Schedule H1

Oral

• Tablets: 15 mg, 30 mg, 60 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Nonvalvular Atrial Fibrillation (NVAF) – Stroke Prevention

Parameter Recommendation

Starting dose 60 mg once daily

Titration Not applicable

Usual maintenance dose 60 mg once daily

Maximum dose 60 mg once daily

Dose reduction to 30 mg once daily required if:

• eGFR 15–50 mL/min

• Body weight ≤60 kg

• Concomitant use with potent P-glycoprotein inhibitors

Key clinical notes:

• Avoid in patients with eGFR >95 mL/min (reduced efficacy observed in ENGAGE AF-TIMI 48 trial)

• Contraindicated with mechanical heart valves or moderate-to-severe mitral stenosis

1. Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Parameter Recommendation

Starting dose 60 mg once daily (after 5–10 days of parenteral anticoagulant)

Titration Not applicable

Usual maintenance dose 60 mg once daily

Maximum dose 60 mg once daily

Dose reduction to 30 mg once daily required if:

• Body weight ≤60 kg

• CrCl 15–50 mL/min

• Concomitant potent P-gp inhibitor use

Treatment duration:

• Minimum 3 months

• Extend based on ongoing risk factors and bleeding assessment

Key clinical note: Parenteral anticoagulant lead-in (LMWH or UFH for 5–10 days) is mandatory before starting edoxaban for VTE treatment.

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Notes

Postoperative VTE prophylaxis (orthopaedic surgery) 30 mg once daily 10–14 days (knee replacement); up to 35 days (hip replacement) OFF-LABEL; Specialist only; Evidence: International RCTs (STARS E-3, STARS J-V); Not approved by CDSCO

PAEDIATRIC DOSING (Specialist Only)

NOT APPROVED BELOW 18 YEARS

Primary Indications (Approved / Standard in India)

Not applicable — No approved paediatric indications in India.

Secondary Indications – Paediatric Doses (Off-label)

Indication Age Dose Duration Notes

Treatment of paediatric VTE ≥12 years 1–2 mg/kg once daily (maximum 60 mg/day) As per clinical requirement OFF-LABEL; Specialist paediatric haematology only; Evidence: Extrapolated from adult pharmacokinetics and limited international trial data

Safety monitoring:

• Baseline and periodic renal function assessment

• Clinical monitoring for bleeding signs

• Anti-Xa activity monitoring where available

• CBC monitoring

Minimum age limit: 12 years (use only if no alternative DOAC is available)

95 Avoid for NVAF indication (potential reduced efficacy); consider alternative DOAC

50–95 60 mg once daily

15–50 30 mg once daily

<15 or on dialysis Not recommended (insufficient data)

Additional notes:

• For DVT/PE with CrCl 15–50 mL/min: reduce to 30 mg once daily

• Avoid in ESRD and patients on haemodialysis

Impairment Level Recommendation

Mild (Child-Pugh A) No dose adjustment required

Moderate (Child-Pugh B) Use with caution; no dose adjustment but monitor for bleeding

Severe (Child-Pugh C) Contraindicated

• Active clinically significant bleeding

• Severe hepatic impairment (Child-Pugh C) or hepatic disease with coagulopathy

• Mechanical prosthetic heart valves

• Moderate to severe mitral stenosis (rheumatic origin)

• Concomitant use with other anticoagulants (except during switching period)

• Known hypersensitivity to edoxaban or any excipient

• Lesions at increased risk of clinically significant bleeding (e.g., recent cerebral haemorrhage, oesophageal varices)

• Body weight ≤60 kg (increased drug exposure)

• eGFR 15–30 mL/min (limited clinical data)

• Concomitant use with antiplatelet agents (increased bleeding risk)

• Recent major surgery, trauma, or gastrointestinal bleeding

• Uncontrolled severe hypertension

• Conditions predisposing to bleeding (active peptic ulcer disease, recent brain/spinal surgery, vascular retinopathy)

• Concomitant P-gp inducers (potential reduced efficacy)

Parameter Recommendation

Safety status CONTRAINDICATED

Risk Crosses placenta; risk of fetal haemorrhage

Preferred alternatives LMWH (enoxaparin, dalteparin) throughout pregnancy

When it may be used Avoid; only under specialist haematology input if absolutely no alternative exists

Monitoring Not applicable — avoid use

Parameter Recommendation

Compatibility Not recommended during breastfeeding

Expected milk levels Unknown; likely low based on molecular weight

Preferred alternatives LMWH or warfarin (if INR stable postpartum)

