Schedule H

Oral

• Tablets: 1 mg, 2 mg, 3 mg, 5 mg

• Note: Not all strengths uniformly available across all pharmacies; 2.5 mg tablets available from select manufacturers

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Venous Thromboembolism (VTE) — Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Parameter Recommendation

Starting dose 5 mg once daily for first 2 days; use 2–3 mg in elderly, hepatic impairment, malnutrition, or high bleeding risk

Overlap therapy Initiate concurrently with LMWH/UFH; overlap for minimum 5 days AND until INR ≥2.0 for at least 24 hours

Titration Adjust based on INR response; target INR 2.0–3.0

Usual maintenance dose 2–10 mg once daily (highly variable; INR-guided)

Maximum dose No fixed maximum; dose determined by INR target

Duration of Therapy:

Scenario Duration

First VTE provoked by transient risk factor 3 months

First unprovoked VTE 3–6 months minimum; consider extended therapy

Recurrent unprovoked VTE Indefinite (lifelong) with annual bleeding risk reassessment

VTE with active malignancy LMWH preferred; warfarin if LMWH not feasible — continue while cancer active

1. Atrial Fibrillation (Valvular and Non-valvular)

Parameter Recommendation

Starting dose 3–5 mg once daily; 2–3 mg in elderly or high-risk patients

Titration Based on INR; check INR on day 3–5, then adjust

Target INR 2.0–3.0 for most patients

Usual maintenance dose INR-guided (typically 2–7 mg/day)

Maximum dose Not applicable — INR-guided

Clinical Notes:

• Use CHA₂DS₂-VASc score to determine need for anticoagulation

• Use HAS-BLED score for bleeding risk assessment annually

• Long-term/lifelong therapy in most cases

• Non-valvular AF: DOACs may be considered as alternative where appropriate

1. Mechanical Prosthetic Heart Valves

Valve Position Target INR Additional Notes

Aortic valve (bileaflet/tilting disc, no risk factors) 2.0–3.0 Lower intensity acceptable in low-risk cases

Aortic valve with risk factors (AF, LV dysfunction, prior thromboembolism) 2.5–3.5 Add low-dose aspirin (75–100 mg) in high-risk

Mitral valve (any type) 2.5–3.5 Higher thrombogenic potential

Multiple valves or older generation valves 2.5–3.5 Consult cardiology

Parameter Recommendation

Starting dose 3–5 mg once daily

Titration INR-guided; check frequently until stable

Usual maintenance dose Individualised; typically 3–8 mg/day

Duration Lifelong

Clinical Notes:

• LMWH bridging required perioperatively

• DOACs are contraindicated in mechanical valves

• Regular dental prophylaxis advised

1. Rheumatic Mitral Valve Disease with Atrial Fibrillation

Parameter Recommendation

Starting dose 3–5 mg once daily

Titration INR-guided

Target INR 2.0–3.0

Usual maintenance dose INR-guided

Duration Long-term/lifelong

Clinical Notes:

• Classified as valvular AF; DOACs not recommended

• Warfarin remains standard of care in India for rheumatic valvular disease

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Antiphospholipid Syndrome (APS) with thrombosis Target INR 2.0–3.0 (standard); INR 3.0–4.0 in recurrent arterial events (controversial) Lifelong OFF-LABEL — Specialist only; evidence from international guidelines and Indian rheumatology practice

Cardioembolic Stroke (secondary prevention) Target INR 2.0–3.0 Long-term based on aetiology OFF-LABEL — Initiate 4–14 days post-stroke depending on infarct size and haemorrhagic transformation risk; specialist decision

Left Ventricular Thrombus post-MI Target INR 2.0–3.0 3–6 months or until thrombus resolution on imaging OFF-LABEL — Used in Indian cardiology practice; echocardiographic follow-up required

Dilated Cardiomyopathy with severe LV dysfunction and AF/thrombus Target INR 2.0–3.0 Long-term OFF-LABEL — Specialist only

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Approved uses: Mechanical prosthetic heart valves, VTE treatment/prophylaxis, Fontan circulation, cardiac shunts, Kawasaki disease with coronary aneurysms

