Xarelto 2.5 mg

/ Bayer

The recommended dose is 2.5 mg twice daily.
Patients should also take a daily dose of 75 – 100 mg ASA or a daily dose of 75 – 100 mg ASA in addition to either a daily dose of 75 mg clopidogrel.
Treatment should be regularly evaluated in the individual patient weighing the risk for ischaemic events against the bleeding risks. Extension of treatment beyond 12 months should be done on an individual patient basis as experience up to 24 months is limited.
Treatment with Xarelto should be started as soon as possible after stabilisation of the ACS event (including revascularisation procedures); at the earliest 24 hours after admission to hospital and at the time when parenteral anticoagulation therapy would normally be discontinued.
If a dose is missed the patient should continue with the regular dose as recommended at the next scheduled time. The dose should not be doubled to make up for a missed dose.
Converting from Vitamin K Antagonists (VKA) to Xarelto: When converting patients from VKAs to rivaroxaban, International Normalized Ratio (INR) values will be falsely elevated after the intake of rivaroxaban. The INR is not valid to measure the anticoagulant activity of rivaroxaban, and therefore should not be used.
Converting from Xarelto to Vitamin K antagonists (VKA): There is a potential for inadequate anticoagulation during the transition from Xarelto to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that Xarelto can contribute to an elevated INR. In patients converting from Xarelto to VKA, VKA should be given concurrently until the INR is ≥ 2.0. For the first two days of the conversion period, standard initial dosing of VKA should be used followed by VKA dosing, as guided by INR testing. While patients are on both Xarelto and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Xarelto. Once Xarelto is discontinued INR testing may be done reliably at least 24 hours after the last dose.
Converting from parenteral anticoagulants to Xarelto: For patients currently receiving a parenteral anticoagulant, discontinue the parenteral anticoagulant and start Xarelto 0 to 2 hours before the time that the next scheduled administration of the parenteral medicinal product (e.g. low molecular weight heparins) would be due or at the time of discontinuation of a continuously administered parenteral medicinal product (e.g. intravenous unfractionated heparin).
Converting from Xarelto to parenteral anticoagulants: Give the first dose of parenteral anticoagulant at the time the next Xarelto dose would be taken.
Special populations
Renal impairment: Limited clinical data for patients with severe renal impairment (creatinine clearance 15 – 29 ml/min) indicate that rivaroxaban plasma concentrations are significantly increased. Therefore, Xarelto is to be used with caution in these patients. Use is not recommended in patients with creatinine clearance < 15 ml/min. No dose adjustment is necessary in patients with mild renal impairment (creatinine clearance 50 – 80 ml/min) or moderate renal impairment (creatinine clearance 30 – 49 ml/min).
Hepatic impairment: Xarelto is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C.
Elderly population: No dose adjustment.
Body weight: No dose adjustment.
Gender: No dose adjustment.
Paediatric population: The safety and efficacy of Xarelto in children aged 0 to 18 years have not been established. No data are available. Therefore, Xarelto is not recommended for use in children below 18 years of age.
Method of administration: For oral use. Xarelto can be taken with or without food. For patients who are unable to swallow whole tablets, Xarelto tablet may be crushed and mixed with water or apple puree immediately prior to use and administered orally. The crushed Xarelto tablet may also be given through gastric tubes after confirmation of the correct gastric placement of the tube. The crushed tablet should be administered in a small amount of water via a gastric tube after which it should be flushed with water.

Co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers.

Hypersensitivity to the active substance or to any of the excipients. Active clinically significant bleeding. Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban, etc.) except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter. Concomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke or a transient ischaemic attack (TIA). Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C. Pregnancy and breast feeding.

