Schedule H

Intravenous (IV), Subcutaneous (SC)

• Injection: 5,000 IU/mL (1 mL, 5 mL vials/ampoules)

• Injection: 25,000 IU/5 mL (5 mL vials)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Venous Thromboembolism (VTE) Prophylaxis in High-Risk Patients

Parameter Recommendation

Starting dose 5,000 IU SC

Titration Not applicable

Usual maintenance dose 5,000 IU SC every 8–12 hours

Maximum dose 5,000 IU every 8 hours

Clinical Notes:

• Initiate post-operatively once haemostasis is secured

• Continue until patient is ambulatory or transitioned to oral anticoagulation

• No aPTT monitoring required for prophylactic dosing

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

Weight-based Protocol (Preferred):

Parameter Recommendation

Starting dose 80 IU/kg IV bolus

Titration Adjust infusion rate every 6 hours based on aPTT (target: 1.5–2.5× control or 60–80 seconds)

Usual maintenance dose 18 IU/kg/hour continuous IV infusion

Maximum dose Titrate to therapeutic aPTT; no fixed ceiling

Fixed-dose Protocol (Alternative):

Parameter Recommendation

Starting dose 5,000–10,000 IU IV bolus

Titration Adjust based on aPTT every 6 hours until stable

Usual maintenance dose 1,000–1,500 IU/hour continuous IV infusion

Maximum dose As per aPTT response

Clinical Notes:

• Check aPTT 6 hours after initiation and after each dose adjustment

• Once stable, monitor aPTT daily

• Overlap with oral anticoagulant (warfarin) for minimum 5 days and until INR ≥2 for 24 hours

1. Acute Coronary Syndromes (Unstable Angina / NSTEMI)

Parameter Recommendation

Starting dose 60–70 IU/kg IV bolus (maximum 5,000 IU)

Titration Adjust infusion based on aPTT (target: 1.5–2.5× control)

Usual maintenance dose 12–15 IU/kg/hour IV infusion (maximum 1,000 IU/hour)

Maximum dose 1,000 IU/hour (higher doses increase bleeding without added benefit)

Clinical Notes:

• Duration: 2–5 days or until revascularisation

• Co-administer with antiplatelet therapy (aspirin ± P2Y12 inhibitor) as per ACS protocol

• Monitor for bleeding complications at vascular access sites

1. Anticoagulation During Percutaneous Coronary Intervention (PCI)

Parameter Recommendation

Starting dose 70–100 IU/kg IV bolus (without GP IIb/IIIa inhibitor) OR 50–70 IU/kg IV bolus (with GP IIb/IIIa inhibitor)

Titration Additional boluses guided by ACT

Usual maintenance dose Not applicable (bolus-only protocol)

Maximum dose Guided by ACT (target: 250–350 seconds without GP IIb/IIIa; 200–250 seconds with GP IIb/IIIa)

1. Anticoagulation During Cardiopulmonary Bypass (CPB)

Parameter Recommendation

Starting dose 300–400 IU/kg IV bolus before cannulation

Titration Additional boluses to maintain ACT >400–480 seconds

Usual maintenance dose As per intra-operative ACT monitoring

Maximum dose Guided by ACT; typically 600 IU/kg total may be required

Clinical Notes:

• Protamine reversal required post-bypass

• Protamine dose: 1 mg per 100 IU of heparin administered

1. Anticoagulation During Haemodialysis

Parameter Recommendation

Starting dose 1,000–2,000 IU IV bolus at initiation

Titration Additional 500–1,000 IU if session prolonged

Usual maintenance dose 500–1,000 IU/hour during dialysis

Maximum dose Individualised based on clotting in circuit

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Treatment of DVT/PE in Children

Neonates (<28 days) 75–100 IU/kg 28 IU/kg/hour 60–85 seconds

Infants (28 days–1 year) 75 IU/kg 20 IU/kg/hour 60–85 seconds

Children (>1 year) 75 IU/kg 18 IU/kg/hour 60–85 seconds

Titration Protocol:

