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Patients with prosthetic heart valves: Rivaroxaban (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 (see Pharmacology: Pharmacodynamics under Actions).
The safety and efficacy of Rivaroxaban (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.
Concomitant medication: Rivaroxaban (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-antimycotic fluconazole, a moderate CYP 3A4 inhibitor, has however less effect on rivaroxaban exposure and can be co-administered (see Interactions).
Renal Impairment: Rivaroxaban (Xarelto) is to be used with caution in patients with moderate renal impairment (CrC: <50-30 mL/min) receiving co-medications leading to increased rivaroxaban plasma concentrations (see Interactions).
In patients with severe renal impairment (CrC: <30 mL/min), rivaroxaban plasma levels may be significantly elevated (1.6-fold on average) which may lead to an increased bleeding risk. Due to the underlying disease these patients are at an increased risk of both bleeding and thrombosis.
Due to limited clinical data Rivaroxaban (Xarelto) should be used with caution in patients with CrCl <30-15 mL/min (see Pharmacology: Pharmacokinetics under Actions).
No clinical data are available for patients with severe renal impairment (CrCl <15 mL/min). Therefore, use of Rivaroxaban (Xarelto) is not recommended in these patients (see Pharmacology and Pharmacokinetics under Actions and 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).
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.
2.5 mg: This may be done by regular physical examination of the patients, close observation of the surgical wound drainage and periodic measurements of hemoglobin.
10 mg: In patients receiving Rivaroxaban (Xarelto) for the prevention of venous thromboembolism (VTE) after elective hip or knee replacement surgery, this may be done by regular physical examination of the patients, close observation of the surgical wound drainage and periodic measurements of hemoglobin.
In ACS patients, efficacy and safety of Rivaroxaban (Xarelto) 2.5 mg twice daily have been investigated in combination with the antiplatelet agents ASA alone or ASA plus clopidogrel/ticlopidine. Treatment in combination with other antiplatelet agents, e.g. prasugrel or ticagrelor, has not been studied and therefore, is not recommended.
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 2.5 mg twice daily with ASA alone or with ASA plus clopidogrel or ticlopidine in these situations.
To reduce the potential risk of bleeding associated with the concurrent use of rivaroxaban and neuraxial (epidural/spinal) anesthesia or spinal puncture, consider the pharmacokinetic profile of rivaroxaban. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is estimated to be low. However, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known.
The concomitant use of platelet aggregation inhibitors should be considered and such medication discontinued as appropriate.
10 mg: An epidural catheter should not be withdrawn earlier than 18 hours after the last administration of Rivaroxaban (Xarelto).
15 and 20 mg: 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 Rivaroxaban (Xarelto) (see Pharmacology: Pharmacokinetics under Actions).
Rivaroxaban (Xarelto) should be administered at earliest 6 hours after the removal of the catheter.
If traumatic puncture occurs, the administration of Rivaroxaban (Xarelto) should be delayed for 24 hours.
Patients with high risk triple positive antiphospholipid syndrome: Rivaroxaban (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) (see Pharmacology: Pharmacodynamics under Actions).
Bleeding risk: Rivaroxaban (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.
Care should be taken if patients are treated concomitantly with drugs affecting hemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, or other antithrombotics, or selective serotonin reuptake inhibitors (SSRI), and serotonin norepinephrine reuptake inhibitors (SNRIs), (see Interactions).
Patients on treatment with Rivaroxaban (Xarelto) and ASA or with Rivaroxaban (Xarelto) and ASA plus clopidogrel/ticlopidine should only receive chronic concomitant treatment with NSAIDS if the benefit outweighs the bleeding risk.
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, Rivaroxaban (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.
If a patient concomitantly receiving platelet aggregation inhibitors is to undergo elective surgery and anti-platelet effect is not desired, platelet aggregation inhibitors should be discontinued as directed by the manufacturer's prescribing information.
Rivaroxaban (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 (see Pharmacology: Pharmacokinetics under Actions).
Women of childbearing potential: Rivaroxaban (Xarelto) should be used in women of childbearing potential only with effective contraception.
QTc prolongation: No QTc prolonging effect was observed with Rivaroxaban (Xarelto) (see Pharmacology: Pharmacokinetics under Actions).
Information about excipients: Since this medicinal product contains lactose, patients with rare hereditary problems of lactose or galactose intolerance (e.g., the Lapp lactase deficiency or glucose-galactose malabsorption) should not take Rivaroxaban (Xarelto) (see Description).
2.5 mg: ACS, CAD or PAD: Patients with prior stroke and/or TIA: ACS: Rivaroxaban (Xarelto) 2.5 mg twice daily should be avoided for the treatment of ACS in patients with a prior stroke or TIA. Few ACS patients with a prior stroke or TIA have been studied, but the limited efficacy data available indicates that these patients may not benefit from treatment.
CAD or PAD: Patients with haemorrhagic or lacunar stroke: CAD or PAD patients with previous haemorrhagic or lacunar stroke were not studied. Treatment with Rivaroxaban (Xarelto) 2.5 mg twice daily in combination with ASA should be avoided in these patients.
Patients with ischemic, non-lacunar stroke: CAD or PAD patients who have experienced an ischemic, non-lacunar stroke within the previous month were not studied. Treatment with Rivaroxaban (Xarelto) 2.5 mg twice daily in combination with ASA should be avoided in the first month after stroke (see Pharmacology: Pharmacokinetics under Actions).
10, 15 and 20 mg: Treatment and prevention of recurrent DVT and PE: Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Rivaroxaban (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 Rivaroxaban (Xarelto) have not been established in these clinical situations.
10 mg: Hip fracture surgery: Rivaroxaban (Xarelto) has not been studied in interventional clinical trials in patients undergoing hip fracture surgery. Limited clinical data from a non-interventional study are available for patients undergoing fracture related surgery of the lower limbs such as hip fracture surgery (see Pharmacology: Pharmacodynamics under Actions).
15 and 20 mg: 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 Pharmacology: Pharmacodynamics under Actions and Dosage & Administration).
