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Direct Oral Anticoagulant / AF Pregnancy: Contraindicated — limited human data; animal studies show fetal harm. Use LMWH in pregnancy.

Edoxaban (AF / VTE)

Brand names: Lixiana

Adult dose

Dose: AF stroke prevention: 60 mg once daily (30 mg OD if eGFR 15-50, body weight <=60 kg, or on P-gp inhibitors). VTE treatment: 60 mg OD after >=5-10 days of parenteral anticoagulation.
Route: Oral
Frequency: Once daily
Max: 60 mg/day
Direct factor Xa inhibitor. ENGAGE AF-TIMI 48 trial. Once-daily dosing aids adherence. IMPORTANT: edoxaban efficacy DECREASES at high creatinine clearance (CrCl >95 mL/min) — avoid if CrCl >95 mL/min in AF (paradox: drug is cleared too rapidly, reducing plasma levels).

Paediatric dose

Route: Oral
Seek specialist opinion — not licensed in children

Dose adjustments

Renal

CrCl 15-50: reduce to 30 mg OD. CrCl <15: avoid. Paradox: CrCl >95 mL/min — avoid for AF (reduced efficacy due to rapid clearance — higher stroke rate than warfarin at high CrCl in ENGAGE trial).

Hepatic

Avoid in severe hepatic impairment or hepatic disease with coagulopathy

Clinical pearls

  • ENGAGE AF-TIMI 48 trial (Giugliano et al. NEJM 2013): edoxaban 60 mg OD vs warfarin in AF — non-inferior for stroke/systemic embolism; significant reduction in major bleeding and CV mortality. Established edoxaban as DOAC option for AF.
  • The high-CrCl paradox is unique to edoxaban: patients with CrCl >95 mL/min clear edoxaban too rapidly — plasma levels are subtherapeutic and stroke prevention is inferior to warfarin. This is NOT seen with other DOACs. Check CrCl before prescribing for AF; use alternative DOAC if CrCl >95.
  • 30 mg dose criteria (ANY one = use 30 mg): CrCl 15-50, body weight <=60 kg, or concomitant P-gp inhibitor. Even two criteria apply — still 30 mg (not further reduced).
  • Parenteral lead-in for VTE: unlike rivaroxaban and apixaban (can start orally in VTE), edoxaban and dabigatran require 5-10 days of parenteral anticoagulation (LMWH or UFH) before switching to oral therapy.
  • Andexanet alfa (Ondexxya) reversal: licensed for anti-Xa reversal (rivaroxaban, apixaban, edoxaban) in life-threatening bleeding — high-dose or low-dose regimen depending on last dose and time. Available in specialist centres.

Contraindications

  • CrCl <15 mL/min
  • CrCl >95 mL/min for AF indication (reduced efficacy)
  • Active significant bleeding
  • Mechanical prosthetic heart valves
  • Moderate-severe mitral stenosis
  • Severe hepatic impairment

Side effects

  • Bleeding (GI, intracranial — lower than warfarin for intracranial)
  • Anaemia
  • Rash
  • Elevated LFTs
  • Nausea

Interactions

  • Strong P-gp inhibitors (ketoconazole, cyclosporin, dronedarone) — increase edoxaban levels; use 30 mg OD
  • Strong P-gp inducers (rifampicin, carbamazepine) — reduce levels; avoid
  • Aspirin/NSAIDs — additive bleeding risk

Monitoring

  • CrCl (Cockcroft-Gault) at baseline and annually
  • Signs of bleeding
  • LFTs (baseline)
  • Body weight (dose reduction if <=60 kg)

Reference: BNFc; BNF 90; ENGAGE AF-TIMI 48 Trial (Giugliano et al. NEJM 2013); NICE TA355; SPC Lixiana. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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