Neonates (<1 month) 0.2 mg/kg once daily Adjust based on INR; check day 2–3 Indication-dependent INR every 1–2 days initially

Infants/Children (1 month – 12 years) 0.2 mg/kg once daily (max initial dose 5 mg) Adjust based on INR VTE: 2.0–3.0; Mechanical valve: 2.5–3.5 INR every 2–3 days → weekly → monthly

Adolescents (>12 years) 3–5 mg once daily (similar to adult) INR-guided As per indication As per adult protocol

INR Targets by Indication (Paediatric):

Indication Target INR

VTE (primary or secondary) 2.0–3.0

Mechanical mitral valve 2.5–3.5

Bioprosthetic valve (first 3 months) 2.0–3.0

Fontan/cavopulmonary shunt 2.0–3.0

Kawasaki with giant aneurysms 2.0–3.0 (often with aspirin)

Safety and Monitoring:

• Monitor INR every 2–3 days until stable, then every 1–2 weeks, then monthly

• Educate caregivers on bleeding signs, dietary consistency, drug interactions

• Vitamin K intake counselling essential

• Liquid formulations not commercially available; extemporaneous preparation may be needed

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

Antiphospholipid syndrome (paediatric) 0.1–0.2 mg/kg/day; target INR 2.0–3.0 Long-term OFF-LABEL — Specialist only; managed by paediatric rheumatology/haematology

Catheter-related thrombosis (prolonged) Weight-based; INR 2.0–3.0 3–6 months post catheter removal OFF-LABEL — Specialist only

Age Restriction Statement:

• NOT RECOMMENDED in neonates <1 month except under experienced paediatric haematology or cardiology specialist supervision

• Extreme caution required in preterm infants due to immature hepatic metabolism

Severe CKD (eGFR <30) Use with caution; increased bleeding tendency; INR may be less stable

ESRD / Haemodialysis Warfarin is NOT dialysed; can be used in dialysis patients with mechanical valves or valvular AF; preferred over DOACs in this population

Peritoneal dialysis No adjustment; INR monitoring as usual

• Active clinically significant bleeding (GI, intracranial, retroperitoneal, etc.)

• Haemorrhagic stroke (recent or ongoing)

• Severe uncontrolled hypertension (>180/110 mmHg)

• Pregnancy — 1st trimester (teratogenic) and last 4 weeks (delivery-related bleeding risk)

• Known hypersensitivity to warfarin or any coumarin derivative

• Inability to monitor INR reliably (non-compliance, remote access issues)

• Severe thrombocytopenia (<50,000/μL)

• Recent or planned neurosurgical, ophthalmic, or spinal procedures (within 72 hours)

• Unsupervised alcoholism with poor compliance

• Hepatic disease — enhanced anticoagulant effect

• Malnutrition or vitamin K deficiency — increased sensitivity

• Congestive heart failure — may affect hepatic metabolism

• Hyperthyroidism — increases warfarin catabolism of clotting factors; may need dose adjustment

• Elderly with fall risk — increased intracranial bleeding risk

• Recent surgery or trauma

• Active peptic ulcer disease (even if not currently bleeding)

• Polypharmacy — multiple drug interactions affecting INR

• Inconsistent dietary vitamin K intake

• Diarrhoeal illness — may alter vitamin K absorption and warfarin effect

• Protein C or S deficiency — risk of warfarin-induced skin necrosis at initiation; bridge with heparin

Aspect Recommendation

Risk category Contraindicated in 1st trimester and near term (Risk category: D/X depending on timing)

Fetal risks 1st trimester: Fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses, limb hypoplasia, CNS abnormalities) — risk 5–10% with exposure weeks 6–12

2nd–3rd trimester risks Fetal/neonatal haemorrhage, CNS abnormalities

Preferred alternatives LMWH (enoxaparin) throughout pregnancy in most cases

When warfarin may be used High-risk mechanical heart valves where LMWH deemed inadequate — specialist decision only; typically 2nd trimester with LMWH in 1st trimester and last 4 weeks

Monitoring Fetal anatomy scan at 18–22 weeks, serial growth scans, maternal INR, delivery planning with haematology/cardiology

