Apixaban (Eliquis)

Pharmacology of apixaban (Eliquis)
Abdelwahab Ward, BS Pharm, PharmD
ELIQUIS 2.5 MG, 5 MG; ELIMBOSIS; IKSARONT; ARTIXIPAN...
DRUG CLASS ㅡ Direct oral anticoagulants (DOACs).
MECHANISM OF ACTION ㅡ Apixaban is a direct inhibitor of activated factor X (factor Xa).
  • Prophylaxis of recurrent deep-vein thrombosis or pulmonary embolism.
  • Treatment of deep-vein thrombosis and pulmonary embolism.
  • Nonvalvular atrial fibrillation (stroke prevention with CHADS Score 2 or more).
  • Alternative to warfarin (where Pradaxa dyspepsia not tolerated).
  • Poor INR control on warfarin.
  • Important safety information.
      • 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-beta2 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.
  • Atrial fibrillation.
      • Standard dose, Apixaban (Eliquis) 5 mg twice daily.
      • Half-dose indications (2.5 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.
          • Body-weight less than 61 kg, or
          • Serum creatinine 1.5 mg/dL (133 micromol/litre) and over.
  • Venous thromboembolism (VTE).
      • VTE treatment.
          • Initial: 10 mg orally twice daily for 7 days.
          • Maintenance: 5 mg orally twice daily.
          • Prevention of recurrence: 2.5 mg orally twice daily.
  • VTE prophylaxis after surgery.
      • Hip replacement: 2.5 mg orally twice daily for 35 days.
      • Knee replacement: 2.5 mg orally twice daily for 12 days.
  • Active, clinically significant bleeding.
  • Antiphospholipid syndrome (increased risk of recurrent thrombotic events).
  • 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, intracranial hemorrhage.
      • Known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
  • Anesthesia 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); prosthetic heart valve (efficacy not established); risk of bleeding.
  • Cautions.
      • For factor Xa inhibitors, prescription potentially inappropriate (STOPP criteria):
          • With concurrent significant bleeding risk, such as uncontrolled severe hypertension, bleeding diathesis or recent non-trivial spontaneous bleeding (high risk of bleeding).
          • 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 m² (risk of bleeding).
          • Apixaban may be safe in pregnancy.
  • Route: Oral.
  • Peak: 1–2 hours.
  • Duration: Unknown.
  • Metabolism: Hepatic; T1/2: 12 hr.
  • Distribution: Protein binding (87%). It isn't known if drug appears in breast milk.
  • Excretion: Urine (25%).
  • GI: nausea.
  • Hematologic: major bleeding, anemia, bruising.
      • The major adverse effect is bleeding. Therefore, concomitant use of drugs affecting hemostasis including antiplatelets, other anticoagulants, thrombolytic agents, nonsteroidal anti-inflammatory drugs (NSAIDS), SSRIs, and SNRIs should be judicious.
      • Before a patient undergoes elective surgery or an invasive procedure, the drug should be.. 
          • Held for 48 hours if the procedure is a moderate-high risk with clinically significant bleeding. 
          • Held 24 hours if the procedures with a low risk of bleeding
          • Bridging anticoagulation 24 to 48 hours after is not usually recommended. 
          • Apixaban must be restarted following surgical or other procedures once adequate hemostasis is established.

Abdelwahab Ward, BS Pharm, PharmD