Schedule H

Oral

Formulations Available in India:

• Tablets: 75 mg, 150 mg, 300 mg

• Fixed-dose combinations (FDCs): Clopidogrel 75 mg + Aspirin 75 mg; Clopidogrel 75 mg + Aspirin 150 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Coronary Syndrome (ACS) — NSTEMI / Unstable Angina

Parameter Recommendation

Starting dose (Loading) 300 mg orally as single dose

Titration Not applicable

Usual maintenance dose 75 mg once daily

Maximum dose 75 mg once daily

Clinical Notes:

• Administer with aspirin (75–100 mg/day) unless contraindicated

• Duration: Minimum 12 months (DAPT — dual antiplatelet therapy)

• Continue aspirin indefinitely; clopidogrel may be stopped after 12 months in stable patients

• Consider higher loading dose (600 mg) if planned for early invasive strategy/PCI

1. ST-Elevation Myocardial Infarction (STEMI) — Treated with Thrombolytics

Parameter Age <75 years Age ≥75 years

Starting dose (Loading) 300 mg orally No loading dose (omit)

Titration Not applicable Not applicable

Usual maintenance dose 75 mg once daily 75 mg once daily

Maximum dose 75 mg once daily 75 mg once daily

Clinical Notes:

• Administer with aspirin (loading 325 mg, then 75–100 mg daily)

• Duration: Minimum 14 days; up to 12 months recommended

• Based on CLARITY-TIMI 28 and Indian STEMI guidelines

• Loading dose omitted in elderly (≥75 years) due to increased bleeding risk per Indian cardiology practice

1. Percutaneous Coronary Intervention (PCI) with Stent Placement

Parameter Elective PCI Primary PCI (STEMI)

Starting dose (Loading) 300–600 mg orally 600 mg orally (preferred)

Titration Not applicable Not applicable

Usual maintenance dose 75 mg once daily 75 mg once daily

Maximum dose 75 mg once daily 75 mg once daily

Duration of DAPT (with Aspirin):

Stent Type Minimum Duration Recommended Duration

Bare-metal stent (BMS) 1 month 1–3 months

Drug-eluting stent (DES) 6 months 6–12 months

High bleeding risk patients May shorten to 1–3 months Specialist decision

High ischaemic risk patients May extend beyond 12 months Specialist decision

Clinical Notes:

• 600 mg loading achieves faster platelet inhibition than 300 mg

• Co-administer with aspirin (75–100 mg daily)

• Pre-treatment with clopidogrel preferred if PCI planned within 24–48 hours

1. Secondary Prevention of Atherothrombotic Events (Post-MI, Ischaemic Stroke, PAD)

Parameter Recommendation

Starting dose 75 mg once daily (no loading dose required)

Titration Not applicable

Usual maintenance dose 75 mg once daily

Maximum dose 75 mg once daily

Clinical Notes:

• May be used as monotherapy or with aspirin in selected high-risk cases

• Duration: Long-term (often indefinite) based on cardiovascular risk

• Alternative to aspirin in patients with aspirin intolerance

• In PAD: reduces risk of MI, stroke, and vascular death

Secondary Indications — Adults Only (Off-label)

Indication Loading Dose Maintenance Dose Duration Notes

Minor Ischaemic Stroke / High-risk TIA (DAPT) — OFF-LABEL 300 mg clopidogrel + aspirin 75–100 mg 75 mg clopidogrel + aspirin 75–100 mg daily 21–30 days, then switch to single antiplatelet Specialist (Neurology) only. Initiate within 24 hours of symptom onset. Based on CHANCE and POINT trials. AIIMS Neurology protocol. Reduces recurrent stroke risk by ~25%.

Atrial Fibrillation (unable to take oral anticoagulants) — OFF-LABEL Not applicable 75 mg daily with aspirin 75–100 mg Long-term Specialist only. Inferior to OAC but reduces stroke risk vs aspirin alone. Based on ACTIVE-A trial. Reserve for patients unsuitable for anticoagulation.

