RIVAROXABAN

5 mg twice daily. 5 mg twice daily 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 or a standard daily dose of ticlopidine. Treatment should be regularly evaluated in the individual patient weighing the risk for ischaemic events against the bleeding risks.

1). 5 mg film-coated tablets 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.

5 mg twice daily should also take a daily dose of 75 – 100 mg ASA. 1). Duration of treatment should be determined for each individual patient based on regular evaluations and should consider the risk for thrombotic events versus the bleeding risks.

5 mg twice daily should be evaluated depending on the type of event or procedure and antiplatelet regimen. 1). Missed dose 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 Xanirva When converting patients from VKAs to Xanirva, International Normalised Ratio (INR) values could be falsely elevated after the intake of Xanirva.

5). Converting from Xanirva to Vitamin K antagonists (VKA) There is a potential for inadequate anticoagulation during the transition from Xanirva to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant.

It should be noted that Xanirva can contribute to an elevated INR. 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. 2). g. g. intravenous unfractionated heparin).

Converting from Xanirva to parenteral anticoagulants Give the first dose of parenteral anticoagulant at the time the next Xanirva 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.

Summary of the safety profile The safety of rivaroxaban has been evaluated in thirteen pivotal phase III studies (see Table 1). Overall, 69,608 adult patients in nineteen phase III studies and 488 paediatric patients in two phase II and two phase III studies were exposed to rivaroxaban.

4 and ‘Description of selected adverse reactions’ below) (Table 2). 8%). 74 per 100 patient years***# * For all rivaroxaban studies all bleeding events are collected, reported and adjudicated. ** In the COMPASS study, there is a low anaemia incidence as a selective approach to adverse event collection was applied *** A selective approach to adverse event collection was applied # From the VOYAGER PAD study Tabulated list of adverse reactions The frequencies of adverse reactions reported with rivaroxaban in adult and paediatric patients are summarised in Table 3 below by system organ class (in MedDRA) and by frequency.

) Table 3: All adverse reactions reported in adult patients in phase III clinical studies or through post- marketing use* and in two phase II and two phase III studies in paediatric patients Common Uncommon Rare Very rare Not known Blood and lymphatic system disorders Anaemia (incl.

respective laboratory parameters) Thrombocytosis (incl. platelet count increased)A, thrombocytopenia Immune system disorders Allergic reaction, dermatitis allergic, angioedema and allergic oedema Anaphylactic reactions including anaphylactic shock Nervous system disorders Dizziness, headache Cerebral and intracranial haemorrhage, syncope Eye disorders Eye haemorrhage (incl.

conjunctival haemorrhage) Cardiac disorders Tachycardia Vascular disorders Hypotension, haematoma Respiratory, thoracic and mediastinal disorders Epistaxis, haemoptysis Eosinophilic pneumonia Gastrointestinal disorders Gingival bleeding, gastrointestinal tract haemorrhage (incl.

rectal haemorrhage), gastrointestinal and abdominal pains, dyspepsia, nausea, constipationA, diarrhoea, vomitingA Dry mouth Hepatobiliary disorders Increase in transaminases Hepatic impairment, increased bilirubin, increased blood alkaline phosphataseA, increased GGTA Jaundice, bilirubin conjugated increased (with or without concomitant increase of ALT), cholestasis, hepatitis (incl.

5 mg twice daily have been investigated in combination with the antiplatelet agents ASA alone or ASA plus clopidogrel/ticlopidine. 5 mg twice daily have been investigated in combination with ASA. 5 mg twice daily have been investigated in combination with the antiplatelet agent ASA alone or ASA plus short-term clopidogrel.

1). g. prasugrel or ticagrelor, has not been studied and is not recommended. Clinical surveillance in line with anticoagulation practice is recommended throughout the treatment period. Haemorrhagic risk As with other anticoagulants, patients taking Xanirva are to be carefully observed for signs of bleeding.

It is recommended to be used with caution in conditions with increased risk of haemorrhage. 9). e. epistaxis, gingival, gastrointestinal, genito urinary including abnormal vaginal or increased menstrual bleeding) and anaemia were seen more frequently during long term rivaroxaban treatment on top of single or dual anti-platelet therapy.

Thus, in addition to adequate clinical surveillance, laboratory testing of haemoglobin/haematocrit could be of value to detect occult bleeding and quantify the clinical relevance of overt bleeding, as judged to be appropriate. Several sub-groups of patients, as detailed below, are at increased risk of bleeding.

Therefore, the use of Xanirva in combination with dual antiplatelet therapy in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of atherothrombotic events. 8). Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site.

2). 6 fold on average) which may lead to an increased bleeding risk. Rivaroxaban is to be used with caution in patients with creatinine clearance 15 - 29 ml/min. 2). In patients with moderate renal impairment (creatinine clearance 30 - 49 ml/min) concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations.

1. 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.

g. 5). 4). 4). 2). 6).