XARELTO

Generic Name/API: RIVAROXABAN

Manufacturer: Janssen Pharmaceuticals

Dosage Forms & Strength & Pack Size:
Tablet, 10 mg, 15 mg, 20 mg, 30’s

Storage:
Tablets should be kept in a cool, dry place where
the temperature stays below 30°C. Store all
medicines out of reach of children.

  • INDICATION
  • IMPORTANT SAFETY INFORMATION

XARELTO is a factor Xa inhibitor indicated:
to reduce risk of stroke and systemic embolism in nonvalvular atrial fibrillation ( 1.1)
for treatment of deep vein thrombosis (DVT) ( 1.2)
for treatment of pulmonary embolism (PE) ( 1.3)
for reduction in the risk of recurrence of DVT or PE ( 1.4)
for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement
surgery ( 1.5)
for prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients ( 1.6)
to reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD) ( 1.7)
to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD),
including patients after recent lower extremity revascularization due to symptomatic PAD ( 1.8)
for treatment of VTE and reduction in the risk of recurrent VTE in pediatric patients from birth to less
than 18 years ( 1.9)
for thromboprophylaxis in pediatric patients 2 years and older with congenital heart disease after the
Fontan procedure ( 1.10)

WARNINGS AND PRECAUTIONS
1 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 [see Dosage and Administration (2.3, 2.4) and Clinical Studies
(14.1)] .
2 Risk of Bleeding
XARELTO increases the risk of bleeding and can cause serious or fatal bleeding. In
deciding whether to prescribe XARELTO to patients at increased risk of bleeding, the risk
of thrombotic events should be weighed against the risk of 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. The
terminal elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to
45 years.
Concomitant use of other drugs that impair hemostasis increases the risk of bleeding.
These include aspirin, P2Y platelet inhibitors, dual antiplatelet therapy, other
antithrombotic agents, fibrinolytic therapy, non-steroidal anti-inflammatory drugs
(NSAIDs) [see Drug Interactions (7.4)] , selective serotonin reuptake inhibitors, and
serotonin norepinephrine reuptake inhibitors.
Concomitant use of drugs that are known combined P-gp and strong CYP3A inhibitors
increases rivaroxaban exposure and may increase bleeding risk [see Drug Interactions
(7.2)] .
Risk of Hemorrhage in Acutely Ill Medical Patients at High Risk of Bleeding
Acutely ill medical patients with the following conditions are at increased risk of bleeding
with the use of XARELTO for primary VTE prophylaxis: history of bronchiectasis,
pulmonary cavitation, or pulmonary hemorrhage, active cancer (i.e., undergoing acute,
in-hospital cancer treatment), active gastroduodenal ulcer in the three months prior to
treatment, history of bleeding in the three months prior to treatment, or dual antiplatelet
therapy. XARELTO is not for use for primary VTE prophylaxis in these hospitalized,
acutely ill medical patients at high risk of bleeding.
Reversal of Anticoagulant Effect
An agent to reverse the anti-factor Xa activity of rivaroxaban is available. Because of
high plasma protein binding, rivaroxaban is not dialyzable [see Clinical Pharmacology
(12.3)] . Protamine sulfate and vitamin K are not expected to affect the anticoagulant
activity of rivaroxaban. Use of procoagulant reversal agents, such as prothrombin
complex concentrate (PCC), activated prothrombin complex concentrate or
recombinant factor VIIa, may be considered but has not been evaluated in clinical
efficacy and safety studies. Monitoring for the anticoagulation effect of rivaroxaban
using a clotting test (PT, INR or aPTT) or anti-factor Xa (FXa) activity is not
recommended.
3 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 [see Boxed Warning] .
To reduce the potential risk of bleeding associated with the concurrent use of XARELTO
and epidural or spinal anesthesia/analgesia or spinal puncture, consider the
12
pharmacokinetic profile of XARELTO [see Clinical Pharmacology (12.3)] . Placement or
removal of an epidural catheter or lumbar puncture is best performed when the
anticoagulant effect of XARELTO is low; however, the exact timing to reach a sufficiently
low anticoagulant effect in each patient is not known.
An indwelling epidural or intrathecal catheter should not be removed before at least 2
half-lives have elapsed (i.e., 18 hours in young patients aged 20 to 45 years and 26
hours in elderly patients aged 60 to 76 years), after the last administration of XARELTO
[see Clinical Pharmacology (12.3)] . The next XARELTO dose should not be administered
earlier than 6 hours after the removal of the catheter. If traumatic puncture occurs,