Coronary Artery Bypass Graft (CABG) — Post-operative — OFF-LABEL Not applicable 75 mg once daily 12 months typically Specialist only. Used in saphenous vein graft protection. Limited evidence; based on institutional practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

No approved routine indication in children in India.

Secondary Indications — Paediatric (Off-label)

Indication Age/Weight Dose Duration Notes

Paediatric Arterial Ischaemic Stroke — OFF-LABEL >1 month; any weight 0.2–1 mg/kg/dose once daily (maximum 75 mg/day) Variable; often long-term in selected cases Paediatric neurologist or haematologist only. Based on limited observational data and IAP neurological protocols. Individualise based on stroke aetiology.

Kawasaki Disease with Giant Coronary Aneurysms — OFF-LABEL >6 months 1 mg/kg/day (max 75 mg) Long-term; often combined with aspirin Paediatric cardiologist only. Added to aspirin in high-risk coronary involvement. Based on AHA guidelines adapted to Indian practice.

Systemic-to-Pulmonary Artery Shunts (e.g., BT shunt) — OFF-LABEL Neonates onwards 0.2 mg/kg/day Until shunt takedown Paediatric cardiac surgery/cardiology only. Limited data; institutional protocols.

Dosing Structure (General Paediatric Off-label Use):

Parameter Recommendation

Starting dose 0.2 mg/kg/day orally

Titration Increase to 1 mg/kg/day based on indication and response

Usual maintenance dose 0.5–1 mg/kg/day

Maximum dose 75 mg/day

Age Restrictions:

• Not recommended below 1 month of age except under specialist supervision in cardiac surgical cases

• Tablets may need to be crushed/dispersed for administration in young children — confirm stability

Safety Monitoring in Children:

• Monitor for bleeding manifestations (bruising, petechiae, gum bleeding, haematuria)

• Periodic CBC if long-term use (baseline, 2 weeks, then every 3–6 months)

• Assess for signs of TTP (thrombocytopenia, neurological symptoms, renal impairment)

• Drug compliance — liquid formulations not readily available in India

60 No dose adjustment required

30–60 No dose adjustment required

15–30 Use with caution; no specific dose reduction but increased bleeding risk

<15 / Dialysis Limited data; use with caution. Not significantly removed by haemodialysis. Monitor for bleeding.

• Active pathological bleeding (intracranial haemorrhage, active GI bleeding, haemorrhagic stroke)

• Known hypersensitivity to clopidogrel or any formulation component

• Severe hepatic impairment (Child-Pugh C)

• History of thrombotic thrombocytopenic purpura (TTP) associated with clopidogrel or other thienopyridines (ticlopidine)

• Recent major surgery or trauma (within 7 days) — increased bleeding risk

• History of gastrointestinal bleeding or peptic ulcer disease

• Concurrent use of anticoagulants (warfarin, DOACs, heparin)

• Concurrent NSAID use — increased GI bleeding risk

• Patients with bleeding diathesis or thrombocytopenia

• CYP2C19 poor metaboliser status — reduced drug efficacy (genetic polymorphism common in Indian population)

• Planned elective surgery — discontinue 5–7 days prior

• Elderly patients (increased bleeding risk)

• Concurrent use of CYP2C19 inhibitors (e.g., omeprazole, esomeprazole)

• Moderate hepatic impairment

• Renal impairment (enhanced surveillance needed)

Parameter Information

Overall safety Limited human data; animal studies show no teratogenicity

Risk assessment Use only if potential benefit clearly outweighs risk

Preferred alternatives Low-dose aspirin (75–150 mg) is preferred antiplatelet in pregnancy when indicated

When may be used Compelling indications (e.g., recent coronary stent, mechanical heart valve with aspirin intolerance) — specialist decision only

Monitoring Maternal bleeding risk; fetal growth; discontinue 7 days before expected delivery to reduce peripartum haemorrhage

