APIXABAN

5ml) taken orally twice daily. The initial dose should be taken 12 to 24 hours after surgery. Physicians may consider the potential benefits of earlier anticoagulation for VTE prophylaxis as well as the risks of post-surgical bleeding in deciding on the time of administration within this time window.

In patients undergoing hip replacement surgery The recommended duration of treatment is 32 to 38 days. In patients undergoing knee replacement surgery The recommended duration of treatment is 10 to 14 days. Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) The recommended dose of apixaban is 5 mg (5 ml) taken orally twice daily.

5 mg/dL (133 micromole/L). Therapy should be continued long-term. Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt) The recommended dose of apixaban for the treatment of acute DVT and treatment of PE is 10 mg (10 ml) taken orally twice daily for the first 7 days followed by 5 mg taken orally twice daily.

, recent surgery, trauma, immobilisation). 5 ml) taken orally twice daily. 4). Missed dose If a dose is missed, the patient should take Apixaban immediately and then continue with twice daily intake as before. 5). These medicinal products should not be administered simultaneously.

Switching from vitamin K antagonist (VKA) therapy to Apixaban When converting patients from vitamin K antagonist (VKA) therapy to Apixaban, warfarin or other VKA therapy should be discontinued and Apixaban started when the international normalised ratio (INR) is < 2.

Switching from Apixaban to VKA therapy When converting patients from Apixaban to VKA therapy, administration of Apixaban should be continued for at least 2 days after beginning VKA therapy. After 2 days of coadministration of Apixaban with VKA therapy, an INR should be obtained prior to the next scheduled dose of Apixaban.

Coadministration of Apixaban and VKA therapy should be continued until the INR is ≥ 2. 2). 2). 2). 5 mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg, a dose reduction is necessary and described above. 2). 5 ml) twice daily.

2). 3). 4. 2). It should be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). 2). 5 x ULN were excluded in clinical studies. 2). Prior to initiating Apixaban, liver function testing should be performed.

2). NVAF - No dose adjustment required, unless […]

1). Common adverse reactions were haemorrhage, contusion, epistaxis, and haematoma (see Table 2 for adverse reaction profile and frequencies by indication). 5 mg twice daily experienced adverse reactions. The overall incidence of adverse reactions related to bleeding with apixaban was 10% in the apixaban vs enoxaparin studies.

6% in the apixaban vs acetylsalicylic acid study. 76%/year. 18%/year. 1). Tabulated list of adverse reactions Table 2 shows the adverse reactions ranked under headings of system organ class and frequency using the following convention: 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) for VTEp, NVAF and VTEt respectively.

, haemorrhagic stroke or putamen, cerebellar, intraventricular, or subdural haemorrhages). Description of selected adverse reactions The use of apixaban may be associated with an increased risk of occult or overt bleeding from any tissue or organ, which may result in posthaemorrhagic anaemia.

1). Known complications secondary to severe bleeding such as anticoagulant- related nephropathy has occasionally been reported in patients receiving anticoagulants in the post-marketing setting. In patients with pre-existing kidney disease, ARN may occur, possibly in relation to episodes of excessive anticoagulation and haematuria.

4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is […]

Haemorrhage risk As with other anticoagulants, patients taking apixaban 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). 1). An agent to reverse the anti-factor Xa activity of apixaban is available.

3). 5). Care is to be taken if patients are treated concomitantly with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), or non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid.

5). In patients with atrial fibrillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with Apixaban.

6% per year. 1). A clinical study enrolled patients with atrial fibrillation with ACS and/or undergoing PCI and a planned treatment period with a P2Y12 inhibitor, with or without ASA, and oral anticoagulant (either apixaban or VKA) for 6 months.

1). 04% per year). 5). Patients with prosthetic heart valves Safety and efficacy of apixaban have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of apixaban is not recommended in this setting.

Patients with antiphospholipid syndrome Direct acting Oral Anticoagulants (DOACs) including apixaban are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome. In particular for patients that are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies), treatment with DOACs could be associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

Surgery and invasive procedures Apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleeding. This includes interventions for which the probability of clinically significant bleeding cannot be excluded or for which the risk of bleeding would be unacceptable.

Apixaban should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. This includes interventions for which any bleeding that occurs is expected to be minimal, non-critical in its location or easily controlled.

If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. This risk of bleeding should be weighed against the urgency of intervention. 2). 5).

Temporary discontinuation Discontinuing anticoagulants, including apixaban, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Lapses in therapy should be avoided and if anticoagulation with apixaban must be temporarily discontinued for any reason, therapy should be restarted as soon as possible.

Spinal/epidural anaesthesia or puncture When neuraxial anaesthesia (spinal/epidural anaesthesia) or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long-term or permanent paralysis.

The risk of these events may be increased by the post-operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the first dose of apixaban.

The risk may also be increased by […]

1. • Active clinically significant bleeding. 2). • Lesion or condition if considered a significant risk factor 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.

5).