Schedule H

Intravenous

• Integrilin® 20 mg/10 mL (2 mg/mL) vial for IV injection

• Integrilin® 75 mg/100 mL (0.75 mg/mL) infusion bag

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

⚫ Acute Coronary Syndrome (Unstable Angina / NSTEMI) — Medical or PCI Management

Parameter Dose Clinical Notes

Starting dose (Initial bolus) 180 mcg/kg IV bolus over 1–2 minutes Administer as early as possible before planned PCI

Titration Not applicable —

Usual maintenance dose 2 mcg/kg/min continuous infusion Duration: up to 72 hours OR until hospital discharge/end of PCI (whichever earlier)

Maximum dose 2 mcg/kg/min infusion; reduce to 1 mcg/kg/min if CrCl <50 mL/min —

Repeat bolus (PCI planned) Second 180 mcg/kg IV bolus 10 minutes after initial bolus Enhances platelet inhibition during procedure

⚫ Adjunct During Percutaneous Coronary Intervention (PCI)

Parameter Dose Clinical Notes

Starting dose 180 mcg/kg IV bolus over 1–2 minutes Administer immediately before or during PCI

Titration Not applicable —

Usual maintenance dose 2 mcg/kg/min continuous infusion for 18–24 hours post-PCI Reduces thrombotic complications

Maximum dose 2 mcg/kg/min; reduce to 1 mcg/kg/min if CrCl <50 mL/min —

Repeat bolus Second 180 mcg/kg IV bolus 10 minutes after first bolus Mandatory for optimal PCI platelet inhibition

Key Clinical Notes:

• Must be co-administered with aspirin and unfractionated heparin unless contraindicated

• May be used intra-procedurally during PCI

• Ensure catheterisation laboratory facilities available before initiation

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

Not applicable.

No established off-label indications in Indian clinical practice. Use outside ACS/PCI settings is not recommended.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

Safety and efficacy not established in patients below 18 years of age. Eptifibatide is not recommended for paediatric use.

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

Not applicable.

Use only in clinical trial settings or specialist-led research protocols at tertiary cardiac centres.

Age Restriction: Not recommended below 18 years of age.

Creatinine Clearance Bolus Dose Maintenance Infusion Clinical Notes

≥50 mL/min 180 mcg/kg (no change) 2 mcg/kg/min No adjustment required

30–49 mL/min 180 mcg/kg (no change) 1 mcg/kg/min Reduce maintenance infusion by 50%

<30 mL/min Avoid use Avoid use Relative contraindication in Indian practice

Dialysis-dependent Contraindicated Contraindicated Drug not dialyzable; significantly increased bleeding risk

• Active internal bleeding or recent significant gastrointestinal/genitourinary bleeding

• Known bleeding diathesis or coagulation disorders

• History of haemorrhagic stroke (ever) or any stroke within past 30 days

• Severe uncontrolled hypertension (systolic >200 mmHg or diastolic >110 mmHg)

• Major surgery, trauma, or head injury within past 6 weeks

• Baseline thrombocytopenia (platelet count <100,000/mm³)

• Renal dialysis dependence or CrCl <30 mL/min (relative contraindication per Indian practice)

• Known hypersensitivity to eptifibatide or any excipients

• Intracranial neoplasm, arteriovenous malformation, or aneurysm

• Concurrent use of another glycoprotein IIb/IIIa inhibitor

• Concurrent use with other antithrombotics (heparin, aspirin, clopidogrel) — increases bleeding risk; requires close monitoring

• Elderly patients — inherently higher bleeding risk

• Recent lumbar puncture, epidural anaesthesia, or spinal procedure

• Recent arterial puncture at non-compressible site (e.g., subclavian, jugular)

• Recent organ biopsy

• Minimise invasive procedures and arterial/venous punctures during infusion

• Ensure adequate vascular access management (femoral sheath care)

• Patients with body weight <60 kg — may have increased bleeding tendency

Parameter Details

Risk Category Limited human data; presumed risk

Overall Safety Not routinely used during pregnancy; avoid unless benefit clearly outweighs risk

Preferred Alternatives Unfractionated heparin with low-dose aspirin if antiplatelet therapy needed

When May Be Used Only in life-threatening ACS with PCI where no alternatives exist; specialist decision only

Monitoring Maternal bleeding parameters; fetal heart rate monitoring for distress

Parameter Details

Compatibility Unknown; not recommended

Excretion in Milk Not known if excreted in human breast milk

Expected Levels in Milk Data not available

Preferred Alternatives Heparin or aspirin if antiplatelet therapy required postpartum

Infant Monitoring If inadvertently used: monitor for bleeding signs, bruising, feeding difficulties

Parameter Recommendation

Starting dose Same as adults (180 mcg/kg bolus)

Titration Not applicable

Maintenance dose 2 mcg/kg/min (reduce to 1 mcg/kg/min if CrCl <50 mL/min)

