Pharm 101: Rivaroxaban

Class

Direct oral anticoagulant (DOAC)

Pharmacodynamics

• Direct factor Xa inhibitor (both free and prothrombinase-bound forms)

Pharmacokinetics

• Bioavailability > 80%
• Rapid onset and rapid offset
• Maximal plasma levels 3 hours post-ingestion
• Small volume of distribution (50L)
• Highly protein bound
• Elimination renal (predominant) and hepatic (CYP3A4)
• Steady state half-life of 5-9 hours is prolonged with renal impairment

Clinical uses

• Prevention of embolic stroke in patients with atrial fibrillation
• Prevention of VTE following hip/knee surgery
• Treatment of VTE
• Offers advantages over warfarin:
  • More rapid onset/offset of action
  • More predictable effect, wider therapeutic index
  • INR monitoring not required
  • Fewer drug and dietary interactions

Adverse effects

• Bleeding
• Reversal is less straight forward than warfarin:
  • Andexanet alfa is a factor Xa “decoy” molecule without procoagulant activity that competes for binding to anti-Xa drugs and rapidly decreases anti-Xa effect

Precautions/contraindications

• Dose adjustment in renal failure
• Contraindicated in dialysis patients

Further Reading

• Nickson C. Rivaroxaban and bleeding
• Long N. Toxicology Library: NOACS