APIXABAN MYLAN

5 mg 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 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 taken orally twice daily for the first 7 days followed by 5 mg taken orally twice daily.

g. recent surgery, trauma, immobilisation). 5 mg taken orally twice daily. 1). 4). Missed dose If a dose is missed, the patient should take Apixaban Mylan 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 Mylan When converting patients from vitamin K antagonist (VKA) therapy to Apixaban Mylan, warfarin or other VKA therapy should be discontinued and Apixaban Mylan started when the international normalised ratio (INR) is < 2.

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

Coadministration of Apixaban Mylan 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 mg 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 Mylan, liver function testing should be performed.

2). NVAF - No dose adjustment required, unless criteria for dose reduction are met […]

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.

Table 2:

Tabulated adverse reactions System Organ Class Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp) Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF) Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt) Blood and lymphatic system disorders Anaemia Common Common Common Thrombocytopenia Uncommon Uncommon Common Immune system disorders Hypersensitivity, allergic oedema and Anaphylaxis Rare Uncommon Uncommon Pruritus Uncommon Uncommon Uncommon* Angioedema Not known Not known Not known Nervous system disorders Brain haemorrhage† Not known Uncommon Rare System Organ Class Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp) Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF) Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt) Eye disorders Eye haemorrhage (including conjunctival haemorrhage) Rare Common Uncommon Vascular disorders Haemorrhage, haematoma Common Common Common Hypotension (including procedural hypotension) Uncommon Common Uncommon Intra-abdominal haemorrhage Not known Uncommon Not known Respiratory, thoracic and mediastinal disorders Epistaxis Uncommon Common Common Haemoptysis Rare Uncommon Uncommon Respiratory tract haemorrhage Not known Rare Rare Gastrointestinal disorders Nausea Common Common Common Gastrointestinal haemorrhage Uncommon Common Common Haemorrhoidal haemorrhage Not known Uncommon Uncommon Mouth haemorrhage Not known Uncommon Common Haematochezia Uncommon Uncommon Uncommon Rectal haemorrhage, gingival bleeding Rare Common Common Retroperitoneal haemorrhage Not known Rare Not known Hepatobiliary disorders Liver function test abnormal, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased Uncommon Uncommon Uncommon Gamma-glutamyltransferase Uncommon Common Common System Organ Class Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp) Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF) Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt) increased Alanine aminotransferase increased Uncommon Uncommon Common Skin and subcutaneous tissue disorders Skin rash Not known Uncommon Common Alopecia Rare Uncommon Uncommon Erythema multiforme Not known Very rare Not known Cutaneous vasculitis Not known Not known Not known Musculoskeletal and connective tissue disorders Muscle haemorrhage Rare Rare Uncommon Hemarthrosis Not known Not known Not known Renal and urinary disorders Haematuria Uncommon Common Common Anticoagulant-related nephropathy Not known Not known Not known Reproductive system and breast disorders Abnormal vaginal haemorrhage, urogenital haemorrhage Uncommon Uncommon Common General disorders and administration site conditions Application site bleeding Not known Uncommon Uncommon Investigations Occult blood positive Not known Uncommon Uncommon Injury, poisoning and procedural complications Contusion Common Common Common System Organ Class Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp) Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF) Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt) Post procedural haemorrhage (including post procedural haematoma, wound haemorrhage, vessel puncture site haematoma and catheter site haemorrhage), wound secretion, incision site haemorrhage (including incision site haematoma), operative haemorrhage Uncommon Uncommon Uncommon Traumatic haemorrhage Not known Uncommon Uncommon * There were no occurrences of generalised pruritus in CV185057 (long term prevention of VTE).

e. haemorrhagic stroke or putamen, cerebellar, intraventricular, or subdural haemorrhages). The use of […]

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). g. 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 2glycoprotein 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 Mylan 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 Mylan 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 […]

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.

g. 5).