric placement is required to assure adequate drug absorption
2. In patients receiving rivaroxaban for reduction of stroke and systemic embolism in AF, routine administration time will default to 17:00 with the evening meal. This is in order to ensure complete absorption of the drug for this indication only.
3. In patients receiving rivaroxaban for VTE treatment, routine administration time will default to 06:00 and 18:00 for twice daily dosing and 17:00 for once daily dosing so doses will be given with meals.
4. In patients receiving rivaroxaban for VTE prophylaxis, the drug will be administered q24h with no default time, in order to allow for first doses to be timed according to surgical time and achievement of hemostasis. There is no concern for absorption with the 10mg dose used for this indication thus it may be given at any time of the day without regard for food.

Baseline monitoring

1. aPTT, INR/PT, platelet count, and 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 rivaroxaban in patients being treated for atrial fibrillation places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of rivaroxaban in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with rivaroxaban 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 rivaroxaban
   • Discontinue warfarin and begin rivaroxaban when the INR is equal to or below 2.0.
4. Converting from rivaroxaban to warfarin
   • When converting from rivaroxaban to warfarin the INR is unlikely to be useful for several days.
   • Discontinue rivaroxaban and begin warfarin bridged with a concomitant parenteral anticoagulant when the next dose of rivaroxaban would have been due if continuous therapeutic anticoagulation is required.
5. Converting from another anticoagulant other than warfarin to rivaroxaban

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

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

1. For patients receiving rivaroxaban for VTE prophylaxis (10mg), rivaroxaban should be stopped at least 24 hours before the procedure.
2. For patients receiving treatment doses (15-20mg) of rivaroxaban:
   • Low thrombotic risk★ patients

     Rivaroxaban pre-procedural management in Low thrombotic risk★ patients
     CrCl (mL/min)	Time after last dose of rivaroxaban 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

     Rivaroxaban pre-procedural management in Intermediate-high thrombotic risk# patients
     CrCl (mL/min)	Time after last dose of rivaroxaban 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.

3. Bridging with a parenteral anticoagulant prior to a procedure/operation is not necessary. However, physicians may choose to use a parenteral anticoagulant instead of rivaroxaban prior to surgery.
4. Post-operative/Post-procedural management
   • Resuming treatment dose rivaroxaban is subject to surgeon or interventionalist approval based upon achievement of adequate hemostasis.
   • Prophylactic rivaroxaban after hip/knee replacement should be initiated 6 to 10 hours after surgery once hemostasis is achieved
5. Central Neuraxial Blockade
   • Use of rivaroxaban during the use of central neuraxial blockade is contraindicated.
   • Rivaroxaban should be discontinued at least 24 hours before epidural catheter placement.
   • Rivaroxaban may be restarted 6 hours after epidural catheter removal

     (See Antithrombotic/Antiplatelet Agents & Central Neuraxial Blockade Guidelines for Adult and Pediatric Patients)

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