RIVAROXABAN DR REDDYS

Posology Prevention of VTE in adult patients undergoing elective hip or knee replacement surgery The recommended dose is 10 mg rivaroxaban taken orally once daily. The initial dose should be taken 6 to 10 hours after surgery, provided that haemostasis has been established.

The duration of treatment depends on the individual risk of the patient for venous thromboembolism which is determined by the type of orthopaedic surgery. • For patients undergoing major hip surgery, a treatment duration of 5 weeks is recommended.

• For patients undergoing major knee surgery, a treatment duration of 2 weeks is recommended. If a dose is missed the patient should take rivaroxaban immediately and then continue the following day with once daily intake as before. 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 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 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 10 mg once daily or 20 mg once daily 10 mg or 20 mg 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.

5. When converting patients from VKAs to rivaroxaban, International Normalised Ratio (INR) values will be falsely elevated after the intake of rivaroxaban. 5). Converting from rivaroxaban to Vitamin K antagonists (VKA) There is a potential for inadequate anticoagulation during the transition from rivaroxaban to VKA.

Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that rivaroxaban 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 and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of rivaroxaban. 2). g. g. intravenous unfractionated heparin). Converting from rivaroxaban to parenteral anticoagulants Give the first dose of parenteral anticoagulant at the time the next rivaroxaban 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 is to be used with caution in these patients.

2). 2). - For the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE, no dose adjustment from the recommended dose is necessary in patients with mild renal impairment (creatinine clearance 50 - 80 ml/min) […]

Summary of the safety profile The safety of rivaroxaban has been evaluated in thirteen phase III studies including 53,103 patients exposed to rivaroxaban (see Table 1). 4. and ‘Description of selected adverse reactions’ below) (Table 2).

8 %). 15 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 Tabulated list of adverse reactions The frequencies of adverse reactions reported with rivaroxaban 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 patients in phase III clinical trials or through post- marketing use* 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 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.

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 General disorders and administration site conditions FeverA, peripheral- oedema, decreased general strength and energy (incl.

fatigue and asthenia) Feeling unwell (incl. malaise) Localised oedemaA Investigations Increase in transaminases increased LDHA, increased lipaseA, increased amylaseA, Injury, poisoning and procedural complications Postprocedural haemorrhage (incl.

postoperative anaemia, and wound haemorrhage), contusion, wound secretionA Vascular pseudoaneurysmC A: observed in prevention of VTE in adult patients undergoing elective hip or knee replacement surgery B: observed in treatment of DVT, PE and prevention of recurrence as very common in women < 55 years C: observed as uncommon in prevention of atherothrombotic events in patients after an ACS (following percutaneous coronary intervention) *A pre-specified selective approach to adverse event collection was applied.

As incidence of adverse reactions did not increase and no new adverse reaction was identified, COMPASS study data were not included for frequency calculation in this table. Description of selected adverse reactions Due to the pharmacological mode of […]

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

1). Patients treated with rivaroxaban and antiplatelet agents should only receive concomitant treatment with NSAIDs if the benefit outweighs the bleeding risk. g. inflammatory bowel disease, oesophagitis, gastritis and gastroesophageal reflux disease) • vascular retinopathy • bronchiectasis or history of pulmonary bleeding It should be used with caution in ACS and CAD/PAD patients: • ≥ 75 years of age if co-administered with ASA alone or with ASA plus clopidogrel or ticlopidine.

The benefit-risk of the treatment should be individually assessed on a regular basis. • with lower body weight (< 60 kg) if co-administered with ASA alone or with ASA plus clopidogrel or ticlopidine • CAD patients with severe symptomatic heart failure.

1). Patients with cancer Patients with malignant disease may simultaneously be at higher risk of bleeding and thrombosis. The individual benefit of antithrombotic treatment should be weighed against risk for bleeding in patients with active cancer dependent on tumour location, antineoplastic therapy and stage of disease.

Tumours located in the gastrointestinal or genitourinary tract have been […]

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).