Xarelto Special Precautions

Clinical surveillance in line with anticoagulation practice is recommended throughout the treatment period.
Haemorrhagic risk: As with other anticoagulants, patients taking Xarelto are to be carefully observed for signs of bleeding. It is recommended to be used with caution in conditions with increased risk of haemorrhage. Xarelto administration should be discontinued if severe haemorrhage occurs.
In the clinical studies mucosal bleedings (i.e. epistaxis, gingival, gastrointestinal, genito urinary) and anaemia were seen more frequently during long term rivaroxaban treatment compared with VKA treatment. Thus, in addition to adequate clinical surveillance, laboratory testing of haemoglobin/haematocrit could be of value to detect occult bleeding, as judged to be appropriate.
Several sub-groups of patients, as detailed below, are at increased risk of bleeding. These patients are to be carefully monitored for signs and symptoms of bleeding complications and anaemia after initiation of treatment (see Adverse Reactions).
Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site.
Although treatment with rivaroxaban does not require routine monitoring of exposure, rivaroxaban levels measured with a calibrated quantitative anti-factor Xa assay may be useful in exceptional situations where knowledge of rivaroxaban exposure may help to inform clinical decisions, e.g., overdose and emergency surgery (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Renal impairment: In patients with severe renal impairment (creatinine clearance < 30 ml/min) rivaroxaban plasma levels may be significantly increased (1.6 fold on average) which may lead to an increased bleeding risk. Xarelto is to be used with caution in patients with creatinine clearance 15 - 29 ml/min. Use is not recommended in patients with creatinine clearance < 15 ml/min (see Pharmacology: Pharmacokinetics under Actions and Dosage & Administration).
Xarelto should be used with caution in patients with renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations (see Interactions).
Interaction with other medicinal products: The use of Xarelto is not recommended in patients receiving concomitant systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir). These active substances are strong inhibitors of both CYP3A4 and P-gp and therefore 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).
Care is to be taken if patients are treated concomitantly with medicinal products affecting haemostasis such as non-steroidal anti-inflammatory medicinal products (NSAIDs), acetylsalicylic acid and platelet aggregation inhibitors. For patients at risk of ulcerative gastrointestinal disease an appropriate prophylactic treatment may be considered (see Interactions).
Other haemorrhagic risk factors: As with other antithrombotics, rivaroxaban is not recommended in patients with an increased bleeding risk such as: congenital or acquired bleeding disorders; uncontrolled severe arterial hypertension; other gastrointestinal disease without active ulceration that can potentially lead to bleeding complications (e.g. inflammatory bowel disease, oesophagitis, gastritis and gastroesophageal reflux disease); vascular retinopathy; bronchiectasis or history of pulmonary bleeding.
Patients with prosthetic valves: Safety and efficacy of Xarelto have not been studied in patients with prosthetic heart valves; therefore, there are no data to support that Xarelto 20 mg (15 mg in patients with moderate or severe renal impairment) provides adequate anticoagulation in this patient population. Treatment with Xarelto is not recommended for these patients.
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.
Spinal/epidural anaesthesia or puncture: When neuraxial anaesthesia (spinal/epidural anaesthesia) or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long-term or permanent paralysis. The risk of these events may be increased by the post-operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. The risk may also be increased by traumatic or repeated epidural or spinal puncture. Patients are to be frequently monitored for signs and symptoms of neurological impairment (e.g. numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis.
At least 18 hours should elapse after the last administration of rivaroxaban before removal of an epidural catheter. Following removal of the catheter, at least 6 hours should elapse before the next rivaroxaban dose is administered.
If traumatic puncture occurs the administration of rivaroxaban is to be delayed for 24 hours.
Dosing recommendations before and after invasive procedures and surgical intervention: If an invasive procedure or surgical intervention is required, Xarelto 15 mg should be stopped at least 24 hours before the intervention, if possible and based on the clinical judgement 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 haemostasis has been established as determined by the treating physician (see Pharmacology: Pharmacokinetics under Actions).
Elderly population: Increasing age may increase haemorrhagic risk (see Pharmacology: Pharmacokinetics under Actions).
Information about excipients: Xarelto contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Xarelto has minor influence on the ability to drive and use machines. Adverse reactions like syncope (frequency: uncommon) and dizziness (frequency: common) have been reported (see Adverse Reactions). Patients experiencing these adverse reactions should not drive or use machines.