• Check aPTT 4–6 hours after initiation

• Adjust infusion by 10–25% increments based on aPTT

• Recheck aPTT 4–6 hours after each dose change until stable

Safety Monitoring:

• Platelet count at baseline, day 3, and then every 2–3 days

• Monitor for signs of bleeding (mucosal, injection sites, intracranial in neonates)

• Anti-Xa levels may be used if aPTT unreliable (target: 0.35–0.7 IU/mL)

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Label Status Evidence Basis

Central venous catheter patency (flush) 10 IU/mL; flush every 8–12 hours As long as catheter in situ OFF-LABEL; Specialist only Indian PICU practice; IAP recommendations

Kawasaki disease with coronary aneurysm Weight-based therapeutic protocol Until transition to LMWH or warfarin OFF-LABEL; Specialist only Indian paediatric cardiology practice

Age Restriction: Not recommended in neonates except under specialist haematology or neonatology supervision with appropriate monitoring facilities.

• Active major bleeding (gastrointestinal, intracranial, retroperitoneal)

• Severe uncontrolled hypertension

• History of heparin-induced thrombocytopenia (HIT) type II

• Hypersensitivity to heparin or porcine-derived products

• Recent haemorrhagic stroke or intracranial haemorrhage

• Severe thrombocytopenia (platelet count <50,000/μL unless thrombotic emergency)

• Recent lumbar puncture or spinal anaesthesia (within 12–24 hours)

• Threatened abortion

• Recent major surgery or trauma (within 7–14 days)

• Active peptic ulcer disease or history of GI bleeding

• Severe liver disease with coagulopathy

• Bacterial endocarditis

• Diabetic retinopathy with risk of vitreous haemorrhage

• Concurrent use of antiplatelet agents

• Indwelling epidural catheters

• Advanced age (>75 years) — increased bleeding risk

• History of allergy to beef or pork products

• Prior exposure to heparin within 100 days — increased HIT risk

Parameter Recommendation

Safety status Safe in pregnancy — does not cross placenta

Preferred use Anticoagulant of choice for VTE treatment/prophylaxis and mechanical heart valves during pregnancy

Alternatives LMWH is more commonly used due to convenient dosing; UFH preferred near delivery for reversibility

When to use Throughout pregnancy; switch from LMWH to UFH at 36 weeks or before planned delivery

Monitoring aPTT (therapeutic dosing); platelet count every 2–3 days; signs of bleeding; osteoporosis risk with prolonged use

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Negligible; large molecular weight prevents transfer

Preferred alternative LMWH is equally safe; both acceptable

Infant monitoring No specific monitoring required

• Starting dose: Use lower end of dosing range; consider 60 IU/kg bolus and 15 IU/kg/hour infusion for therapeutic anticoagulation

• Titration: More gradual; increase intervals between dose adjustments

• Extra risks:

• Increased bleeding risk due to age-related vascular fragility

• Reduced renal reserve affecting drug handling

• Higher incidence of falls and trauma

• Greater sensitivity to anticoagulant effect

• Polypharmacy increasing interaction risk

• Monitoring: More frequent aPTT checks; vigilant clinical monitoring for bleeding

Interacting Drug/Class Mechanism/Effect Recommendation

Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) Synergistic bleeding risk Use cautiously; essential in ACS protocols but monitor closely

Oral anticoagulants (warfarin, acenocoumarol) Additive anticoagulation Overlap briefly during transition; monitor INR and aPTT

Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) Excessive anticoagulation Avoid concurrent use except during protocol-guided transitions

Thrombolytics (alteplase, streptokinase, tenecteplase) Markedly increased bleeding Use sequentially, not concurrently; heparin started after thrombolysis per protocol

GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) Synergistic bleeding Reduce heparin dose during PCI; monitor ACT

