GENERIC NAME: Apixaban 2.5 mg film-coated tablets.
PRESENTATION: Each film-coated tablet contains 2.5 mg apixaban. Carton box containing 2 blisters, each of 10 film coated tablets.
INDICATIONS: (1) Prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. (VTEp) (2) Prevention of stroke and systemic embolism in adult patients with non- valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischemic attack (TIA); age≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II). (3) Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. (VTEt)
DOSAGE AND ADMINISTRATION: Oral use. Eliquis should be swallowed with water, with or without food. Crushed Eliquis tablets are stable in water, 5% glucose in water (G5W), apple juice, and apple puree for up to 4 hours.
Prevention of VTE in elective hip or knee replacement surgery (VTEp): The recommended dose of apixaban is 2.5 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. The recommended duration of treatment is 32 to 38 days (In patients undergoing hip replacement surgery) or 10 to 14 days (in patients undergoing knee replacement surgery). 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. Dose reduction: The recommended dose of apixaban is 2.5 mg taken orally twice daily in patients with NVAF and at least two of the following characteristics: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL (133 micromole/L). Therapy should be continued long-term. 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. Patients can continue apixaban use while undergoing catheter ablation. Apixaban can be initiated or continued in NVAF patients who may require cardioversion. There is limited experience of treatment with apixaban at the recommended dose for NVAF patients when used in combination with antiplatelet agents in patients with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) after hemostasis is achieved. 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. 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. As per available medical guidelines, short duration of treatment (at least 3 months) should be based on transient risk factors (e.g., recent surgery, trauma, immobilization). The recommended dose of apixaban for the prevention of recurrent DVT and PE is 2.5 mg taken orally twice daily. When prevention of recurrent DVT and PE is indicated, the 2.5 mg twice daily dose should be initiated following completion of 6 months of treatment with apixaban 5 mg twice daily or with another anticoagulant. The duration of overall therapy should be individualized after careful assessment of the treatment benefit against the risk for bleeding.
Pediatric population: The safety and efficacy of Eliquis in children and adolescents below age 18 have not been established.
Patients with renal impairment: In patients with mild (creatinine clearance 51-80 mL/min) or moderate (creatinine clearance 30-50 mL/min) renal impairment, the following recommendations apply: * for VTEp and VTEt - No dose adjustment is necessary; * for NVAF and serumcreatinine ≥ 1.5mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg, a dose reduction is necessary and described above. In the absence of other criteria for dose reduction (age, body weight), no dose adjustment is necessary. In patients
with severe renal impairment (creatinine clearance 15-29 mL/min) the following recommendations apply: * for VTEp and VTEt - apixaban is to be used with caution. * for NVAF - patients should receive the lower dose of apixaban 2.5 mg twice daily. In patients with creatinine clearance < 15 mL/min, or in patients undergoing dialysis, apixaban is not recommended.
Patients with hepatic impairment: Prior to initiating apixaban, liver function testing should be performed. It is not recommended in patients with severe hepatic impairment. It should be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). Apixaban should be used with cautiously in patients with elevated liver enzymes ALT/AST > 2 x ULN or total bilirubin ≥ 1.5 x ULN.
Elderly patients/Body weight: VTEp and VTEt - No dose adjustment required. NVAF – No dose adjustment required, unless criteria for dose reduction are met. Coadministration of apixaban with ASA in elderly patients should be used cautiously. Low body weight (< 60 kg) may increase hemorrhagic risk.
Gender: No dose adjustment required.
Pregnancy: It is preferable to avoid the use of apixaban during pregnancy. It is unknown whether apixaban or its metabolites are excreted in human milk.
Breast-feeding: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from apixaban therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
CONTRAINDICATIONS: * Hypersensitivity to the active substance or to any of the excipients. * Active clinically significant bleeding. * Hepatic disease associated with coagulopathy and clinically relevant bleeding risk. * Lesion or condition if considered a significant risk factor for major bleeding. * Concomitant treatment with any other anticoagulant agent except under specific circumstances of switching anticoagulant therapy, when unfractionated heparin (UFH) is given at doses necessary to maintain an open central venous or arterial catheter, or when UFH is given during catheter ablation for atrial fibrillation.
