APIXABAN MYLAN

Posology 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. 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). 2). 2). 5). Patients undergoing cardioversion Apixaban Mylan can be initiated or continued in NVAF patients who may require cardioversion. g. transesophageal echocardiography (TEE) or computed tomographic scan (CT)) prior to cardioversion should be considered, in accordance with established medical guidelines.

5 days (5 single […]

1). Common adverse reactions were haemorrhage, contusion, epistaxis, and haematoma (see Table 2 for adverse reaction profile and frequencies by indication). 6% in the apixaban vs acetylsalicylic acid study. 76%/year. 18%/year. 1). from the available data) for NVAF and VTEt respectively.

Table 2:

Tabulated adverse reactions System Organ Class 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) System Organ Class 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 Thrombocytopenia Uncommon Common Immune system disorders Hypersensitivity, allergic oedema and Anaphylaxis Uncommon Uncommon Pruritus Uncommon Uncommon* Angioedema Not known Not known Nervous system disorders Brain haemorrhage† Uncommon Rare Eye disorders Eye haemorrhage (including conjunctival haemorrhage) Common Uncommon Vascular disorders Haemorrhage, haematoma Common Common Hypotension (including procedural hypotension) Common Uncommon Intra-abdominal haemorrhage Uncommon Not known Respiratory, thoracic and mediastinal disorders Epistaxis Common Common Haemoptysis Uncommon Uncommon Respiratory tract haemorrhage Rare Rare Gastrointestinal disorders Nausea Common Common Gastrointestinal haemorrhage Common Common Haemorrhoidal haemorrhage Uncommon Uncommon Mouth haemorrhage Uncommon Common Haematochezia Uncommon Uncommon Rectal haemorrhage, gingival bleeding Common Common System Organ Class 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) Retroperitoneal haemorrhage Rare Not known Hepatobiliary disorders Liver function test abnormal, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased Uncommon Uncommon Gamma-glutamyltransferase increased Common Common Alanine aminotransferase increased Uncommon Common Skin and subcutaneous tissue disorders Skin rash Uncommon Common Alopecia Uncommon Uncommon Erythema multiforme Very rare Not known Cutaneous vasculitis Not known Not known Musculoskeletal and connective tissue disorders Muscle haemorrhage Rare Uncommon Hemarthrosis Not known Not known Renal and urinary disorders Haematuria Common Common Anticoagulant-related nephropathy Not known Not known Reproductive system and breast disorders Abnormal vaginal haemorrhage, urogenital haemorrhage Uncommon Common General disorders and administration site conditions Application site bleeding Uncommon Uncommon Investigations Occult blood positive Uncommon Uncommon Injury, poisoning and procedural complications Contusion Common Common System Organ Class 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 Traumatic haemorrhage 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 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). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 Mylan.

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.

Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy Apixaban Mylan is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and efficacy of apixaban have not been established in these clinical situations.

Patients with active cancer Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefits […]

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).