Xarelto Special Precautions

Patients with prosthetic heart valves: Xarelto is not recommended for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement (TAVR) based on data from a randomized controlled clinical study comparing a Xarelto-regimen to an antiplatelet regimen.
The safety and efficacy of Xarelto have not been studied in patients with other prosthetic heart valves or other valve procedures; therefore, there are no data to support that Xarelto provides adequate anticoagulation in those patient populations.
Patients with high risk triple positive antiphospholipid syndrome: Xarelto is not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome and are persistently triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies) as treatment with rivaroxaban is associated with an increased rate of recurrent thrombotic events compared with vitamin K antagonists (VKA).
Concomitant medication: Xarelto is not recommended in patients receiving concomitant systemic treatment with azole-antimycotics (e.g. ketoconazole) or HIV protease inhibitors (e.g. ritonavir). These drugs are strong inhibitors of both CYP 3A4 and P-gp. Therefore, these drugs may increase rivaroxaban plasma concentrations to a clinically relevant degree (2.6-fold on average) which may lead to an increased bleeding risk (see 'Interactions').
The azole anti-mycotic fluconazole, a moderate CYP 3A4 inhibitor, has however less effect on rivaroxaban exposure and can be co-administered (see 'Interactions').
Treatment and prevention of recurrent DVT and PE: Renal impairment: Xarelto is to be used with caution in patients with moderate renal impairment receiving co-medications leading to increased rivaroxaban plasma concentrations (see 'Interactions').
SPAF, treatment and prevention of recurrent DVT and PE: Renal impairment: In patients with severe renal impairment rivaroxaban plasma levels may be significantly elevated (1.6-fold on average) which may lead to an increased bleeding risk.
Due to limited clinical data Xarelto should be used with caution in patients with CrC <30 - 15 mL/min.
No clinical data are available for patients with severe renal impairment. Therefore use of Xarelto is not recommended in these patients (see 'Dosage & Administration').
Patients with severe renal impairment or increased bleeding risk and patients receiving concomitant systemic treatment with azole-antimycotics or HIV protease inhibitors are to be carefully monitored for signs of bleeding complications after initiation of treatment (see 'Interactions').
Bleeding risk: Xarelto like other antithrombotics should be used with caution in patients with an increased bleeding risk such as: congenital or acquired bleeding disorders; uncontrolled severe arterial hypertension; active ulcerative gastrointestinal disease; recent gastrointestinal ulcerations; vascular retinopathy; recent intracranial or intracerebral hemorrhage; intraspinal or intracerebral vascular abnormalities; recent brain, spinal or ophthalmological surgery; bronchiectasis or history of pulmonary bleeding.
Bleeding during antithrombotic treatment may unmask underlying yet unknown malignancy, in particular in the gastrointestinal or genitourinary tract. Patients with malignant disease may simultaneously be at higher risk of bleeding and thrombosis. The individual benefit of antithrombotic treatment should be weighed against risk for bleeding in patients with active cancer dependent on tumor location, antineoplastic therapy and stage of disease.
Care should be taken if patients are treated concomitantly with drugs affecting hemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, other antithrombotics or selective serotonin reuptake inhibitors (SSRI), and serotonin norepinephrine reuptake inhibitors (SNRIs) (see 'Interactions').
For patients at risk of ulcerative gastrointestinal disease an appropriate prophylactic treatment may be considered (see 'Interactions').
Any unexplained fall in hemoglobin or blood pressure should lead to a search for a bleeding site.
Surgery and interventions: If an invasive procedure or surgical intervention is required, Xarelto should be stopped at least 24 hours before the intervention, if possible and based on clinical judgment of the physician.
If the procedure cannot be delayed, the increased risk of bleeding should be assessed against the urgency of the intervention.
Xarelto should be restarted as soon as possible after the invasive procedure or surgical intervention provided the clinical situation allows and adequate hemostasis has been established.
Neuraxial (epidural/spinal) anesthesia: When neuraxial (epidural/spinal) anesthesia or spinal puncture is performed, patients treated with antithrombotics for prevention of thromboembolic complications are at risk for development of an epidural or spinal hematoma which may result in long-term paralysis.
The risk of these events is even further increased by use of indwelling epidural catheters or the concomitant use of drugs affecting hemostasis. The risk may also be increased by traumatic or repeated epidural or spinal puncture.
Patients should be frequently monitored for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological deficits are noted, urgent diagnosis and treatment is necessary.
The physician should consider the potential benefit versus the risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
There is no clinical experience with the use of 15 mg and 20 mg rivaroxaban in these situations.
For the removal of an epidural catheter and based on the general PK characteristics at least 2x half-life should elapse, i.e. at least 18 hour in young patients and 26 hours in elderly patients, after the last administration of Xarelto.
Xarelto should be administered at earliest 6 hours after the removal of the catheter.
If traumatic puncture occurs, the administration of Xarelto should be delayed for 24 hours.
Treatment and prevention of recurrent DVT and PE: Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Xarelto is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and efficacy of Xarelto have not been established in these clinical situations.
SPAF: Patients who undergo PCI with stent placement: Clinical data are available from an interventional study with the primary objective to assess safety in patients with non-valvular atrial fibrillation who undergo PCI with stent placement. Data on efficacy in this population are limited (see 'Dosage & Administration').
Effects on ability to drive or use machines: Syncope and dizziness have been reported and may affect the ability to drive and use machines (see 'Adverse Reactions'). Patients experiencing these adverse reactions should not drive or use machines.
Use in Pregnancy: Women of childbearing potential: Xarelto should be used in women of childbearing potential only with effective contraception.