Description
What is Xarelto (Rivaroxaban)?
Xarelto is a factor Xa inhibitor used to:
- Decrease the risk of systemic embolism in nonvalvular atrial fibrillation and stroke
- Treat pulmonary embolism (PE)
- Treat deep vein thrombosis (DVT)
- Decrease the risk of PE or DVT
- Provide prophylaxis for venous thromboembolism (VTE) in medical patients that are acutely ill
- Provide prophylaxis for DVT, which can cause PE in those undergoing hip or knee replacement surgery
- Decrease the chance of a major cardiovascular event in those with coronary artery disease (CAD)
- Decrease the chance of peripheral artery disease (PAD), including those with recent lower extremity revascularization caused by symptomatic PAD
How does Xarelto work?
Xarelto selectively inhibits factor Xa (FXa). It blocks prothrombinase activity and free FXa and does not require a cofactor. It does not have direct effects on platelet aggregation. However, it does indirectly block platelet aggregation caused by thrombin. By blocking FXa, Xarelto reduces thrombin production.
Side Effects
Common side effects of Xarelto include:
- Bleeding
- Abdominal pain
- Back pain
- Itching
- Dizziness
- Muscle spasms
- Anxiety and depression
- Insomnia
- Fatigue
Warnings & Precautions
Elevated Risk of Thrombotic Events After Premature Discontinuation
Early discontinuation of Xarelto without alternative anticoagulation elevates one’s risk of a thrombotic event. In clinical trials, patients transitioning from Xarelto to warfarin demonstrated a higher rate of stroke. Adequate anticoagulant coverage should be initiated when discontinuing Xarelto unless the patient is stopping due to bleeding or completion of therapy.
Bleeding Risk
Xarelto elevates an individual’s risk of bleeding and can cause fatal or severe bleeding. In high-risk patients, providers should weigh the risk of bleeding against the risk of thrombotic events.
In patients that experience bleeding, providers should assess for blood loss and consider blood replacement. Xarelto should be stopped in individuals that have active pathological hemorrhage. The terminal elimination half-life of Xarelto is between five and nine hours in healthy individuals.
Use of other drugs that alter hemostasis with Xarelto can increase a patient’s risk of bleeding. These drugs include P2Y12 platelet inhibitors, aspirin, dual antiplatelet therapy, non-steroidal anti-inflammatory drugs (NSAIDs), fibrinolytic drugs, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and other antithrombotic agents.
If Xarelto is used with drugs that are both CYP3A4 and P-gp inhibitors, Xarelto concentrations can be increased and pose a higher bleeding risk.
Spinal/Epidural Anesthesia or Puncture
Patients on anticoagulant prophylaxis undergoing spinal or epidural anesthesia are at increased risk of spinal or epidural hematoma. This condition can cause permanent paralysis. To reduce this risk, the removal or placement of the lumbar puncture or epidural catheter should be done when Xarelto’s anticoagulant effects are low. It is unknown exactly when these effects are lowest.
To calculate this, the intrathecal or epidural catheter should not be taken out prior to the elapse of two half-lives post-Xarelto administration. Xarelto should not be taken earlier than six hours after catheter removal. In the case of a traumatic puncture, Xarelto should not be taken for 24 hours.
Providers that decide to give anticoagulation in this instance should frequently monitor neurological impairment symptoms. If the patient develops signs of spinal hematoma, providers should start urgent treatment.
Individuals with Renal Impairment
Dose considerations should be made in the following types of patients:
Those with nonvalvular atrial fibrillation. Those that experience acute renal failure with Xarelto should have the dose of Xarelto reduced or stop Xarelto.
Those with DVT and PE. Xarelto exposure can be increased with renal impairment. Therefore, use caution in patients with renal dysfunction. Avoid Xarelto in those with a CrCl <15 mL/min. Stop Xarelto if a patient develops acute renal failure.
Those on DVT prophylaxis after knee or hip surgery. Xarelto exposure can be increased with renal impairment. Therefore, use caution in patients with renal dysfunction. Avoid Xarelto in those with a CrCl <15 mL/min. Stop Xarelto if a patient develops acute renal failure.
Those on VTE prophylaxis that are acutely ill and at risk for thromboembolic events but are not at high risk for bleeding. Xarelto exposure can be increased with renal impairment. Therefore, use caution in patients with renal dysfunction. Avoid Xarelto in those with a CrCl <15 mL/min. Stop Xarelto if a patient develops acute renal failure.
Individuals with Hepatic Impairment
There is no data on the use of Xarelto in those with serious hepatic impairment. Therefore, Xarelto should be avoided in those with moderate and severe hepatic impairment. Additionally, it should be avoided in hepatic disease that has coagulopathy. Xarelto can increase bleeding risk in these patients.
Administration with Strong CYP3A and P-gp Inducers and Inhibitors
Do not use Xarelto with medications that are both strong CYP3A and P-gp inhibitors. Do not use Xarelto with medications that are both strong CYP3A and P-gp inducers.
Pregnancy-Related Hemorrhage
Xarelto has not been studied in pregnant women, and therefore it should only be used in pregnant women if the benefits outweigh the risks.
Individuals with Prosthetic Heart Valves
In the GALILEO trial, patients on Xarelto had a higher incidence of bleeding and death than those on antiplatelet therapy. Xarelto’s safety and efficacy in those with prosthetic heart valves and other valve procedures is unknown. Therefore, Xarelto is not recommended in these patients.
Thrombosis Risk in Individuals with Triple Positive Antiphospholipid Syndrome (APS)
Direct-acting oral anticoagulants (DOACs) like Xarelto should not be used in individuals with APS. APS patients treated with DOACs have demonstrated increased incidence of thrombotic events compared with warfarin.
Drug Interactions
Inhibitors of CYP450 3A and Drug Transport Systems
Avoid taking Xarelto with drugs that are both a strong P-gp and CYP3A inhibitor. Xarelto should not be taken with drugs that are moderate P-gp and CYP3A inhibitors in the presence of renal impairment.
Inducers of CYP450 3A and Drug Transport System
Avoid taking Xarelto with drugs that are both a strong P-gp and CYP3A inducers.
NSAIDs, Aspirin, and Anticoagulants
Taking Xarelto with these agents can elevate one’s risk of bleeding. Xarelto should be avoided if taking other anticoagulants because of the high risk of bleed.
