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IIMPORTANT
MPORTANT SSAFETY
AFETY IINFORMATION
NFORMATION ((cont’d)
cont’d)
WARNINGS AND PRECAUTIONS (cont’d)
•
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/min. 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).
Patients With Prosthetic Heart Valves: The safety
and efficacy of XARELTO® have not been studied in
patients with prosthetic heart valves. Therefore, use
of XARELTO® is not recommended in these patients.
Acute PE in Hemodynamically Unstable Patients/
Patients Who Require Thrombolysis or Pulmonary
Embolectomy: Initiation of XARELTO® is not
recommended acutely as an alternative to
unfractionated heparin in patients with pulmonary
embolism who present with hemodynamic instability
or who may receive thrombolysis or pulmonary
embolectomy.
DRUG INTERACTIONS
Avoid concomitant use of XARELTO® with other
anticoagulants due to increased bleeding risk,
unless benefit outweighs risk. Promptly evaluate
any signs or symptoms of blood loss if patients are
treated concomitantly with aspirin, other platelet
aggregation inhibitors, or NSAIDs.
XARELTO® should not be used in patients with CrCl
15 to <80 mL/min who are receiving concomitant
combined P-gp and moderate CYP3A4 inhibitors (eg,
diltiazem, verapamil, dronedarone, and erythromycin)
unless the potential benefit justifies the potential risk.
USE IN SPECIFIC POPULATIONS
Pregnancy Category C: XARELTO® should be used
during pregnancy only if the potential benefit
justifies the potential risk to mother and fetus.
There are no adequate or well-controlled studies
of XARELTO® in pregnant women, and dosing for
pregnant women has not been established. Use
XARELTO® with caution in pregnant patients because
of the potential for pregnancy-related hemorrhage
and/or emergent delivery with an anticoagulant that
is not readily reversible. The anticoagulant effect
of XARELTO® cannot be reliably monitored with
standard laboratory testing.
Labor and Delivery: Safety and effectiveness of
XARELTO® during labor and delivery have not been
studied in clinical trials.
Based on the following registries, claims databases, and studies: Optum Labs=16,253; IMS Health LifeLink=1,649; Truven Health=5,563; Danish registry=1,303; XAMOS=8,778;
Symphony=3,654; ORTHO-TEP=1,043; Japanese registry=1,035; Dresden NOAC=1,776; XALIA=2,505; DOD database=27,467; XANTUS=6,784.
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