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  • Eliquis
    / Pfizer


    Active Ingredient
    Apixaban 2.5 mg, 5 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    60 X 2.5 mg

    partial basket chart 77578 5562

    Film Coated Tablets

    60 X 5 mg

    partial basket chart 77583 5563

    Related information


    Dosage

    Prevention of VTE (VTEp): elective hip or knee replacement surgery: The recommended dose of Apixaban 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.
    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.
    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.
    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, immobilisation). 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. See prescribing information for full details.
    The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding.
    Missed dose: If a dose is missed, the patient should take Apixaban immediately and then continue with twice daily intake as before.
    Switching: Switching treatment from parenteral anticoagulants to Apixaban (and vice versa) can be done at the next scheduled dose. These agents 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, discontinue warfarin or other VKA therapy and start Apixaban when the international normalised ratio (INR) is < 2.0.
    Switching from Apixaban to VKA therapy: When converting patients from Apixaban to VKA therapy, continue administration of Apixaban for at least 2 days after beginning VKA therapy. After 2 days of coadministration of Apixaban with VKA therapy, obtain an INR prior to the next scheduled dose of Apixaban. Continue coadministration of Apixaban and VKA therapy until the INR is ≥ 2.0.
    Switching between Apixaban and anticoagulants other than warfarin: Discontinue one being taken and begin the other at the next scheduled dose.
    Renal impairment:
    In patients with mild or moderate renal impairment, the following recommendations apply:
    – for the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), no dose adjustment is necessary.
    – for the prevention of stroke and systemic embolism in patients with NVAF and serum creatinine ≥ 1.5 mg/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 the prevention of VTE in elective hip or knee replacement surgery (VTEp).
    -for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt) apixaban is to be used with caution;
    -for the prevention of stroke and systemic embolism in patients with 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, there is no clinical experience therefore apixaban is not recommended.
    Hepatic impairment: Apixaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. 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). No dose adjustment is required in patients with mild or moderate hepatic impairment. Patients with elevated liver enzymes alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) >2 x ULN or total bilirubin ≥1.5 x ULN were excluded in clinical trials. Therefore Apixaban should be used with caution in this population. Prior to initiating Apixaban, liver function testing should be performed.
    Body weight: VTEp and VTEt – No dose adjustment required.
    NVAF – No dose adjustment required, unless criteria for dose reduction are met.
    Gender: No dose adjustment required.
    Elderly: VTEp and VTEt – No dose adjustment required.
    NVAF – No dose adjustment required, unless criteria for dose reduction are met.
    Cardioversion (NVAF): Patients can stay on apixaban while being cardioverted.
    Paediatric population: The safety and efficacy of ELIQUIS in children and adolescents below age 18 have not been established. No data are available.
    Method of administration: Oral use. ELIQUIS should be swallowed with water, with or without food. For patients who are unable to swallow whole tablets, Eliquis tablets may be crushed and suspended in water, or 5% dextrose in water (D5W), or apple juice or mixed with apple puree and immediately administered orally. Alternatively, Eliquis tablets may be crushed and suspended in 60 mL of water or D5W and immediately delivered through a nasogastric tube.
    Crushed Eliquis tablets are stable in water, D5W, apple juice, and apple puree for up to 4 hours.


    Indications

    2.5 mg film-coated tablets: Prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery.
    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 ischaemic attack (TIA); age ≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II).
    Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.
    5 mg film-coated tablets: 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 ischaemic attack (TIA); age ≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II).
    Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults.


    Contra-Indications

    – 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. 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.
    – Concomitant treatment with any other anticoagulant agent e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, rivaroxaban, dabigatran, etc.) except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter.


    Special Precautions

    Haemorrhage risk: As with other anticoagulants, patients taking ELIQUIS are to be carefully observed for signs of bleeding. It is recommended to be used with caution in conditions with increased risk of haemorrhage. ELIQUIS administration should be discontinued if severe haemorrhage occurs. Although treatment with apixaban does not require routine monitoring of exposure, a calibrated quantitative anti-Factor Xa assay may be useful in exceptional situations where knowledge of apixaban exposure may help to inform clinical decisions, e.g., overdose and emergency surgery.
    Interaction with other medicinal products affecting haemostasis: Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated.
    The concomitant use of ELIQUIS 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 drugs (NSAIDs), including acetylsalicylic acid.
    Following surgery, other platelet aggregation inhibitors are not recommended concomitantly with ELIQUIS.
    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 ELIQUIS. See prescribing information for full details.
    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: Safety and efficacy of Eliquis have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of Eliquis 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: ELIQUIS 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.
    Eliquis 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.
    Eliquis should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established.
    See prescribing information for full details.


    Side Effects

    Common adverse reactions were haemorrhage, contusion, epistaxis, and haematoma.
    See prescribing information for full details.


    Drug interactions

    Inhibitors of CYP3A4 and P-gp: Co-administration of apixaban with ketoconazole (400 mg once a day), a strong inhibitor of both CYP3A4 and P-gp, led to a 2-fold increase in mean apixaban AUC and a 1.6-fold increase in mean apixaban Cmax.
    The use of ELIQUIS is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp, such as azole-antimycotics (e.g., ketoconazole, itraconazole, voriconazole and posaconazole) and HIV protease inhibitors (e.g., ritonavir).
    Inducers of CYP3A4 and P-gp: Co-administration of apixaban with rifampicin, a strong inducer of both CYP3A4 and P-gp, led to an approximate 54% and 42% decrease in mean apixaban AUC and Cmax, respectively. The concomitant use of apixaban with other strong CYP3A4 and P-gp inducers (e.g., phenytoin, carbamazepine, phenobarbital or St. John’s Wort) may also lead to reduced apixaban plasma concentrations. No dose adjustment for apixaban is required during concomitant therapy with such agents, however in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp apixaban should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke and systemic embolism in patients with NVAF and for the prevention of recurrent DVT and PE.
    Apixaban is not recommended for the treatment of DVT and PE in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp since efficacy may be compromised.
    Anticoagulants,platelet aggregation inhibitors, SSRIs/SNRIs and NSAIDs: Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There are no data from the use of apixaban in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Apixaban is not recommended during pregnancy.
    Breast-feeding: It is unknown whether apixaban or its metabolites are excreted in human milk. Available data in animals have shown excretion of apixaban in milk. In rat milk, a high milk to maternal plasma ratio (Cmax about 8, AUC about 30) was found, possibly due to active transport into the milk. A risk to newborns and infants cannot be excluded. A decision must be made to either discontinue breast-feeding or to discontinue/abstain from apixaban therapy.


    Overdose

    There is no antidote to Apixaban. Overdose of apixaban may result in a higher risk of bleeding. In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. The initiation of appropriate treatment, e.g., surgical haemostasis or the transfusion of fresh frozen plasma should be considered.
    See prescribing information for full details.


    Important notes

    Storage: Store below 30°C.
    Lactose: contains lactose.


    Manufacturer
    Bristol-Myers Squibb, Italy
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