Efficacy and safety of Xarelto has been investigated in combination with the antiplatelet agents aspirin and clopidogrel. Treatment in combination with other antiplatelet agents, e.g. prasugrel or ticagrelor, has not been studied and is not recommended.
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.
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. In patients with moderate renal impairment (creatinine clearance 30 – 49 ml/min) concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations Xarelto is to be used with caution.
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.
It should be used with caution in ACS patients: > 75 years of age if co-administered with ASA alone or with ASA plus clopidogrel, patients with low body weight (< 60 kg) if co-administered with ASA alone or with ASA plus clopidogrel.
Patients with prosthetic valves: Safety and efficacy of Xarelto have not been studied in patients with prosthetic heart valves; herefore,Treatment with Xarelto is not recommended for these patients.
Patients with prior stroke or TIA: Xarelto 2.5 mg is contraindicated for the treatment of ACS in patients with a prior stroke or TIA.
Spinal/epidural anaesthesia or puncture: Epidural or spinal hematomas have occurred in patients treated with XARELTO who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures.
Invasive procedures and surgical intervention: Xarelto 2.5 mg should be stopped at least 12 hours before the intervention, if possible and based on the clinical judgement of the physician.
Elderly population: Increasing age may increase haemorrhagic risk.
Dermatological reactions: Serious skin reactions, including Stevens-Johnson syndrome/Toxic Epidermal Necrolysis, have been reported during post-marketing surveillance in association with the use of rivaroxaban.
Lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including XARELTO, increases the risk of thrombotic events. If anticoagulation with XARELTO is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant
For full details see prescribing information.

(Common): Blood and lymphatic system disorders: Anaemia (incl. respective laboratory parameters). Nervous system disorders: Dizziness, headache. Eye disorders: Eye haemorrhage (incl. conjunctival haemorrhage). Vascular disorders: Hypotension, haematoma. Respiratory, thoracic and mediastinal disorders: Epistaxis, haemoptysis. Gastrointestinal disorders: Gingival bleeding, gastrointestinal tract haemorrhage (incl. rectal haemorrhage), gastrointestinal and abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting. Skin and subcutaneous tissue disorders: Pruritus (incl. uncommon cases of generalised pruritus), rash, ecchymosis, cutaneous and subcutaneous haemorrhage. Musculoskeletal and connective tissue disorders: Pain in extremity. Renal and urinary disorders: Urogenital tract haemorrhage (incl. haematuria and menorrhagia), renal impairment (incl. blood creatinine increased, blood urea increased). General disorders and administration site conditions: Fever, peripheral oedema, decreased general strength and energy (incl. fatigue and asthenia). Investigations: Increase in transaminases. Injury, poisoning and procedural complications: Postprocedural haemorrhage (incl. postoperative anaemia, and wound haemorrhage), contusion, wound secretion.
For full details see prescribing information.

CYP3A4 and P-gp inhibitors: 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.
Anticoagulants: Due to the increased bleeding risk care is to be taken if patients are treated concomitantly with any other anticoagulants.
NSAIDs/platelet aggregation inhibitors: Care is to be taken if patients are treated concomitantly with NSAIDs (including acetylsalicylic acid) and platelet aggregation inhibitors because these medicinal products typically increase the bleeding risk.
SSRIs/SNRIs: As with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets.
Warfarin: No pharmacokinetic interaction was observed between warfarin and rivaroxaban.
CYP3A4 inducers: Concomitant administration of strong CYP3A4 inducers should be avoided unless the patient is closely observed for signs and symptoms of thrombosis.
For full details see prescribing information.

Pregnancy: Safety and efficacy of Xarelto have not been established in pregnant women. Due to the potential reproductive toxicity, the intrinsic risk of bleeding and the evidence that rivaroxaban passes the placenta, Xarelto is contraindicated during pregnancy. Women of child-bearing potential should avoid becoming pregnant during treatment with rivaroxaban.
Lactation: Safety and efficacy of Xarelto have not been established in breast feeding women. Xarelto is contraindicated during breast feeding.
For full details see prescribing information.

Rare cases of overdose up to 600 mg have been reported without bleeding complications or other adverse reactions. Due to limited absorption a ceiling effect with no further increase in average plasma exposure is expected at supratherapeutic doses of 50 mg rivaroxaban or above.
For full details see prescribing information.

Storage: It is recommended to store at room temprature.