Rivaroxaban Viatris (Previously Rivaroxaban Mylan)

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) 12 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 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 Jaundice, Bilirubin conjugated increased (with or without 13 Common Uncommon Rare Very rare Not known phosphataseA, Increased GGTA 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 […]

4. 1. 3. 4 mm diameter) marked with “RX” on one side of the tablet and “1” on the other side. 4. 1). Rivaroxaban Viatris co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events.

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). Treatment with Rivaroxaban Viatris 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 Rivaroxaban Viatris When converting patients from VKAs to Rivaroxaban Viatris, International Normalised Ratio (INR) values could be falsely elevated after the intake of Rivaroxaban Viatris.

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

It should be noted that Rivaroxaban Viatris 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 Viatris and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Rivaroxaban Viatris.

2). g. g. intravenous unfractionated heparin). Converting from Rivaroxaban Viatris to parenteral anticoagulants Give the first dose of parenteral anticoagulant at the time the next Rivaroxaban Viatris dose would be taken. Special populations Renal impairment 4 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 Viatris is to be used with caution in these patients. 2). 2). Hepatic impairment Rivaroxaban Viatris is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients […]

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).