Apixaban

Generic Name

Apixaban

Mechanism

• Selective inhibition of activated Factor Xa → prevents conversion of prothrombin to thrombin.
• Binds both free Factor Xa and clot‑bound Factor Xa, ensuring *sustained anticoagulation* during clot formation.
• Does not inhibit thrombin (Factor IIa) or other coagulation factors, giving a predictable, fixed‑dose effect with minimal *anticoagulant–antibody* interaction.

Pharmacokinetics

• Absorption: Bioavailability ~50 %; peak plasma at 3–4 h.
• Distribution: ~50 % protein‑bound (mostly to albumin).
• Metabolism: Primarily CYP3A4/5; minor CYP2J2.
• Elimination: ~25 % renal (urine), ~60 % fecal; half‑life 12 h in adults.
• Drug interactions: Strong CYP3A4, P‑gp inhibitors/inducers alter exposure.

Indications

• Atrial fibrillation: Stroke & systemic embolism prevention (2 mg BID).
• Venous thromboembolism (VTE):
• Acute treatment (short‑course) (2 mg BID).
• Extended/maintenance phase (2 mg BID).
• Prophylaxis after hip/knee arthroplasty (2 mg BID for 10–14 days).

Contraindications

• Contraindicated:
• Concomitant full‑dose anticoagulants.
• Severe hepatic impairment (Child‑Pugh C).
• Active bleeding or high bleed risk.
• Warnings:
• Major bleeding → monitor promptly.
• Renal/hepatic dysfunction → dose adjustment.
• Pregnancy: Category C; avoid if possible.

Dosing

• Standard adult dosing:
• 2 mg orally, twice daily, on an empty stomach.
• Renal adjustment:
• CrCl 15–29 mL/min: 2 mg BID for VTE/AF; 2 mg/once daily for prophylaxis.
• CrCl <15 mL/min: Consider alternative therapy.
• Administration tips:
• Swallow capsules whole; avoid crushing.
• Consistent timing relative to meals may improve absorption.

Adverse Effects

• Common
• Epistaxis, gum bleeding, bruising, gastrointestinal discomfort.
• Serious
• Internal bleeding (GI, intracranial).
• Hemorrhagic stroke >5% risk during therapeutic dosing.
• Thrombotic events if drug discontinued abruptly.

Monitoring

• Routine coagulation tests (PT/INR, aPTT) not required.
• Renal: CrCl every 3–6 months or sooner if symptoms appear.
• Hepatic: LFTs if liver disease risk.
• Platelets: Monitor if unexplained thrombocytopenia develops.

Clinical Pearls

• Bleeding reversal: Idarucizumab is specific for dabigatran; *andexanet alfa* is the current antidote for Factor Xa inhibitors (including apixaban) but use only in severe bleeding or urgent surgery.
• Peri‑operative management: Stop apixaban 24 h before high‑bleed‑risk surgery; resume 48 h post‑op if hemostasis achieved.
• Drug interactions coding: Use *CYP3A4*/P‑gp inhibitor combo (e.g., ketoconazole + ritonavir) → ~4–6× increase; may halve dose or pause.
• Patient education: Emphasize consistent dosing schedule; missing >24 h may warrant restart at full dose once resumed.
• Special populations: In elderly (>75 yr), consider lower risk of subsequent atrial fibrillation stroke; anticoagulation benefits outweigh bleeding risk with proper monitoring.

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• References: AHA/ACC (2023) guidelines for atrial fibrillation; FDA prescribing information; *UpToDate* 2025 review on DOACs.