Parameter Information

Compatibility Likely compatible with breastfeeding; limited human data

Milk levels Expected to be low (based on pharmacokinetic profile — highly protein-bound)

Preferred alternatives Low-dose aspirin if antiplatelet therapy required

Infant monitoring Observe for unusual bruising, bleeding, petechiae; monitor feeding and weight gain

Parameter Recommendation

Starting dose 75 mg once daily for maintenance

Loading dose Use 300 mg with caution; avoid loading dose in patients ≥75 years with STEMI treated with thrombolytics

Titration Not applicable

Special considerations Higher bleeding risk; increased fall risk (bruising, haematoma); reduced renal reserve

Polypharmacy Review concurrent medications for interactions (PPIs, anticoagulants, NSAIDs)

Monitoring More frequent assessment for bleeding; periodic CBC and renal function

Drug/Class Interaction Mechanism Management

Omeprazole, Esomeprazole Reduced clopidogrel efficacy; increased cardiovascular events risk CYP2C19 inhibition reduces conversion to active metabolite Avoid combination. Use pantoprazole or rabeprazole (minimal CYP2C19 inhibition) instead.

Warfarin Significantly increased bleeding risk Additive anticoagulant/antiplatelet effects Avoid unless strongly indicated (e.g., mechanical valve + recent ACS). Triple therapy should be time-limited. INR monitoring essential.

DOACs (rivaroxaban, apixaban, dabigatran) Increased bleeding risk Additive effects Avoid routine combination. If required (AF + recent stent), use lowest DOAC dose and limit duration. Specialist supervision.

Rifampicin May paradoxically increase active metabolite levels acutely but reduce overall efficacy with chronic use CYP inducer affecting prodrug activation Monitor for both increased bleeding (short-term) and reduced efficacy (long-term). Consider alternative antiplatelet if prolonged rifampicin course.

Strong CYP2C19 inhibitors (fluconazole, fluoxetine, fluvoxamine) Reduced clopidogrel efficacy Inhibit metabolic activation Avoid if possible. Consider alternative antifungal/antidepressant or alternative antiplatelet (prasugrel, ticagrelor — not CYP2C19 dependent).

Drug/Class Interaction Management

Aspirin Increased bleeding risk (especially GI) Routine combination in ACS/post-PCI. Co-prescribe PPI (pantoprazole preferred) for gastroprotection.

NSAIDs (ibuprofen, diclofenac, naproxen) Increased GI bleeding risk Avoid if possible. If needed, use short-term with PPI cover.

SSRIs (sertraline, paroxetine, citalopram) Additive bleeding risk Monitor for bleeding. Consider gastroprotection. Paroxetine may also inhibit CYP2D6.

Atorvastatin Theoretical CYP3A4 competition Clinical impact minimal. No dose adjustment needed.

Diltiazem, Verapamil Mild CYP3A4 inhibition Usually no dose change required. Monitor clinical response.

Phenytoin, Carbamazepine, Phenobarbital May reduce clopidogrel efficacy CYP induction. Monitor for recurrent ischaemic events. Consider platelet function testing if available.

Morphine (in ACS setting) Delayed clopidogrel absorption; reduced antiplatelet effect Consider crushed tablets or alternative P2Y12 inhibitors (ticagrelor, cangrelor) in primary PCI if morphine required.

• Bleeding (minor) — bruising, epistaxis, gum bleeding

• Dyspepsia, abdominal pain

• Diarrhoea

• Rash, pruritus

• Headache

Effect Notes

Major bleeding GI haemorrhage, retroperitoneal bleeding — requires discontinuation and supportive care. No specific antidote; platelet transfusion may be considered.

Intracranial haemorrhage Rare but life-threatening. Discontinue immediately. Emergency neurosurgical assessment.

