Direct Factor Xa Inhibitor (DOAC) Pregnancy: Avoid — use LMWH in pregnancy (DOACs contraindicated).

Edoxaban (VTE Treatment/PE — Vascular)

Brand names: Lixiana

Adult dose

Dose: VTE/PE treatment: 60 mg once daily (after ≥5 days LMWH; 'LMWH lead-in' mandatory). Dose reduce to 30 mg once daily if: weight ≤60 kg, eGFR 15–50 mL/min, or concomitant P-gp inhibitor

Route: Oral

Frequency: Once daily

Max: 60 mg/day

Unique feature among DOACs: REQUIRES 5-day parenteral lead-in with LMWH or UFH before switching to edoxaban (based on HOKUSAI trial design). This differs from rivaroxaban/apixaban which can start orally immediately. Once-daily dosing advantage for long-term VTE/CAD prevention. LMWH lead-in prevents early prothrombotic effect.

Paediatric dose

Route:

Not licensed for VTE in children. MHRA licensed indication in UK: adults only.

Dose adjustments

Renal

eGFR 15–50 mL/min: 30 mg once daily. eGFR <15: avoid.

Hepatic

Moderate-severe hepatic impairment: avoid.

Clinical pearls

HOKUSAI-VTE trial (Büller et al. NEJM 2013): edoxaban vs warfarin in VTE (after heparin lead-in) — non-inferior for primary efficacy (recurrent VTE) with significantly less major or clinically relevant bleeding (8.5% vs 10.3%). Subgroup with severe PE showed particular benefit
LMWH lead-in is mandatory: the HOKUSAI trial mandated ≥5 days of heparin before edoxaban — this bridges the gap before full anticoagulant effect is established and avoids early thrombotic risk. Prescribers must ensure this step is not omitted
Severe PE special consideration: edoxaban showed greatest benefit in patients with moderate-severe PE (elevated troponin or RV dysfunction on echo) — an important subgroup where anticoagulant selection may affect outcome

Contraindications

eGFR <15 mL/min
Active bleeding
Antiphospholipid syndrome
Prosthetic valves

Side effects

Bleeding (major: 1.4% vs 1.6% for warfarin in HOKUSAI — non-inferior; less ICH)
Anaemia
Abnormal LFTs
Nausea

Interactions

P-gp inhibitors (verapamil, quinidine, dronedarone, erythromycin — reduce edoxaban to 30 mg/day)
P-gp inducers (rifampicin, phenytoin — reduce edoxaban efficacy significantly; avoid)
Aspirin and NSAIDs (additive bleeding)

Monitoring

eGFR at baseline and annually
Body weight (dose reduction criterion ≤60 kg)
Bleeding signs
LFTs (baseline)
Drug interactions at medication reconciliation

Reference: BNFc; BNF 90; HOKUSAI-VTE Trial (Büller et al. NEJM 2013); NICE NG185 (VTE); ESC PE Guidelines 2019; MHRA SPC Lixiana. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Edoxaban (AF Stroke Prevention / VTE) · Direct Factor Xa Inhibitor (DOAC)

Pathways