IMPORTANT SAFETY INFORMATION
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.
• 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. An epidural catheter
should not be removed earlier than 18 hours after the
last administration of XARELTO®. The next XARELTO®
dose is not to be administered earlier than 6 hours after
the removal of the catheter. If traumatic puncture occurs,
the administration of XARELTO® is to be delayed for
24 hours. Should the physician decide to administer
anticoagulation in the context of epidural or spinal
anesthesia/analgesia or lumbar puncture, monitor
frequently to detect any signs or symptoms of neurological
impairment, such as midline back pain, sensory and motor
deficits (numbness, tingling, or weakness in lower limbs),
or bowel and/or bladder dysfunction. Instruct patients to
immediately report if they experience any of the above
signs or symptoms. If signs or symptoms of spinal hematoma
are suspected, initiate urgent diagnosis and treatment
including consideration for spinal cord decompression
even though such treatment may not prevent or reverse
neurological sequelae.
Use in Patients With Renal Impairment:
• Nonvalvular Atrial Fibrillation: Avoid the use of XARELTO®
in patients with creatinine clearance (CrCl) <15 mL/min, since
drug exposure is increased. Discontinue XARELTO® in patients
who develop acute renal failure while on XARELTO®.
• Treatment of Deep Vein Thrombosis (DVT), Pulmonary
Embolism (PE), and Reduction in the Risk of Recurrence
of DVT and of PE: Avoid the use of XARELTO® in patients
with CrCl <30 mL/min due to an expected increase in
rivaroxaban exposure and pharmacodynamic effects in
this patient population.
• Prophylaxis of Deep Vein Thrombosis Following Hip or
Knee Replacement Surgery: Avoid the use of XARELTO®
in patients with CrCl <30 mL/min due to an expected increase
in rivaroxaban exposure and pharmacodynamic effects in
this patient population. Observe closely and promptly
evaluate any signs or symptoms of blood loss in patients
with CrCl 30 to 50 mL/mi n. Patients who develop acute renal
failure while on XARELTO® should discontinue the treatment.
Use in Patients With Hepatic Impairment: No clinical data
are available for patients with severe hepatic impairment.
Avoid use of XARELTO® in patients with moderate
(Child-Pugh B) and severe (Child-Pugh C) hepatic impairment
or with any hepatic disease associated with coagulopathy,
since drug exposure and bleeding risk may be increased.
Use With P-gp and Strong CYP3A4 Inhibitors or Inducers:
Avoid concomitant use of XARELTO® with combined
P-gp and strong CYP3A4 inhibitors (eg, ketoconazole,
itraconazole, lopinavir/ritonavir, ritonavir, indinavir, and
conivaptan). Avoid concomitant use of XARELTO® with
drugs that are P-gp and strong CYP3A4 inducers (eg,
carbamazepine, phenytoin, rifampin, St. John’s wort).
Risk of Pregnancy-Related Hemorrhage: In pregnant
women, XARELTO® should be used only if the potential
benefit justifies the potential risk to the mother and
fetus. XARELTO® dosing in pregnancy has not been
studied. The anticoagulant effect of XARELTO® cannot
be monitored with standard laboratory testing and is
not readily reversed. Promptly evaluate any signs or
symptoms suggesting blood loss (eg, a drop in hemoglobin
and/or hematocrit, hypotension, or fetal distress).