delay the administration of XARELTO 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), 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.
4 Use in Patients with Renal Impairment
Nonvalvular Atrial Fibrillation
Periodically assess renal function as clinically indicated (i.e., more frequently in situations
in which renal function may decline) and adjust therapy accordingly [see Dosage and
Administration (2.1)] . Consider dose adjustment or discontinuation of XARELTO in
patients who develop acute renal failure while on XARELTO [see Use in Specific
Populations (8.6)].
Treatment of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reduction in
the Risk of Recurrence of DVT and of PE
In patients with CrCl <30 mL/min, rivaroxaban exposure and pharmacodynamic effects are increased compared to patients with normal renal function. There are limited clinical data in patients with CrCl 15 to <30 mL/min; therefore, observe closely and promptly evaluate any signs or symptoms of blood loss in these patients. There are no clinical data in patients with CrCl <15 mL/min (including patients on dialysis); therefore, avoid the use of XARELTO in these patients. Discontinue XARELTO in patients who develop acute renal failure while on treatment [see Use in Specific Populations (8.6)] . Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery In patients with CrCl <30 mL/min, rivaroxaban exposure and pharmacodynamic effects are increased compared to patients with normal renal function. There are limited clinical data in patients with CrCl 15 to <30 mL/min; therefore, observe closely and promptly evaluate any signs or symptoms of blood loss in these patients. There are no clinical data in patients with CrCl <15 mL/min (including patients on dialysis); therefore, avoid the use of XARELTO in these patients. Discontinue XARELTO in patients who develop acute renal failure while on treatment [see Use in Specific Populations (8.6)]. Prophylaxis of Venous Thromboembolism in Acutely Ill Medical Patients at Risk for Thromboembolic Complications Not at High Risk of Bleeding In patients with CrCl <30 mL/min, rivaroxaban exposure and pharmacodynamic effects are increased compared to patients with normal renal function. There are limited clinical data in patients with CrCl 15 to <30 mL/min; therefore, observe closely and promptly evaluate any signs or symptoms of blood loss in these patients. There are no clinical data in patients with CrCl <15 mL/min (including patients on dialysis); therefore, avoid the use of XARELTO in these patients. Discontinue XARELTO in patients who develop acute renal failure while on treatment [see Use in Specific Populations (8.6)]. Pediatric Patients There are limited clinical data in pediatric patients 1 year or older with moderate or severe renal impairment (eGFR <50 mL/min/1.73 m ); therefore, avoid the use of XARELTO in these patients. There are no clinical data in pediatric patients younger than 1 year with serum creatinine results above 97.5 percentile; therefore, avoid the use of XARELTO in these patients [see Dosage and Administration (2.2) and Use in Specific Populations (8.6)] . 5 Use in Patients with Hepatic Impairment No clinical data are available for adult 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 [see Use in Specific Populations (8.7)] . No clinical data are available in pediatric patients with hepatic impairment. 6 Use with P-gp and Strong CYP3A Inhibitors or Inducers Avoid concomitant use of XARELTO with known combined P-gp and strong CYP3A inhibitors [see Drug Interactions (7.2)] . Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions (7.3)] . 7 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. Promptly evaluate any signs or symptoms suggesting blood loss (e.g., a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress) [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)] . 8 Patients with Prosthetic Heart Valves On the basis of the GALILEO study, use of XARELTO is not recommended in patients who have had transcatheter aortic valve replacement (TAVR) because patients 2 th randomized to XARELTO experienced higher rates of death and bleeding compared to those randomized to an anti-platelet regimen. The safety and efficacy of XARELTO have not been studied in patients with other prosthetic heart valves or other valve procedures. Use of XARELTO is not recommended in patients with prosthetic heart valves. 9 Acute PE in Hemodynamically Unstable Patients or 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. 10 Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome Direct-acting oral anticoagulants (DOACs), including XARELTO, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS). For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

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