Schedule H

Subcutaneous (SC), Intravenous (IV — limited indications, e.g., PCI)

• Enoxaparin: 20 mg/0.2 mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL, 100 mg/1 mL prefilled syringes

• Dalteparin: 2,500 IU/0.2 mL, 5,000 IU/0.2 mL, 7,500 IU/0.3 mL prefilled syringes

• Nadroparin: 2,850 IU/0.3 mL, 5,700 IU/0.6 mL prefilled syringes

• Tinzaparin: NOT AVAILABLE in India

• Certoparin: NOT AVAILABLE in India

• Reviparin: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Note: Enoxaparin is the most widely available and studied LMWH in India. Dosing below refers primarily to Enoxaparin unless otherwise specified.

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

Parameter Recommendation

Starting dose 1 mg/kg SC every 12 hours OR 1.5 mg/kg SC once daily

Titration Not routinely required; adjust based on anti-Xa levels in special populations

Usual maintenance dose 1 mg/kg SC every 12 hours

Maximum dose Weight-based; dose-cap in obesity (consider max 100 mg per dose in morbid obesity)

Clinical Notes:

• Duration: 5–10 days; overlap with oral anticoagulant (warfarin) until INR ≥2 for at least 24 hours

• Transition to DOAC (rivaroxaban, apixaban) may be considered after initial treatment

• Monitor platelet count for HIT surveillance

• Once-daily dosing (1.5 mg/kg) may be preferred for outpatient management

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

(Post-operative, immobilised medical patients, critically ill)

Parameter Recommendation

Starting dose 40 mg SC once daily (Enoxaparin)

Titration Not applicable

Usual maintenance dose 40 mg SC once daily

Maximum dose 40 mg/day for standard prophylaxis

Clinical Notes:

• Initiate 6–12 hours post-surgery once haemostasis is secured

• Duration: 7–14 days for general surgery; extend up to 35 days for major orthopaedic surgery (hip/knee replacement)

• Reduce to 20 mg SC once daily in patients with body weight <45 kg or high bleeding risk

• For medical patients, continue until patient is ambulatory

Alternative LMWH Dosing for VTE Prophylaxis:

LMWH Prophylactic Dose

Dalteparin 2,500–5,000 IU SC once daily

Nadroparin 2,850 IU SC once daily (weight-adjusted in higher risk)

1. Acute Coronary Syndromes (Unstable Angina / NSTEMI)

Parameter Recommendation

Starting dose 1 mg/kg SC every 12 hours

Titration Not applicable

Usual maintenance dose 1 mg/kg SC every 12 hours

Maximum dose No fixed ceiling; assess renal function and bleeding risk

Clinical Notes:

• Duration: 2–8 days or until revascularisation

• Use in conjunction with dual antiplatelet therapy (aspirin + P2Y12 inhibitor)

• Reduce dose in elderly ≥75 years: 0.75 mg/kg SC every 12 hours (no initial IV bolus)

• In renal impairment (CrCl <30 mL/min): 1 mg/kg SC once daily

1. ST-Elevation Myocardial Infarction (STEMI) — With or Without Fibrinolysis

Age Group Initial Dose Maintenance Dose

<75 years 30 mg IV bolus, then 1 mg/kg SC (max 100 mg for first two doses) 1 mg/kg SC every 12 hours

≥75 years No IV bolus 0.75 mg/kg SC every 12 hours (max 75 mg for first two doses)

Clinical Notes:

• Duration: Until revascularisation or up to 8 days

• Adjust dose in renal impairment

• If PCI performed within 8 hours of last SC dose, no additional anticoagulation needed

• If PCI performed 8–12 hours after last SC dose, give additional 0.3 mg/kg IV bolus

1. Anticoagulation During Pregnancy

(Mechanical heart valves, VTE treatment/prophylaxis, thrombophilia)

Parameter Recommendation

Starting dose 1 mg/kg SC every 12 hours (therapeutic) OR 40 mg SC once daily (prophylactic)

Titration Adjust based on anti-Xa levels (target: 0.5–1.0 IU/mL for therapeutic; 0.2–0.4 IU/mL for prophylactic)

Usual maintenance dose Weight-based; reassess each trimester as weight changes

Maximum dose Individualised based on anti-Xa monitoring

Clinical Notes:

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Treatment of Venous Thromboembolism (DVT/PE), Arterial Thrombosis, Central Line-Associated Thrombosis

Note: Enoxaparin is the preferred LMWH for paediatric use in India per IAP and AIIMS protocols.

