WARNINGS AND PRECAUTIONS (cont’d)
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/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/ritonavir, 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 unless the potential benefit
justifies the potential risk.
USE IN SPECIFIC POPULATIONS
T:14 in
B:14.25 in
S:13 in
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 wellcontrolled 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.
Nursing Mothers: It is not known if rivaroxaban is excreted in
human milk.
Pediatric Use: Safety and effectiveness in pediatric patients
have not been established.
Females of Re