Special Considerations Higher bleeding risk — monitor closely

Additional Monitoring Assess renal function before and during therapy; falls risk assessment before initiation; more frequent platelet count monitoring

Interacting Drug Effect/Mechanism Recommendation

Thrombolytics (alteplase, reteplase, tenecteplase) Markedly increased bleeding risk through dual fibrinolytic and antiplatelet effects Avoid concurrent use

Other GPIIb/IIIa inhibitors (abciximab, tirofiban) Severe additive thrombocytopenia and bleeding Do not combine — contraindicated

Warfarin/Acenocoumarol Additive anticoagulant effect Avoid concurrent use if possible; if unavoidable, monitor INR closely and watch for bleeding

Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) Significantly increased bleeding risk Avoid concurrent use unless under specialist guidance

Interacting Drug Effect/Mechanism Recommendation

Unfractionated heparin Synergistic antiplatelet and anticoagulant effects Expected combination in ACS/PCI; maintain aPTT 50–70 seconds; monitor for bleeding

Low molecular weight heparin (enoxaparin) Additive bleeding risk Can be used with caution; monitor closely

Clopidogrel/Prasugrel/Ticagrelor Additive antiplatelet effect Can be co-administered; enhanced bleeding risk — monitor

Aspirin Additive antiplatelet effect Standard co-administration in ACS; monitor for bleeding

NSAIDs (ibuprofen, diclofenac) Increased bleeding tendency via platelet dysfunction Limit concurrent use; avoid if possible during infusion

SSRIs/SNRIs (fluoxetine, venlafaxine) Enhanced bleeding through serotonin-mediated platelet dysfunction Monitor for bleeding; counsel patient

Cephalosporins with NMTT side chain (cefoperazone, cefotetan) Increased bleeding tendency via vitamin K antagonism Use with caution; monitor coagulation

• Bleeding at vascular access/puncture sites

• Minor bleeding (gingival, epistaxis, ecchymosis)

• Hypotension (particularly during/after bolus)

• Nausea

• Headache

• Back pain

• Mild thrombocytopenia (reversible)

Adverse Effect Clinical Action

Intracranial haemorrhage Discontinue immediately; urgent neuroimaging; neurosurgical consultation

Major gastrointestinal/retroperitoneal bleeding Discontinue infusion; supportive care; transfusion if required

Severe thrombocytopenia (<20,000/mm³) May occur rapidly (within hours); discontinue drug; platelet transfusion may be required

Anaphylaxis/severe hypersensitivity Rare; discontinue immediately; standard anaphylaxis management

Pulmonary haemorrhage Discontinue; supportive respiratory care

Within 2–4 hours of initiation Platelet count (to detect acute thrombocytopenia)

During therapy Daily platelet counts; continuous observation for bleeding at catheter/injection sites; signs of internal bleeding; renal function if prolonged infusion

Post-PCI (18–24 hours) Continue monitoring for delayed bleeding; access site haematoma surveillance

Post-discontinuation Platelet count recovery confirmation if thrombocytopenia occurred

Brand Name Manufacturer Formulations

Integrilin® Merck (MSD) 20 mg/10 mL vial; 75 mg/100 mL infusion bag

Note: No generic formulations widely available in Indian market as of current data.

Regulatory Note: Not included in NLEM; price not controlled by NPPA. Available primarily through hospital procurement channels.

• Triple therapy essential: Always co-administer with aspirin and unfractionated heparin in ACS/PCI — improves outcomes significantly in high-risk patients.

• Mandatory second bolus: For PCI, a second 180 mcg/kg bolus 10 minutes after the first is required for optimal platelet inhibition — do not omit.

• Early platelet monitoring: Check platelet count within 4 hours of starting therapy — acute profound thrombocytopenia can occur unpredictably and requires immediate discontinuation.

• Renal dosing critical: Reduce maintenance infusion to 1 mcg/kg/min if CrCl <50 mL/min; avoid entirely in dialysis patients.

• Sheath management: Avoid femoral sheath removal until aPTT <45 seconds or ACT <150 seconds to minimise access site bleeding.

• No reversal agent: There is no specific antidote; platelet function recovers within 4–8 hours of discontinuation due to short half-life.

eptifibatide; acute coronary syndrome; ACS; PCI; percutaneous coronary intervention; antiplatelet; glycoprotein IIb/IIIa inhibitor; GP IIb/IIIa; bleeding risk; hospital IV agent; Integrilin; thrombocytopenia; NSTEMI; unstable angina

RxIndia v1.0 — 11 Jan 2025

• CDSCO (Central Drugs Standard Control Organisation) — Product labelling information

• Indian Pharmacopoeia

• AIIMS Cardiovascular Treatment Guidelines

• API Textbook of Medicine, 11th Edition

• Hospital protocols — AIIMS New Delhi, PGIMER Chandigarh

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive reference)

• ESC ACS Guidelines (used only as comparative context for international practice alignment)