Thrombotic Thrombocytopenic Purpura (TTP) Rare (1 in 250,000); usually within first 2 weeks. Presents with thrombocytopenia, microangiopathic haemolytic anaemia, neurological symptoms, renal impairment, fever. Discontinue immediately. Urgent haematology referral. Plasma exchange required.

Severe neutropenia / Agranulocytosis Rare. Monitor if unexplained fever or infection. Discontinue if confirmed.

Stevens-Johnson Syndrome / TEN Very rare. Discontinue immediately if mucocutaneous reaction develops.

Hepatotoxicity Rare; cholestatic or hepatocellular. Monitor LFTs if symptomatic.

After initiation Clinical assessment for bleeding at each visit; CBC if bleeding suspected

Long-term (>6–12 months) Periodic CBC (every 6–12 months); renal and hepatic function annually or as indicated

Special situations CYP2C19 genotyping: Not routine, but consider in treatment failure, recurrent thrombotic events despite compliance, or family history of clopidogrel resistance. Platelet function testing (e.g., VerifyNow) may be available at tertiary centres.

Pre-operative:

• Discontinue 5–7 days before elective surgery

• Urgent surgery: Proceed with awareness of bleeding risk; platelet transfusion if severe bleeding

Single Ingredient:

• Clopivas (Cipla)

• Deplatt (Torrent)

• Clopilet (Sun Pharma)

• Plavix (Sanofi)

• Clopitab (Lupin)

• Clopid (Zydus)

• Plagril (USV)

Fixed-Dose Combinations (with Aspirin):

• Clopivas-A, Clopivas-AP (Cipla)

• Deplatt-A, Deplatt-CV (Torrent)

• Clopilet-A (Sun Pharma)

• Ecosprin-AV (USV) — aspirin + atorvastatin + clopidogrel

Note: 150 mg and 300 mg tablets available for loading doses from select manufacturers.

Note: Clopidogrel 75 mg is included in NLEM 2022 and under NPPA price control. Available in government supply and Jan Aushadhi outlets at reduced cost.

1. PPI selection matters: Always avoid omeprazole and esomeprazole with clopidogrel due to CYP2C19 interaction. Prefer pantoprazole or rabeprazole — they have minimal interaction and provide adequate gastroprotection during DAPT.

1. Loading dose in elderly STEMI: Omit the 300 mg loading dose in patients ≥75 years receiving thrombolytics — bleeding risk outweighs benefit. Maintenance dose of 75 mg remains appropriate.

1. CYP2C19 polymorphism: Approximately 25–30% of the Indian population are poor metabolisers (CYP2C192/3 carriers) with reduced clopidogrel response. Consider prasugrel or ticagrelor in high-risk ACS patients, particularly post-PCI, if available and affordable.

1. DAPT duration flexibility: Standard DAPT duration post-DES is 6–12 months, but can be shortened (1–3 months) in high bleeding risk or extended (>12 months) in high ischaemic risk patients based on individualised assessment.

1. Pre-operative planning: Discontinue clopidogrel 5–7 days before elective surgery. For semi-urgent surgery, balance bleeding vs thrombotic risk — may proceed after 3–5 days in consultation with cardiology.

1. Morphine interaction in primary PCI: Morphine delays clopidogrel absorption. Consider crushed tablets via NG tube or alternative P2Y12 inhibitors (ticagrelor, cangrelor) in STEMI undergoing primary PCI.

clopidogrel; antiplatelet; P2Y12 inhibitor; ACS; STEMI; NSTEMI; PCI; stent; stroke prevention; DAPT; NLEM India; bleeding risk; CYP2C19; elderly-caution

RxIndia v1.0 — 05 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022

• API Textbook of Medicine

• ICMR-INDIAB STEMI Guidelines

• AIIMS Cardiology and Neurology protocols

• Cardiological Society of India (CSI) ACS guidelines

• Indian Stroke Association consensus statements

• CLARITY-TIMI 28, CURE, COMMIT trials

• CHANCE and POINT trials (for off-label TIA/minor stroke indication)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics