Direct Factor Xa Inhibitors

Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Pharmacokinetics of direct oral anticoagulant
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

Introduction

In the 1980s, natural inhibitors like antistasin and tick anticoagulant peptide confirmed factor Xa as a drug target. In the 1990s, synthetic inhibitors such as DX-9065a were developed but had poor oral absorption. Bayer’s work in the late 1990s led to rivaroxaban, the first oral direct factor Xa inhibitor approved in 2008. Following rivaroxaban, apixaban, edoxaban, and betrixaban were approved between 2011 and 2017. These drugs transformed anticoagulation by offering effective, orally available alternatives for preventing and treating blood clots and stroke in atrial fibrillation.

Mechanism of action

Examples of medication brand names

Savaysa(edoxaban)

Xanoxiban(rivaroxaban)

Orgoroxaban(rivaroxaban)

Eliquis(apixaban)

Arixtra(fondaparinux)

Lixiana(edoxaban)

BetriXa(betrixaban)

Bevyxxa(betrixaban)

Pharmacokinetics of direct oral anticoagulant

Transport proteins and metabolic elimination pathway of Direct Oral Anticoagulant

Indication

Direct factor Xa inhibitors are primarily indicated for: Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). Treatment and secondary prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). Prophylaxis of VTE following major orthopedic surgeries such as knee or hip replacement. These agents serve as effective alternatives to warfarin, especially when routine monitoring is challenging or drug interactions are a concern.

Side Effects

Precautions

Contraindications

Avoid use in patients with active bleeding or high bleeding risk.
Do not stop treatment prematurely without alternative anticoagulation due to increased risk of ischemic events.
Use caution in patients with renal or hepatic impairment; dose adjustments or alternative anticoagulants may be needed.
Avoid combining with other drugs that increase bleeding risk (e.g., NSAIDs, antiplatelets).
Inform healthcare providers before surgery, especially spinal/epidural procedures, due to risk of hematoma.
Monitor for signs of bleeding (nosebleeds, GI bleeding, bruising).
Not recommended in pregnancy or breastfeeding due to unknown fetal/neonatal effects.
Use with caution in patients with history of GI bleeding or bleeding disorders.

Active pathological bleeding.
Severe hepatic disease with coagulopathy (Child-Pugh Class C).
Mechanical heart valves and rheumatic mitral stenosis.
Severe renal impairment (e.g., CrCl <15-25 mL/min depending on the drug).
Hypersensitivity to the drug or excipients.
Pregnancy and breastfeeding.
Undergoing neuraxial anesthesia or spinal puncture (risk of spinal/epidural hematoma).
Triple positive antiphospholipid syndrome.
Significant inherited or acquired bleeding disorders.