Formulary
Apixaban: Indications, Dosing, Side Effects and Interactions
Apixaban is a direct inhibitor of activated factor X (factor Xa).
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Apixaban: Indications, Dosing, Side Effects and Interactions
Apixaban is a direct inhibitor of activated factor X (factor Xa).
Drug action
Apixaban is a direct inhibitor of activated factor X (factor Xa).
Indications and dose
**Prophylaxis of venous thromboembolism following knee replacement surgery**
- **Adult** (By Mouth): 2.5 mg twice daily for 10-14 days, to be started 12-24 hours after surgery.
**Prophylaxis of venous thromboembolism following hip replacement surgery**
- **Adult** (By Mouth): 2.5 mg twice daily for 32-38 days, to be started 12-24 hours after surgery.
**Treatment of deep-vein thrombosis,Treatment of pulmonary embolism**
- **Adult** (By Mouth): Initially 10 mg twice daily for 7 days, then maintenance 5 mg twice daily.
**Prophylaxis of recurrent deep-vein thrombosis,Prophylaxis of recurrent pulmonary embolism**
- **Adult** (By Mouth): 2.5 mg twice daily, following completion of 6 months anticoagulant treatment.
**Prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation and at least one risk factor [such as previous stroke or transient ischaemic attack, symptomatic heart failure, diabetes mellitus, hypertension, or age 75 years and over]**
- **Adult** (By Mouth): 5 mg twice daily, reduce dose to 2.5 mg twice daily in patients with at least two of the following characteristics: age 80 years and over, weight 60 kg or less, or serum-creatinine 133 micromol/litre and over.
Cautions
Anaesthesia with postoperative indwelling epidural catheter (risk of paralysis-monitor neurological signs and wait 20-30 hours after apixaban dose before removing catheter and do not give next dose until at least 5 hours after catheter removal); elderly; low body-weight; risk of bleeding Cautions, further information Elderly For factor Xa inhibitors, Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria to aid medication reviews (see Prescribing in the elderly for information). Potentially inappropriate: with concurrent significant bleeding risk, such as uncontrolled severe hypertension, bleeding diathesis or recent non-trivial spontaneous bleeding (high risk of bleeding) for first deep venous thrombosis without continuing provoking risk factors (e.g. thrombophilia) for greater than 6 months (no proven added benefit) for first pulmonary embolus without continuing provoking risk factors for greater than 12 months (no proven added benefit) as part of dual therapy with an antiplatelet agent in patients with stable coronary, cerebrovascular or peripheral arterial disease, without a clear indication for anticoagulant therapy (no added benefit) if eGFR less than 15 mL/min/1.73 m (contra-indicated in kidney failure; risk of bleeding)
Contraindications
Active, clinically significant bleeding; antiphospholipid syndrome (increased risk of recurrent thrombotic events); prosthetic heart valve (efficacy not established); significant risk of major bleeding; use with any other anticoagulant Contra-indications, further information Significant risk of major bleeding Avoid in conditions with significant risk factors for major bleeding, including current or recent gastrointestinal ulceration, 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. M Use with any other anticoagulant Concomitant use with any other anticoagulant is contra-indicated, except when switching therapy, or when heparin is given at doses necessary to maintain an open central venous or arterial catheter or for catheter ablation-use with caution. M
Side effects
Common or very common Anaemia; haemorrhage; nausea; skin reactions Uncommon CNS haemorrhage; hypotension; post procedural haematoma; thrombocytopenia; wound complications
Interactions
**Severe interactions:**
- Other concomitant therapies No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when apixaban was coadministered with atenolol or famotidine.
- Effect of apixaban on other medicinal products In vitro apixaban studies showed no inhibitory effect on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50 > 45 M) and...
- Apixaban is not a significant inhibitor of P-gp.
**Other interactions (33):**
- Inhibitors of CYP3A4 and P-gp Coadministration 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...
- The use of apixaban 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,...
- Active substances which are not considered strong inhibitors of both CYP3A4 and P-gp, (e.g., amiodarone, clarithromycin, diltiazem, fluconazole, naproxen, quinidine, verapamil) are expected to...
