RIVAROXABAN MILPHARM

Posology Prevention of stroke and systemic embolism in adults The recommended dose is 20 mg once daily, which is also the recommended maximum dose. 4). If a dose is missed the patient should take Rivaroxaban immediately and continue on the following day with the once daily intake as recommended.

The dose should not be doubled within the same day to make up for a missed dose. Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE in adults The recommended dose for the initial treatment of acute DVT or PE is 15 mg twice daily for the first three weeks followed by 20 mg once daily for the continued treatment and prevention of recurrent DVT and PE.

e. recent major surgery or trauma). Longer duration of therapy should be considered in patients with provoked DVT or PE not related to major transient risk factors, unprovoked DVT or PE, or a history of recurrent DVT or PE. When extended prevention of recurrent DVT and PE is indicated (following completion of at least 6 months therapy for DVT or PE), the recommended dose is 10 mg once daily.

In patients in whom the risk of recurrent DVT or PE is considered high, such as those with complicated comorbidities, or who have developed recurrent DVT or PE on extended prevention with Rivaroxaban 10 mg once daily, a dose of Rivaroxaban 20 mg once daily should be considered.

4). Time period Dosing schedule Total daily dose Day 1-21 15 mg twice daily 30 mgTreatment and prevention of recurrent DVT and PE Day 22 and onwards 20 mg once daily 20 mg Prevention of recurrent DVT and PE Following Completion of at least 6 months therapy for DVT or PE 10mg once daily or 20mg once daily 10mg or 20mg To support the dose switch from 15 mg to 20 mg after Day 21 a first 4 weeks treatment initiation pack of Rivaroxaban for treatment of DVT/PE is available.

If a dose is missed during the 15 mg twice daily treatment phase (day 1 21), the patient should take Rivaroxaban immediately to ensure intake of 30 mg rivaroxaban per day. In this case two 15 mg tablets may be taken at once. The patient should continue with the regular 15 mg twice daily intake as recommended on the following day.

If a dose is missed during the once daily treatment phase, the patient should take Rivaroxaban immediately, and continue on the following day with the once daily intake as recommended. The dose should not be doubled within the same day to make up for a missed dose.

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.

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 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 Anaphylact ic reactions including anaphylacti c 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, Eosinophili haemoptysis c pneumonia Gastrointestinal disorders Gingival bleeding, gastrointestinal tract haemorrhage (incl.

Clinical surveillance in line with anticoagulation practice is recommended throughout the treatment period. Haemorrhagic risk As with other anticoagulants, patients taking rivaroxaban 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 subgroups of patients, as detailed below, are at increased risk of bleeding.

8). Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site. 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 is to be used with caution in patients with creatinine clearance 15-29 ml/min. 2). 5). 73 m2), as no clinical data is available. g. ritonavir). 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 and platelet aggregation inhibitors or selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs).

5). g. inflammatory bowel disease, oesophagitis, gastritis and gastro-esophageal reflux disease) • Vascular retinopathy • Bronchiectasis or history of pulmonary bleeding. Patients with cancer Patients with malignant disease may simultaneously be at higher risk of bleeding and thrombosis.

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 intra-spinal or intracerebral vascular abnormalities.

g. 5). 2). 6).