Infant monitoring Avoid breastfeeding if edoxaban essential; if unavoidable, monitor infant for bruising or bleeding signs

Parameter Recommendation

Starting dose 30–60 mg once daily based on renal function and body weight

Titration Cautious approach; no specific titration required

Extra risks Falls, accumulation with declining renal function, polypharmacy interactions

Special considerations Lower threshold for 30 mg dose in frail elderly; frequent renal function monitoring recommended

Other anticoagulants (warfarin, heparin, other DOACs) Additive bleeding risk Avoid concomitant use (except during switching)

Ciclosporin (potent P-gp inhibitor) Increases edoxaban exposure by ~70% Reduce dose to 30 mg once daily

Dronedarone (potent P-gp inhibitor) Increases edoxaban exposure Reduce dose to 30 mg once daily

Ketoconazole (systemic) Increases edoxaban levels Reduce dose to 30 mg once daily

Rifampicin (potent P-gp inducer) Decreases edoxaban levels significantly Avoid concomitant use (risk of thrombosis)

Erythromycin Increases edoxaban exposure Reduce dose to 30 mg once daily

Drug/Class Effect Management

Clarithromycin Mild increase in edoxaban exposure Monitor for bleeding; no routine dose change

Amiodarone Mild increase in AUC (~40%) Monitor for bleeding

NSAIDs Increased gastrointestinal bleeding risk Use with caution; avoid prolonged use

Aspirin/Clopidogrel Additive bleeding risk Use cautiously with clinical justification; monitor closely

SSRIs/SNRIs Impaired platelet function Monitor for bleeding

Carbamazepine, Phenytoin May reduce edoxaban exposure Assess risk-benefit; consider alternative anticonvulsant

Verapamil Mild increase in edoxaban levels Monitor; no routine dose adjustment

• Bleeding (cutaneous, epistaxis, vaginal, gingival)

• Anaemia

• Rash and pruritus

• Nausea

• Elevated hepatic transaminases

• Abdominal pain

Adverse Effect Action Required

Major bleeding (intracranial, gastrointestinal, retroperitoneal) Immediate discontinuation; supportive care; consider andexanet alfa or PCC if available

Severe hepatotoxicity Discontinue; monitor LFTs; specialist referral

Thrombocytopenia Investigate cause; consider discontinuation

Anaphylaxis/angioedema Immediate discontinuation; emergency management

After initiation Clinical assessment for bleeding; recheck renal function at 1–2 weeks

Long-term Renal function every 3–6 months (more frequently if elderly, CKD, or intercurrent illness); periodic CBC and LFTs

Note: Routine INR/PT monitoring not required. Anti-Xa assay (edoxaban-calibrated) may be used in specific situations (overdose, urgent surgery, bleeding).

• Lixiana® (Daiichi Sankyo / Mankind Pharma)

• Edoxa® (Dr Reddy's Laboratories)

• Lupiedoxa® (Lupin)

• Edastar™ (USV)

• Edofast® (Glenmark)

• Under NLEM 2022: No

• NPPA price control: No

• Government supply: Available at select tertiary care centres

• Mandatory parenteral lead-in: Always initiate parenteral anticoagulation (LMWH/UFH) for 5–10 days before switching to edoxaban for DVT/PE treatment.

• High eGFR caution: Avoid edoxaban for stroke prevention in NVAF if CrCl >95 mL/min — increased stroke risk observed; prefer alternative DOACs.

• Not interchangeable: Edoxaban doses are not equivalent to apixaban or rivaroxaban; each DOAC has distinct pharmacokinetics.

• Weight-based adjustment: Consider 30 mg dose even with normal renal function if body weight ≤60 kg.

• Reversal: Andexanet alfa is the specific reversal agent; 4-factor PCC may be used if unavailable.

• No routine coagulation monitoring: Unlike warfarin, regular INR monitoring is not needed.

edoxaban; DOAC; factor Xa inhibitor; atrial fibrillation; DVT; pulmonary embolism; anticoagulant; renal-dose-adjustment; elderly-caution; pregnancy-contraindicated; breastfeeding-avoid

RxIndia v1.1 — 28 May 2025

• CDSCO Drug Approval Documents

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine, 11th Edition

• AIIMS Anticoagulation Guidelines

• ICMR Guidelines on Atrial Fibrillation and VTE Management (2022)

• Edoxaban Product Insert – Lixiana® (Daiichi Sankyo)

• ENGAGE AF-TIMI 48 Trial (off-label insight for eGFR >95 caution)

• Hokusai-VTE Trial (off-label insight for VTE duration)