WARNING AND PRECAUTIONS:
Hemorrhage risk: 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 hemorrhage. Apixaban administration should be discontinued if severe hemorrhage occurs.
Use of thrombolytic agents for the treatment of acute ischemic stroke: There is very limited experience with the use of thrombolytic agents for the treatment of acute ischemic stroke in patients administered apixaban.
Patients with prosthetic heart valves: The use of apixaban is not recommended in this setting.
Patients with antiphospholipid syndrome: Direct oral anticoagulants (DOACs) including apixaban are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome.
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, and at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. Apixaban should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate hemostasis has been established. For patients undergoing catheter ablation for atrial fibrillation, apixaban treatment does not need to be Interrupted.
Temporary discontinuation: Discontinuing anticoagulants, including apixaban, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis.
Spinal/epidural anesthesia or puncture: When neuraxial anesthesia (spinal/epidural anesthesia) 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 hematoma which can result in long-term or permanent paralysis. Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the first dose of apixaban. Patients are to be frequently monitored for signs and symptoms of neurological impairment.
Hemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Apixaban is not recommended as an alternative to UFH in patients with pulmonary embolism who are hemodynamically unstable or may receive thrombolysis or pulmonary embolectomy.
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 against the risks should be made.
Patients undergoing hip fracture surgery: Apixaban is not recommended in these patients.
Laboratory parameters: Clotting tests are affected as expected by the mechanism of action of apixaban.
Information about excipients: Eliquis contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially "sodium-free".
Interaction with other medicinal products affecting hemostasis: Concomitant treatment with any other anticoagulants is contraindicated. The concomitant use of apixaban with antiplatelet agents increases the risk of bleeding. 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 medicinal products (NSAIDs), including acetylsalicylic acid. There is limited experience of coadministration with other platelet aggregation inhibitors or thrombolytic agents. As such agents increase the bleeding risk, co-administration of these medicinal products with apixaban is not recommended.
Interaction with inhibitors of both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (Pgp): Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp.
Interaction with inducers of both CYP3A4 and P-gp: In patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp the following recommendations apply: * for VTEp and NVAF - Apixaban should be used with caution; * for VTEt - Apixaban should not be used.
OVERDOSE: Overdose of apixaban may result in a higher risk of bleeding. In the event of hemorrhagic complications, treatment must be discontinued, and the source of bleeding investigated. The initiation of appropriate treatment, e.g., surgical hemostasis, the transfusion of fresh frozen plasma or the administration of a reversal agent for factor Xa inhibitors should be considered. An agent to reverse the anti-factor Xa activity of apixaban is available. Hemodialysis is unlikely to be an effective means of managing apixaban overdose. Activated charcoal may be useful in the management of apixaban overdose or accidental ingestion.
ADVERSE REACTION: Common adverse reactions include: hemorrhage, hematoma, contusion, epistaxis (with NVAF, VTEt), anemia, thrombocytopenia (with VTEt), eye hemorrhage including conjunctival hemorrhage (with NVAF), hypotension (with NVAF), nausea, gastrointestinal hemorrhage (with NVAF, VTEt), mouth hemorrhage (with VTEt), rectal hemorrhage and gingival bleeding (with NVAF, VTEt), gamma-glutamyl transferase increased (with NVAF, VTEt), alanine aminotransferase increased (with VTEt), skin rash (with VTEt), hematuria (with NVAF, VTEt), abnormal vaginal hemorrhage and urogenital hemorrhage (with VTEt).
PHARMACEUTICAL PRECAUTIONS: Shelf Life: 36 months. Do not use Eliquis after the expiry date which is stated on the carton after EXP:. Store at temperature not exceeding 30 °C. Keep out of the sight and reach of children.
REFERENCE: Egypt_ Eliquis_ 2.5 mg_ FCT_ LPD (Date of Revision: Feb-22) Egypt
DATE OF THIS DOCUMENT: 22-Sep-22
-Always read the full prescribing information.
-Healthcare professionals should report any suspected adverse reactions to the Egyptian
pharmacovigilance center (EPVC) & pharmacovigilance department of the product
applicant of material.