Apixaban - Drug Monograph

Introduction

Apixaban (brand name Eliquis®) is an oral anticoagulant belonging to the class of direct oral anticoagulants (DOACs). It is a selective, reversible inhibitor of factor Xa in the coagulation cascade, offering predictable pharmacokinetics and eliminating the need for routine coagulation monitoring in most patients. Apixaban has revolutionized anticoagulation therapy by providing an effective alternative to vitamin K antagonists with improved safety and convenience profiles.

Mechanism of Action

Apixaban exerts its anticoagulant effect by directly and selectively inhibiting factor Xa (both free and prothrombinase-bound), a key serine protease in the coagulation cascade. By inhibiting factor Xa, apixaban prevents the conversion of prothrombin to thrombin, thereby reducing thrombin generation and ultimately inhibiting fibrin clot formation. This mechanism is independent of antithrombin III, distinguishing it from indirect factor Xa inhibitors like fondaparinux.

Indications

• Stroke and systemic embolism prevention in nonvalvular atrial fibrillation
• Prophylaxis of deep vein thrombosis (DVT) following hip or knee replacement surgery
• Treatment of DVT and pulmonary embolism (PE)
• Reduction in risk of recurrent DVT and PE following initial therapy

Dosage and Administration

• Nonvalvular atrial fibrillation: 5 mg orally twice daily
• DVT/PE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily
• DVT/PE prophylaxis after hip/knee replacement: 2.5 mg twice daily

• Reduce to 2.5 mg twice daily in patients with at least two of the following:

- Serum creatinine ≥1.5 mg/dL - Age ≥80 years - Body weight ≤60 kg

• Can be taken with or without food
• Missed dose: Take as soon as remembered on the same day; do not double the dose

Pharmacokinetics

• Absorption: Bioavailability ~50%; peak concentrations reached 3-4 hours post-dose
• Distribution: Volume of distribution ~21 L; 87% plasma protein bound
• Metabolism: Primarily via CYP3A4/5 with minor contributions from other CYP enzymes; also undergoes direct glucuronidation
• Elimination: Multiple elimination pathways: 25% renal, 55% fecal, remainder metabolized; terminal half-life ~12 hours

Contraindications

• Active pathological bleeding
• Severe hypersensitivity reaction to apixaban
• Patients with prosthetic heart valves (not studied in clinical trials)
• Triple-positive antiphospholipid syndrome (increased thrombotic risk)

Warnings and Precautions

• Bleeding risk: Increased risk of serious and fatal bleeding; risk factors include concomitant antiplatelet therapy, recent surgery, trauma, renal impairment, and elderly patients
• Spinal/epidural hematoma: Risk with neuraxial anesthesia or spinal puncture; monitor for neurological symptoms
• Renal impairment: Increased exposure in severe impairment; use with caution and consider dose reduction
• Hepatic impairment: Avoid use in patients with severe hepatic impairment (Child-Pugh C)
• Discontinuation: Increased risk of thrombotic events with premature discontinuation; consider bridging therapy if necessary

Drug Interactions

• Ketoconazole, itraconazole, ritonavir: Avoid concomitant use

• Rifampin, carbamazepine, phenytoin: Avoid concomitant use

• Increased bleeding risk with warfarin, heparin, aspirin, clopidogrel, NSAIDs

• Diltiazem (moderate CYP3A4 inhibitor): May increase apixaban exposure

Adverse Effects

• Bleeding (including minor bleeding, bruising)
• Nausea
• Anemia

• Major bleeding (gastrointestinal, intracranial)
• Hypersensitivity reactions (including anaphylaxis)
• Spinal/epidural hematoma

Monitoring Parameters

• Signs and symptoms of bleeding
• Renal function (serum creatinine) at baseline and periodically
• Hemoglobin/hematocrit if clinical indication of bleeding
• Liver function tests (baseline)
• Compliance with therapy
• No routine coagulation monitoring required

Patient Education

• Take medication exactly as prescribed at the same times each day
• Do not stop taking without consulting your healthcare provider
• Report any signs of bleeding (unusual bruising, pink/dark urine, bloody stools, coughing up blood)
• Inform all healthcare providers about apixaban use before any procedures
• Use soft-bristle toothbrush and electric razor to minimize bleeding risk
• Report any falls or injuries, especially head trauma
• Avoid activities with high risk of trauma or injury
• Use caution with OTC medications (especially NSAIDs)
• Store at room temperature away from moisture

References

1. Connolly SJ, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-817. 2. Agnelli G, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708. 3. Eliquis® (apixaban) prescribing information. Bristol-Myers Squibb Company; 2021. 4. January CT, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Circulation. 2019;140(2):e125-e151. 5. Stevens SM, et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline. Chest. 2021;160(6):e545-e608.