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IMPORTANT SAFETY INFORMATION
WARNING: (A) PREMATURE DISCONTINUATION OF
XARELTO® INCREASES THE RISK OF THROMBOTIC EVENTS,
(B) SPINAL/EPIDURAL HEMATOMA
A. PREMATURE DISCONTINUATION OF XARELTO®
INCREASES THE RISK OF THROMBOTIC EVENTS
Premature discontinuation of any oral anticoagulant,
including XARELTO®, increases the risk of thrombotic
events. If anticoagulation with XARELTO® is discontinued
for a reason other than pathological bleeding or
completion of a course of therapy, consider coverage
with another anticoagulant.
B. SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas have occurred in patients
treated with XARELTO® who are receiving neuraxial
anesthesia or undergoing spinal puncture. These
hematomas may result in long-term or permanent
paralysis. Consider these risks when scheduling patients
for spinal procedures. Factors that can increase the risk
CONTRAINDICATIONS
Active pathological bleeding
Severe hypersensitivity reaction to XARELTO®
(eg, anaphylactic reactions)
WARNINGS AND PRECAUTIONS
Increased Risk of Thrombotic Events After Premature
Discontinuation: Premature discontinuation of any
oral anticoagulant, including XARELTO®, in the absence
of adequate alternative anticoagulation increases the
risk of thrombotic events. An increased rate of stroke
was observed during the transition from XARELTO® to
warfarin in clinical trials in atrial fibrillation patients.
If XARELTO® is discontinued for a reason other than
pathological bleeding or completion of a course of
therapy, consider coverage with another anticoagulant.
Risk of Bleeding: XARELTO® increases the risk of
bleeding and can cause serious or fatal bleeding.
Promptly evaluate any signs or symptoms of blood
loss and consider the need for blood replacement.
Discontinue XARELTO® in patients with active
pathological hemorrhage.
of developing epidural or spinal hematomas in these
patients include:
Use of indwelling epidural catheters
Concomitant use of other drugs that affect hemostasis,
such as non-steroidal anti-inflammatory drugs
(NSAIDs), platelet inhibitors, other anticoagulants,
see Drug Interactions
A history of traumatic or repeated epidural or spinal
punctures
A history of spinal deformity or spinal surgery
Optimal timing between the administration of
XARELTO® and neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of
neurological impairment. If neurological compromise is
noted, urgent treatment is necessary.
Consider the benefits and risks before neuraxial
intervention in patients anticoagulated or to be
anticoagulated for thromboprophylaxis.
A specific antidote for rivaroxaban is not available.
Because of high plasma protein binding, rivaroxaban is
not expected to be dialyzable.
• Concomitant use of other drugs that impair hemostasis
increases the risk of bleeding. These include aspirin,
P2Y12 platelet inhibitors, other antithrombotic agents,
fibrinolytic therapy, and NSAIDs.
Spinal/Epidural Anesthesia or Puncture: When
neuraxial anesthesia (spinal/epidural anesthesia) or
spinal puncture is employed, patients treated with
anticoagulant agents for prevention of thromboembolic
complications are at risk of developing an epidural
or spinal hematoma, which can result in long-term
or permanent paralysis. To reduce the potential risk
of bleeding associated with the concurrent use of
rivaroxaban and epidural or spinal anesthesia/analgesia
or spinal puncture, consider the pharmacokinetic
profile of rivaroxaban. Placement or removal of an
epidural catheter or lumbar puncture is best performed
when the anticoagulant effect of rivaroxaban is low;
however, the exact timing to reach a sufficiently low
anticoagulant effect in each patient is not known.
•
References: 1. Beyer-Westendorf J, Förster K, Pannach S, et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood.
2014;124(6):955-962. doi: 10.1182/blood-2014-03-563577. 2. Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of thromboprophylaxis with low-molecular-weight
heparin or rivaroxaban in hip and knee replacement surgery. Findings from the ORTHO-TEP registry. Thromb Haemost. 2013;109(1):154-163. doi: 10.1160/TH12-07-0510. 3. Ogawa S, Ikeda T,
Kitazono T, et al; on behalf of the Rivaroxaban Postmarketing Surveillance Registry Investigators. Present profiles of novel anticoagulant use in Japanese patients with atrial fibrillation:
insights from the rivaroxaban postmarketing surveillance registry. J Stroke Cerebrovasc Dis. 2014;23(10):2520-2526. doi: 10.1016/j.jstrokecerebrovasdis.2014.03.006. 4. Laliberté F, Cloutier M,
Nelson WW, et al. Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin. 2014;30(7):1317-1325.
5. Turpie AGG, Haas S, Kreutz R, et al. A non-interventional comparison of rivaroxaban with standard of care for thromboprophylaxis after major orthopaedic surgery in 17,701 patients with
propensity score adjustment. Thromb Haemost. 2014; 111(1):94-102. doi: 10.1160/TH13-08-0666. 6. Abraham NS, Singh S, Alexander CG, et al. Comparative risk of gastrointestinal bleeding
with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015;350:h1857. doi: http://dx.doi.org/10.1136/bmj.h1857. 7. Chang H-Y, Zhou M, Tang W, Alexander GC,
Singh S. Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study. BMJ. 2015;350:h1585. doi: http://dx.doi.org/10.1136/bmj.h1585.
8. Lauffenburger JC, Farley JF, Gehi AK, Rhoney DH, Brookhart MA, Fang G. Factors driving anticoagulant selection in patients with atrial fibrillation in the United States. Am J Cardiol.
2015;115(8):1095-1101. http://dx.doi.org/10.1016/j.amjcard.2015.01.539. 9. Olesen JB, Sørensen R, Hansen ML, et al. Non-vitamin K antagonist oral anticoagulation agents in anticoagulant
naïve atrial fibrillation patients: Danish nationwide descriptive data 2011–2013. Europace. 2015;17(2):187-193. doi: 10.1093/europace/euu225. 10. Camm AJ, Amarenco P, Haas S, et al.
XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2015;1-9. doi:10.1093/eurheartj/ehv466.
11. Tamayo S, Peacock WF, Patel M, et al. Characterizing major bleeding in patients with non-valvular atrial fibrillation: a pharmacovigilance study of 27,467 patients taking rivaroxaban.
Clin Cardiol. 2015;38(2):63-68. doi: 10.1002/clc.22373. 12. Patel MR, Mahaffey KW, Garg J, et al; and the ROCKET AF Steering Committee, for the ROCKET AF Investigators. Rivaroxaban
versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891.