- No dose adjustment for apixaban is required when coadministered with agents that are not strong inhibitors of both CYP3A4 and P-gp.
- For example, diltiazem (360 mg once a day), considered a moderate CYP3A4 and a weak P-gp inhibitor, led to a 1.4-fold increase in mean apixaban AUC and a 1.3-fold increase in C max .
- Naproxen (500 mg, single dose) an inhibitor of P-gp but not an inhibitor of CYP3A4, led to a 1.5-fold and 1.6-fold increase in mean apixaban AUC and C max , respectively.
Pregnancy
Manufacturer advises avoid-no information available.
Breast feeding
Manufacturer advises avoid-present in milk in animal studies.
Hepatic impairment
Manufacturer advises caution in mild to moderate impairment (or if hepatic transaminases greater than 2 times the upper limit of normal, or if bilirubin is equal or greater than 1.5 times the upper limit of normal); avoid in severe impairment or impairment associated with coagulopathy and clinically relevant bleeding risk.
Renal impairment
Important safety information For apixaban MHRA/CHM advice: New oral anticoagulants apixaban ( Eliquis ), dabigatran ( Pradaxa ) and rivaroxaban ( Xarelto ) (October 2013) The following contra-indications now apply to all new oral anticoagulants, for all indications and doses: a lesion or condition, if considered a significant risk factor for major bleeding-see Contra-indications for further information; concomitant treatment with any other anticoagulant agent-see Contra-indications for further information. Healthcare professionals are advised to take caution when deciding to prescribe these anticoagulants to patients with other conditions, undergoing other procedures, and on other treatments, which may increase the risk of major bleeding. The renal function of patients should also be considered. MHRA/CHM advice: Direct-acting oral anticoagulants (DOACs): increased risk of recurrent thrombotic events in patients with antiphospholipid syndrome (June 2019) A clinical trial has shown an increased risk of recurrent thrombotic events associated with rivaroxaban compared with warfarin, in patients with antiphospholipid syndrome and a history of thrombosis. There may be a similar risk associated with other DOACs. Healthcare professionals are advised that DOACs are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients who test positive for all three antiphospholipid tests-lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies. Continued treatment should be reviewed in these patients to determine if appropriate, and switching to a vitamin K antagonist such as warfarin should be considered. MHRA/CHM advice: Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents (June 2020) The MHRA reminds healthcare professionals to remain vigilant for signs and symptoms of bleeding complications during treatment with apixaban after ongoing reports of serious, potentially fatal bleeds associated with the use of DOACs. Healthcare professionals are also advised to use apixaban with caution in patients with increased bleeding risk, and to ensure that those with renal impairment are dosed appropriately and their renal function monitored during treatment. Patients should be counselled on the signs and symptoms of bleeding, and encouraged to read the patient information leaflet. The apixaban reversal agent andexanet alfa ( Ondexxya ) is available if required; its reversal effects should be monitored using clinical parameters, as anti-FXa assay results may not be reliable. MHRA/CHM advice: Warfarin and other anticoagulants: monitoring of patients during the COVID-19 pandemic (October 2020) Healthcare professionals are reminded that: direct-acting oral anticoagulants (DOACs), such as apixaban, may interact with other medicines (including antibacterials and antivirals)-advice in product literature should be followed to minimise the risk of potential interactions; if patients are switched from warfarin to apixaban, warfarin treatment should be stopped before apixaban treatment is started to reduce the risk of over-anticoagulation and bleeding. MHRA/CHM advice: Direct-acting oral anticoagulants (DOACs): reminder of dose adjustments in patients with renal impairment (May 2023) Healthcare professionals are reminded that: exposure to DOACs, such as apixaban, is increased in patients with renal impairment, and these patients should receive an appropriately adjusted dose-see Renal impairment for further information; such patients should be reviewed regularly during treatment to ensure the dose remains appropriate; renal function should be assessed by calculating creatinine clearance using the Cockcroft and Gault formula.
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Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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