Aspect Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Minimal/negligible — warfarin is highly protein-bound; transfer to breast milk is clinically insignificant

Preferred alternatives Not required; warfarin is considered safe

Infant monitoring Routine observation; monitor for unusual bruising or bleeding only if mother's INR is significantly supratherapeutic

Aspect Recommendation

Starting dose 2–3 mg once daily (lower than standard adult dose)

Titration Slower; assess INR more frequently (every 2–3 days initially)

Usual maintenance Often lower than younger adults (typically 2–5 mg/day)

Special risks Increased bleeding risk (falls, GI bleed, intracranial haemorrhage); polypharmacy; impaired renal function; cognitive impairment affecting compliance

Recommendations Fall risk assessment; medication reconciliation; caregiver education; consider pill organizers; frequent INR checks

Drug/Class Effect on Warfarin/INR Mechanism Management

Rifampicin ↓↓ INR (marked reduction) Potent CYP2C9/CYP3A4 inducer Avoid combination; if essential, increase warfarin dose significantly (may need 2–3x); monitor INR frequently

Phenytoin, Carbamazepine, Phenobarbital ↓ INR CYP inducers Monitor INR; dose adjustment required

Amiodarone ↑↑ INR (marked increase) CYP2C9 inhibition Reduce warfarin dose by 30–50% when adding amiodarone; monitor INR weekly for 4–6 weeks

Fluconazole, Voriconazole, Ketoconazole ↑↑ INR CYP2C9 inhibition Reduce warfarin dose; frequent INR monitoring

Metronidazole ↑ INR CYP inhibition Reduce dose or use short course with monitoring

NSAIDs (regular use) ↑ Bleeding risk Platelet inhibition + possible GI erosion Avoid chronic use; if needed, use lowest dose with PPI cover and closer INR monitoring

Aspirin (>100 mg/day) ↑ Bleeding risk Additive antiplatelet effect Avoid unless specific indication (e.g., mechanical valve with high risk)

Cotrimoxazole (TMP-SMX) ↑ INR CYP2C9 inhibition Reduce warfarin; monitor closely

Drug/Class Effect Management

Macrolides (Erythromycin, Clarithromycin, Azithromycin) ↑ INR Monitor INR during antibiotic course; may need dose reduction

Fluoroquinolones (Ciprofloxacin, Levofloxacin) ↑ INR Monitor INR; reduce warfarin if needed

Cephalosporins (especially cefoperazone, ceftriaxone) ↑ INR Vitamin K depletion; monitor INR

Paracetamol (>2 g/day regularly) ↑ INR (modest) Monitor INR with chronic high-dose use

Levothyroxine ↑ Warfarin effect Potentiates vitamin K-dependent factor catabolism; monitor INR after thyroid dose changes

SSRIs (Fluoxetine, Sertraline) ↑ Bleeding risk Platelet dysfunction + possible CYP interaction; monitor for bleeding signs

Statins (some) Variable; usually modest ↑ INR Monitor INR when initiating or changing statin

Omeprazole ↑ INR (modest) CYP2C19 interaction; usually minor; monitor

Herbal products (Garlic, Ginkgo, Ginger, Ginseng) Variable INR effects Counsel patients to maintain consistent intake; inform physician before use

Cranberry juice (large quantities) ↑ INR Avoid excessive consumption

• Bleeding (minor) — gum bleeding, epistaxis, easy bruising, prolonged bleeding from cuts

• Haematuria (microscopic or gross)

• Menorrhagia

• Nausea, vomiting

• Diarrhoea or abdominal discomfort

• Alopecia (with prolonged use)

• Skin rash

Adverse Effect Clinical Features Management

Major haemorrhage (GI, intracranial, retroperitoneal) Haematemesis, melaena, altered sensorium, severe headache, haematochezia, hypotension Immediate cessation; IV Vitamin K 5–10 mg slow infusion; 4-factor PCC (preferred) or FFP; ICU admission; surgical intervention if indicated

