RIVAROXABAN

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 Rivaroxaban10 mg once daily, a dose of Rivaroxaban20 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 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, 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). 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 the recommended dose is necessary. 2). Hepatic impairment […]

4. 4. 1. 3 PHARMACEUTICAL FORM Film-coated tablet (tablet). 2 mm diameter) with “15” debossed on the one side. 2 mm diameter) with “20” debossed on the one side. 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 Rivaroxaban10 mg once daily, a dose of Rivaroxaban20 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 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, 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). 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 […]

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). 4 Special warnings and precautions for use 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 sub-groups 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). 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 and platelet aggregation inhibitors or selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs).

5). g. inflammatory bowel disease, oesophagitis, gastritis and gastroesophageal 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.

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 associated with an increased risk of bleeding during rivaroxaban therapy.

3). Patients with prosthetic valves Rivaroxaban should not be used for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement (TAVR). Safety and efficacy of rivaroxaban have not been studied in patients with prosthetic heart valves; therefore, there are no data to support that rivaroxaban provides adequate anticoagulation in this patient […]