Eliquis - Drug Monograph

Introduction

Eliquis (apixaban) is an oral anticoagulant medication belonging to the class of direct oral anticoagulants (DOACs). It is a selective inhibitor of factor Xa, a key component in the coagulation cascade. Developed by Bristol-Myers Squibb and Pfizer, Eliquis was approved by the FDA in 2012 and has become a widely prescribed alternative to warfarin for various thromboembolic conditions.

Mechanism of Action

Apixaban directly and reversibly inhibits factor Xa (both free and prothrombinase-bound), which is a critical serine protease in the coagulation cascade. By inhibiting factor Xa, apixaban prevents the conversion of prothrombin to thrombin, thereby reducing thrombus formation. Unlike indirect factor Xa inhibitors, apixaban does not require antithrombin III as a cofactor for its anticoagulant activity.

Indications

• Reduction of risk of stroke and systemic embolism in patients with 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

• For patients with at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL: reduce to 2.5 mg twice daily for atrial fibrillation
• Severe renal impairment (CrCl 15-29 mL/min): use with caution; contraindicated in CrCl <15 mL/min
• No routine dosage adjustment required for hepatic impairment (Child-Pugh A and B)

• Can be taken with or without food
• Do not crush or break tablets
• If a dose is missed, take as soon as possible on the same day and resume twice-daily administration

Pharmacokinetics

• Absorption: Absolute bioavailability approximately 50%; peak concentrations reached 3-4 hours post-dose
• Distribution: Volume of distribution approximately 21 L; 87% protein-bound
• Metabolism: Primarily metabolized via CYP3A4/5; also undergoes sulfation and other oxidative metabolism
• Elimination: Multiple elimination pathways: approximately 25% renal, 55% fecal, and other routes; terminal half-life approximately 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 bleeding which can be serious and potentially fatal
• Spinal/epidural hematoma: Risk with neuraxial anesthesia or spinal puncture; monitor for neurological impairment
• Premature discontinuation: Increased risk of thrombotic events; consider bridging if discontinuation necessary
• Renal impairment: Increased exposure in patients with renal impairment; use caution and adjust dose accordingly
• Hepatic impairment: Avoid use in patients with severe hepatic impairment; increased bleeding risk
• Pregnancy: Use only if potential benefit justifies potential risk to fetus
• Labor and delivery: Safety and effectiveness not established

Drug Interactions

• Ketoconazole, itraconazole, ritonavir: Avoid concomitant use

• Rifampin, carbamazepine, St. John's wort: Avoid concomitant use

• Increased bleeding risk with warfarin, other anticoagulants, aspirin, NSAIDs, and other antiplatelet agents

• Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase bleeding risk

Adverse Effects

• Bleeding events (including major bleeding)
• Nausea
• Anemia
• Contusion
• Rash

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

Monitoring Parameters

• Signs and symptoms of bleeding
• Hemoglobin/hematocrit (if clinically indicated)
• Renal function (serum creatinine at baseline and periodically)
• Liver function tests (periodically)
• Compliance with medication regimen
• Neurological function in patients receiving neuraxial anesthesia

Patient Education

• Take medication exactly as prescribed at the same times each day
• Do not discontinue without consulting healthcare provider
• Immediately report signs of bleeding (unusual bruising, pink or brown urine, red or black stools, coughing up blood, headaches, dizziness, weakness)
• Inform all healthcare providers about Eliquis use before any surgery or dental procedure
• Use soft-bristle toothbrush and electric razor to minimize bleeding risk
• Avoid activities that may increase risk of injury or bleeding
• Report any signs of allergic reactions (rash, itching, swelling)
• Use reliable contraception if of childbearing potential
• Store at room temperature in original container

References

1. Eliquis (apixaban) [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2023. 2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151. 3. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. 4. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol. 2019;74(1):104-132. 5. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021;160(6):e545-e608.