Preterm neonates 1.5–2 mg/kg every 12 hours 0.75 mg/kg every 12 hours 0.5–1.0 IU/mL (treatment)

Term neonates (<28 days) 1.5 mg/kg every 12 hours 0.75 mg/kg every 12 hours 0.5–1.0 IU/mL (treatment)

Infants (1–12 months) 1.5 mg/kg every 12 hours 0.75 mg/kg every 12 hours 0.5–1.0 IU/mL (treatment)

Children (1–5 years) 1.0 mg/kg every 12 hours 0.5 mg/kg every 12 hours 0.5–1.0 IU/mL (treatment)

Children (6–18 years) 1.0 mg/kg every 12 hours 0.5 mg/kg every 12 hours 0.5–1.0 IU/mL (treatment)

Titration:

• Check anti-Xa level 4 hours after 3rd or 4th dose

• Adjust dose by 10–25% increments to achieve target anti-Xa

• Recheck anti-Xa after each dose adjustment

Safety Monitoring:

• Baseline: CBC with platelet count, PT, aPTT, renal function, LFTs

• Platelet count every 2–3 days for first 2 weeks

• Anti-Xa levels mandatory for dose adjustment

• Monitor for bleeding (injection sites, mucous membranes, intracranial in neonates)

• Assess renal function periodically

Minimum Age: Use with caution in preterm neonates; specialist paediatric haematology supervision mandatory in neonates.

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

Indication Dose Duration Label Status Evidence Basis

Central venous catheter patency/thrombosis prophylaxis 0.5 mg/kg SC every 12–24 hours Duration of catheter placement OFF-LABEL; Specialist only IAP protocols; Indian PICU practice

Post-cardiac surgery with cannulas/mechanical support 0.5 mg/kg SC every 12 hours Until decannulation OFF-LABEL; Specialist only Paediatric cardiac surgery protocols

Kawasaki disease with coronary artery aneurysms 1 mg/kg SC every 12 hours Until transition to oral anticoagulation OFF-LABEL; Specialist only Indian paediatric cardiology practice

Age Restriction: Not recommended in preterm neonates except under specialist paediatric haematology or neonatology supervision with anti-Xa monitoring capability.

Clinical Notes:

• Calculate creatinine clearance (Cockcroft-Gault) for accurate dosing decisions

• Anti-Xa monitoring recommended if LMWH must be used in severe renal impairment

• Dalteparin and Nadroparin also require dose reduction in renal impairment; specific guidance limited in Indian literature

• UFH is preferred in severe renal dysfunction due to reversibility and non-renal clearance

• Active major bleeding (gastrointestinal, intracranial, retroperitoneal)

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

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

• Hypersensitivity to heparin, LMWH, or porcine-derived products

• Recent haemorrhagic stroke

• Severe uncontrolled hypertension

• Active bacterial endocarditis

• Recent or planned lumbar puncture, spinal, or epidural anaesthesia within inadequate time window

• Recent major surgery, trauma, or invasive procedures

• History of peptic ulcer disease or gastrointestinal bleeding

• Spinal/epidural anaesthesia — strict timing protocols required (minimum 12 hours after prophylactic dose; 24 hours after therapeutic dose before procedure)

• Elderly patients (≥75 years) — increased bleeding risk

• Low body weight (<45 kg) — consider dose reduction

• Obesity (>100 kg) — may need higher doses; consider anti-Xa monitoring

• Uncontrolled hypertension

• Diabetic retinopathy with haemorrhagic risk

• Concurrent antiplatelet therapy

• Renal impairment (CrCl <30 mL/min) — drug accumulation risk

Parameter Recommendation

Safety status Safe in pregnancy; does not cross placenta; no teratogenic effects

Preferred use LMWH is preferred anticoagulant in pregnancy over warfarin (teratogenic) and UFH (less convenient)

Indications VTE treatment/prophylaxis, mechanical heart valves, thrombophilia, antiphospholipid syndrome

Monitoring Anti-Xa levels (especially with mechanical valves); platelet count; signs of bleeding; monthly reassessment of weight for dose adjustment

Peripartum management Stop 24 hours before planned delivery; switch to UFH near term if delivery timing uncertain

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Negligible to undetectable; high molecular weight prevents significant transfer

Preferred status LMWH is preferred over warfarin in early postpartum period

Infant monitoring No specific monitoring required; observe for general health

• Starting dose: Use standard weight-based dosing for treatment; standard prophylactic doses acceptable

• Age ≥75 years with ACS/STEMI: Reduce dose to 0.75 mg/kg SC every 12 hours (no IV bolus)

• Titration: Not routinely required; reassess renal function before and during therapy

• Extra risks:

• Increased bleeding risk due to age-related vascular fragility

• Declining renal function — recalculate CrCl frequently

• Higher fall risk — assess and counsel

• Polypharmacy — review for drug interactions

• Increased sensitivity to anticoagulant effects

• Monitoring: More frequent CBC, renal function assessment, and clinical bleeding surveillance

Interacting Drug/Class Mechanism/Effect Recommendation

Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) Synergistic bleeding risk Essential in ACS; monitor closely; avoid high-dose aspirin

Oral anticoagulants (warfarin, acenocoumarol) Additive anticoagulation Brief overlap during transition only; monitor INR

Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran, edoxaban) Excessive anticoagulation Avoid concurrent use; sequential use per protocol

Thrombolytics (alteplase, streptokinase, tenecteplase) Markedly increased haemorrhage risk Use sequentially, not concurrently; follow protocol timing

GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) Synergistic bleeding Dose adjustments per PCI protocols

Dextran Additive anticoagulant effect Avoid combination

Interacting Drug/Class Mechanism/Effect Recommendation

NSAIDs (diclofenac, ibuprofen, naproxen) Increased GI bleeding risk; platelet inhibition Avoid if possible; use short course with monitoring

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

Corticosteroids (prolonged use) Increased GI bleeding risk Monitor for GI symptoms

Cephalosporins with MTT side chain (cefoperazone, cefotetan) Vitamin K antagonism; increased bleeding Monitor coagulation

Antitubercular drugs (rifampicin) May alter metabolism of oral anticoagulants during overlap Monitor INR if transitioning to warfarin

Valproic acid Platelet dysfunction Monitor for bleeding

• Injection site pain, bruising, and haematoma (10–20%)

• Minor bleeding (gingival bleeding, epistaxis, haematuria)

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

• Transient elevation of hepatic transaminases

• Local skin irritation at injection site

• Heparin-induced thrombocytopenia (HIT) type II: Immune-mediated; typically day 5–14; paradoxical thrombosis; requires immediate discontinuation and alternative anticoagulation (fondaparinux, argatroban)

• Major haemorrhage: Intracranial, retroperitoneal, gastrointestinal — requires discontinuation; partial reversal with protamine sulfate (60–80% neutralisation)

• Spinal/Epidural haematoma: Associated with neuraxial anaesthesia; can cause permanent paralysis; strict timing protocols essential

• Skin necrosis at injection site: Rare

• Osteoporosis: With prolonged use (>3 months); less common than with UFH

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

• Anaphylaxis: Rare hypersensitivity reaction

After initiation (first 2 weeks) Platelet count every 2–3 days (HIT surveillance)

Anti-Xa monitoring (when indicated) 4 hours post-dose; in pregnancy, obesity, extremes of weight, renal impairment, paediatrics

Long-term use Periodic CBC, renal function; bone density if use >3 months

Clinical Daily assessment for bleeding, injection site complications

Anti-Xa Target Levels:

Indication Target Anti-Xa (IU/mL) — 4 hours post-dose

Therapeutic (twice daily dosing) 0.5–1.0

Therapeutic (once daily dosing) 1.0–2.0

Prophylactic 0.2–0.4

Enoxaparin:

• Clexane® (Sanofi)

• Lonopin® (Abbott)

• Enclex® (Cipla)

• Lupenox® (Lupin)

• Enoxaparin Injection IP (Alkem, Intas, Glenmark, multiple generics)

Dalteparin:

• Fragmin® (Pfizer)

Nadroparin:

• Fraxiparine® (Aspen)

Note: Multiple generic enoxaparin formulations available; confirm dosage equivalence and bioequivalence before switching brands. LMWHs are not interchangeable with each other.

NLEM Status: Enoxaparin (6,000 IU injection) is included in NLEM 2022; NPPA price-controlled for ceiling prices.

Government Supply: Available through government hospitals and NHM procurement.

• Enoxaparin is the most widely available and best-studied LMWH in India; use it as the default choice unless specific indications favour alternatives

• LMWHs are not interchangeable — do not switch between enoxaparin, dalteparin, and nadroparin during a treatment course

• Anti-Xa monitoring is not routine but essential in: pregnancy (especially mechanical valves), extremes of body weight, renal impairment, paediatrics, and when therapeutic efficacy is uncertain

• Always calculate creatinine clearance before initiating LMWH, especially in elderly patients — even "normal" serum creatinine may mask significant renal impairment

• Strict timing protocols must be followed for neuraxial procedures: minimum 12 hours after prophylactic dose, 24 hours after therapeutic dose; reinitiate 4–6 hours after catheter removal

• Protamine sulfate provides only partial reversal (60–80%) of LMWH; in life-threatening bleeding, give protamine 1 mg per 1 mg enoxaparin (if given within 8 hours); consider anti-Xa levels and additional supportive measures

anticoagulant; LMWH; enoxaparin; dalteparin; nadroparin; DVT; PE; VTE prophylaxis; ACS; STEMI; pregnancy-safe; renal-adjust; NLEM India; HIT risk

RxIndia v1.0 — 29 May 2025

• CDSCO product information

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022

• AIIMS Drug Formulary and Anticoagulation Guidelines

• API Textbook of Medicine

• IAP Guidelines for Paediatric Thrombosis Management

• ICMR/National Guidelines for Management of VTE

• Cardiological Society of India (CSI) ACS Management Guidelines

• NCG Guidelines for Cancer-Associated Thrombosis

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