RIVAROXABAN

Table 1:

Summary of posology per indication Indication Posology Method of administration Prevention of venous thromboembolism (VTE) in adults undergoing elective hip or knee replacement surgery. 10 mg rivaroxaban (2 ml of suspension) once daily with water (with or without food) Treatment of VTE and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing from 30 to 50 kg after at least 5 days of initial parenteral anticoagulation treatment.

15 mg rivaroxaban (3 ml of suspension) once daily with food Treatment of VTE and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing more than 50 kg after at least 5 days of initial parenteral anticoagulation treatment.

20 mg rivaroxaban (4 ml of suspension) once daily with food Prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack.

20 mg rivaroxaban (4 ml of suspension) once daily with food 15 mg rivaroxaban (3 ml of suspension) twice daily (day 1-21) Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

20 mg rivaroxaban (4 ml of suspension) once daily (day 22 onwards) with food Prevention of recurrent DVT and PE in adults (following completion of at least 6 months therapy for DVT or PE). 10 mg rivaroxaban (2 ml of suspension) once daily or 20 mg rivaroxaban (4 ml of suspension) once daily with water (with or without food) with food Prevention of stroke and systemic embolism in adults with moderate or severe renal impairment (creatinine clearance 15 – 49 ml/min).

15 mg rivaroxaban (3 ml of suspension) once daily with food 15 mg rivaroxaban (3 ml of suspension) twice daily (day 1-21) Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults with moderate or severe renal impairment (creatinine clearance 15 – 49 ml/min).

15 mg rivaroxaban (3 ml of suspension) once daily (day 22 onwards) with food Posology Prevention of VTE in adult patients undergoing elective hip or knee replacement surgery The recommended dose is 10 mg of rivaroxaban (2 ml of suspension) taken orally once daily.

Summary of the safety profile The safety of rivaroxaban has been evaluated in thirteen pivotal phase III studies (see Table 3). 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 4). 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 5 below by system organ class (in MedDRA) and by frequency.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare ( < 1/10 000), not known (cannot be estimated from the available data).

Table 5:

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.

Clinical surveillance in line with anticoagulation practice is recommended throughout the treatment period. Haemorrhagic risk As with other anticoagulants, patients taking Rivaroxaban 5 mg/ml Oral Suspension 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 compared with VKA treatment.

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.

8). In patients receiving Rivaroxaban 5 mg/ml Oral Suspension for VTE prevention following 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 haemoglobin.

Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site. g. 2). 1). The risk of bleeding should be carefully evaluated before and during therapy with rivaroxaban. 6 fold on average) which may lead to an increased bleeding risk.

Rivaroxaban 5 mg/ml Oral Suspension is to be used with caution in patients with creatinine clearance 15 - 29 ml/min. 2). 5). 73 m2), as no clinical data are available. g. ritonavir). 6 fold on average) which may lead to an increased bleeding risk.

5). 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 (ASA) and platelet aggregation inhibitors or selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

1. • Active clinically significant bleeding. • Lesions or conditions, 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). 2). 6).