Warfarin-induced skin necrosis Painful purpuric skin lesions → necrosis; occurs days 3–8 of therapy; more common in protein C/S deficiency Stop warfarin immediately; heparinisation; vitamin K; specialist dermatology/haematology input; may require debridement

Purple toe syndrome Painful, purple discolouration of toes; cholesterol microembolism Discontinue warfarin; supportive care

Calciphylaxis (rare, in CKD patients) Painful, necrotic skin lesions Stop warfarin; specialist nephrology input

Fetal warfarin syndrome Nasal hypoplasia, skeletal abnormalities Prevention — avoid in pregnancy

After initiation INR on day 2–3, day 5, then every 2–3 days until stable within therapeutic range

After dose adjustment INR within 3–5 days of any dose change

Stable long-term therapy INR every 2–4 weeks (depending on stability); at least monthly

Additional monitoring Haemoglobin (periodically), signs of bleeding, medication reconciliation at each visit, dietary vitamin K consistency

INR Interpretation and Action:

INR Value Action

<1.5 Increase dose; reassess compliance, diet, interactions

1.5–1.9 Increase dose modestly

2.0–3.0 (or target range) Therapeutic; continue same dose

3.1–4.0 Reduce dose; recheck in 1 week; assess for bleeding

4.1–5.0 Hold 1 dose; reduce subsequent doses; recheck in 2–3 days

5.1–9.0 (no bleeding) Hold warfarin; oral Vitamin K 1–2.5 mg if high bleeding risk; recheck daily

9.0 (no bleeding) Hold warfarin; oral Vitamin K 2.5–5 mg; recheck in 24–48 hours

Any INR with serious bleeding Stop warfarin; IV Vitamin K 5–10 mg; 4-factor PCC or FFP; hospital admission

Warfarin Sodium Brands:

• Warf (Cipla)

• Sofarin (Samarth Pharma)

• Uniwarfin (Unichem)

• Marevan (Aspen — limited availability)

• Warfarin (generic — various manufacturers)

Note:

• Acitrom® contains acenocoumarol (NOT warfarin) — different VKA with shorter half-life

• Do NOT interchange warfarin with acenocoumarol without re-titration of INR; different dosing and kinetics

Notes:

• Significantly cheaper than DOACs

• Not included in NLEM 2022 (acenocoumarol is listed instead)

• Available in government hospitals in most states

• No NPPA price ceiling applicable

1. Always check baseline INR before initiating warfarin — do not assume it is normal, especially in liver disease or malnutrition.

1. LMWH bridging is mandatory at initiation — warfarin takes 4–5 days to achieve anticoagulant effect; continue LMWH until INR ≥2.0 for at least 24 hours on two consecutive measurements.

1. Dietary vitamin K counselling is essential — advise consistent (not restricted) intake of green leafy vegetables; erratic dietary changes cause INR fluctuations.

1. Do NOT switch between warfarin and acenocoumarol casually — different pharmacokinetics require complete INR re-stabilisation.

1. INR >10 without bleeding — give oral Vitamin K 2.5–5 mg and hold warfarin; do not panic or give high-dose IV vitamin K unless actively bleeding.

1. Perioperative management — for elective surgery, stop warfarin 5 days prior; bridge with LMWH if high thrombotic risk (mechanical valves, recent VTE); resume post-op when haemostasis secured.

warfarin; anticoagulant; vitamin K antagonist; VKA; INR monitoring; DVT; PE; atrial fibrillation; mechanical valve; rheumatic heart disease; pregnancy-contraindicated; bridging therapy; India

RxIndia v1.1 — 13 Jun 2025

• CDSCO-approved prescribing information

• Indian Pharmacopoeia 2022

• API Textbook of Medicine (11th Edition)

• AIIMS Anticoagulation Protocols

• MoHFW NCD Guidelines — Atrial Fibrillation

• ICMR Guidelines on Cardiovascular Disease Management

• Harrison's Principles of Internal Medicine (21st Edition)

• ACC/AHA Guidelines (for international reference where not conflicting with Indian practice)

• NLEM 2022 (reference: acenocoumarol listed; warfarin in public hospital formularies)

• Indian Society of Haematology and Blood Transfusion protocols