RIVAROXABAN TILLOMED

Posology Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE 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 Tillomed 20 mg once daily should be considered.

4). 5). For patients with moderate or severe renal impairment where the decision has been taken for 15 mg once daily from Day 22 onwards, other pack sizes only containing 15 mg film-coated tablets are available (see dosing instructions in section “Special populations” below).

If a dose is missed during the 15 mg twice daily treatment phase (day 1 - 21), the patient should take Rivaroxaban Tillomed 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 Tillomed 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. 5. When converting patients from VKAs to Rivaroxaban Tillomed, INR values will be falsely elevated after the intake of Rivaroxaban Tillomed. 5). Converting from Rivaroxaban Tillomed to Vitamin K antagonists (VKA) There is a potential for inadequate anticoagulation during the transition from Rivaroxaban Tillomed to VKA.

Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that Rivaroxaban Tillomed 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.

While patients are on both Rivaroxaban Tillomed and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Rivaroxaban Tillomed. 2). g. g. intravenous unfractionated heparin). Converting from Rivaroxaban Tillomed to parenteral anticoagulants Give the first dose of parenteral anticoagulant at the time the next Rivaroxaban Tillomed 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, Rivaroxaban Tillomed is to be used with caution in these patients.

2). In patients with moderate (creatinine clearance 30 - 49 ml/min) or severe (creatinine clearance 15- 29 ml/min) renal impairment the following dose recommendations apply: - For the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE, patients should be treated with 15 mg twice daily for the first 3 weeks.

Thereafter, when the recommended dose is 20 mg once daily, a reduction of the dose from 20 mg once daily to 15 mg once daily should be considered if the patient’s assessed risk for bleeding outweighs the risk for recurrent DVT and PE.

2). When the recommended dose is 10 mg once daily, no dose adjustment from […]

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 increase)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, Dry mouth gastrointestina l tract haemorrhage (incl.

rectal haemorrhage), gastrointestina l and abdominal pains, dyspepsia, nausea, constipationA , diarrhoea, vomitingA 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.

hepatocellular injury) Skin and subcutaneous tissue disorders Pruritus (incl. uncommon cases of generalised pruritus), rash, ecchymosis, cutaneous and subcutaneous haemorrhage Urticaria Stevens-Johnson syndrome/Toxic Epidermal Necrolysis, DRESS syndrome Musculoskeletal and connective tissue disorders Pain in extremityA Haemarthrosis Muscle haemorrhage Compartment syndrome secondary to a bleeding Renal and urinary disorders Urogenital tract haemorrhage (incl.

haematuria and menorrhagiaB) , renal impairment (incl. blood creatinine increased, blood urea increased) Renal failure/acute renal failure secondary to a bleeding sufficient to cause hypoperfusion, Anticoagulant- related nephropathy General disorders and administration site conditions FeverA, peripheral […]

1 Therapeutic indications Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. 2 Posology and method of administration Posology Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE 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 Tillomed 20 mg once daily should be considered.

4). 5). For patients with moderate or severe renal impairment where the decision has been taken for 15 mg once daily from Day 22 onwards, other pack sizes only containing 15 mg film-coated tablets are available (see dosing instructions in section “Special populations” below).

If a dose is missed during the 15 mg twice daily treatment phase (day 1 - 21), the patient should take Rivaroxaban Tillomed 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 Tillomed 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. 5. When converting patients from VKAs to Rivaroxaban Tillomed, INR values will be falsely elevated after the intake of Rivaroxaban Tillomed. 5). Converting from Rivaroxaban Tillomed to Vitamin K antagonists (VKA) There is a potential for inadequate anticoagulation during the transition from Rivaroxaban Tillomed to VKA.

Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that Rivaroxaban Tillomed 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.

While patients are on both Rivaroxaban Tillomed and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Rivaroxaban Tillomed. 2). g. g. intravenous unfractionated heparin). Converting from Rivaroxaban Tillomed to parenteral anticoagulants Give the first dose of parenteral anticoagulant at the time the next Rivaroxaban Tillomed 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, Rivaroxaban Tillomed is to be used with caution in these patients.

2). In patients with moderate (creatinine clearance 30 - […]

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). 2). 6).