Dextran Additive anticoagulant effect Avoid combination

Interacting Drug/Class Mechanism/Effect Recommendation

NSAIDs (diclofenac, ibuprofen, naproxen) Increased GI bleeding risk; platelet inhibition Monitor for bleeding; avoid if possible

SSRIs/SNRIs (fluoxetine, sertraline, venlafaxine) Impaired platelet function Monitor for bleeding

Nitroglycerin (IV) May reduce heparin effect; mechanism unclear May require higher heparin doses; monitor aPTT

Penicillins (high-dose piperacillin, ticarcillin) Platelet dysfunction Monitor bleeding time and clinical signs

Tetracyclines, antihistamines May interfere with aPTT assay Interpret aPTT cautiously

• Bleeding (injection site haematoma, gingival bleeding, epistaxis, haematuria)

• Injection site pain and erythema (SC administration)

• Mild transient thrombocytopenia (non-immune, within first 2 days)

• Elevated transaminases (mild, reversible)

• Bruising

• Heparin-induced thrombocytopenia (HIT) type II: Immune-mediated; platelet drop >50% from baseline typically day 5–10; paradoxically causes thrombosis — discontinue heparin immediately; initiate alternative anticoagulant (argatroban, fondaparinux)

• Major haemorrhage: Intracranial, retroperitoneal, GI — requires protamine reversal and supportive care

• Osteoporosis: With prolonged use (>1 month); vertebral fractures reported

• Skin necrosis: At injection sites; rare

• Hypersensitivity reactions: Urticaria, anaphylaxis (rare)

• Hyperkalaemia: Due to aldosterone suppression; monitor potassium in prolonged use

After initiation/dose change aPTT every 6 hours until therapeutic and stable (2 consecutive values in range)

Ongoing (therapeutic dosing) aPTT daily once stable; platelet count every 2–3 days for first 14 days (HIT surveillance)

Ongoing (prophylactic dosing) Platelet count every 2–3 days; no routine aPTT required

Prolonged use (>1 month) Consider bone density monitoring; serum potassium

Clinical Daily assessment for bleeding, thrombosis, injection site reactions

• Heparin Sodium Injection IP (Gland Pharma, Biological E, Gufic, VHB Lifesciences)

• Heparin Leo® (Leo Pharma)

• Beparine® (Troikaa)

• Hepaglan® (Gland Pharma)

• Multiple institutional and generic manufacturers

NLEM Status: Included in NLEM 2022; available through government supply under NHM and institutional procurement.

• UFH is preferred over LMWH in severe renal impairment (eGFR <30 mL/min), high bleeding risk situations, and when rapid reversibility is needed (surgery, delivery)

• Protamine sulfate reverses UFH: 1 mg neutralises approximately 100 IU of heparin given in the preceding hour; reduce dose for heparin given earlier

• HIT typically occurs day 5–14 of exposure; always check prior heparin exposure history — patients exposed within 100 days may develop rapid-onset HIT

• Weight-based dosing protocols achieve therapeutic aPTT faster and more reliably than fixed-dose protocols

• In obese patients, use actual body weight for bolus but consider dose-capping the infusion rate

• Never mix heparin with other IV medications unless compatibility is confirmed; use dedicated IV line or flush between drugs

anticoagulant; UFH; heparin; DVT; PE; ACS; STEMI; NSTEMI; cardiopulmonary bypass; haemodialysis; HIT; pregnancy-safe; NLEM India; renal-safe

RxIndia v1.0 — 28 May 2025

• CDSCO product information

• Indian Pharmacopoeia

• NLEM 2022

• AIIMS Anticoagulation Guidelines

• API Textbook of Medicine

• ICMR/National Guidelines for Management of VTE

• Indian Society of Haematology and Blood Transfusion (ISHBT) protocols

• Cardiological Society of India (CSI) ACS management guidelines