Glycoprotein platelet inhibitors

Generic and Brand Names

• Abciximab — ReoPro

• Eptifibatide — Integrilin

• Tirofiban — Aggrastat

Class

• Intravenous antiplatelet agents targeting the platelet glycoprotein IIb/IIIa (αIIbβ3) receptor

• Final-common-pathway inhibitors of platelet aggregation

Mechanism of Action

• Block fibrinogen and von Willebrand factor binding to GPIIb/IIIa → prevent platelet cross-linking and aggregation

• Abciximab: Chimeric monoclonal antibody Fab fragment; noncompetitive receptor blockade; additional binding to vitronectin receptor

• Eptifibatide: Reversible, competitive cyclic heptapeptide (RGD-mimetic)

• Tirofiban: Reversible, competitive non-peptide (RGD-mimetic)

Indications

• Adjunct to percutaneous coronary intervention (PCI) in selected high-risk patients to reduce ischemic complications

• Medical management of high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS) when ischemia persists despite optimal therapy or when PCI is planned and high thrombus burden is anticipated

• Contemporary practice: selective rather than routine use; preference often for potent oral P2Y12 inhibitors with parenteral anticoagulants, reserving GPI for bail-out/high-thrombus scenarios

Dosage and Administration

• Abciximab: IV bolus 0.25 mg/kg immediately before PCI, then infusion 0.125 mcg/kg/min (max 10 mcg/min) for 12 hours (often 12–18 h)

• Eptifibatide: IV bolus 180 mcg/kg ×1, repeat same bolus in 10 minutes; infusion 2 mcg/kg/min for up to 18–24 hours; reduce to 1 mcg/kg/min if CrCl <50 mL/min

• Tirofiban: High-dose bolus 25 mcg/kg over 3 minutes, then infusion 0.15 mcg/kg/min up to 18 hours; reduce to 0.075 mcg/kg/min if CrCl ≤60 mL/min

• Heparin/other anticoagulants are typically co-administered per PCI protocol; adjust UFH dosing and monitor ACT during PCI

Monitoring

• Platelet count at baseline, 2–4 hours after initiation, and at ~24 hours (screen for acute profound thrombocytopenia)

• Hemoglobin/hematocrit and clinical surveillance for bleeding (access site, GI, retroperitoneal, intracranial)

• Activated clotting time (ACT) intra-procedure when UFH used

• Renal function for eptifibatide/tirofiban dosing and ongoing clearance

Contraindications

• Active internal bleeding or history of hemorrhagic stroke

• Intracranial neoplasm/arteriovenous malformation/aneurysm

• Ischemic stroke within 30 days (or any stroke within 2 years for abciximab per many labels)

• Severe uncontrolled hypertension

• Thrombocytopenia (platelets <100,000/µL)

• Major surgery or severe trauma within 4–6 weeks; recent head/spinal surgery or trauma

• Known hypersensitivity to the agent or murine proteins (abciximab)

Precautions

• Higher bleeding risk with concomitant thrombolytics, anticoagulants, other antiplatelets

• Immunogenicity with abciximab (human anti-chimeric antibodies); potential for allergic reactions and more pronounced thrombocytopenia on re-exposure

• Access-site management (radial access preferred when feasible)

• Careful sheath removal and post-PCI hemostasis protocols to minimize bleeding

• Pregnancy/lactation: limited human data; use only if benefit outweighs risk

Adverse Effects

• Bleeding (most common): access-site, GI, retroperitoneal, intracranial (rare)

• Thrombocytopenia: can be sudden and profound, especially with abciximab; immune-mediated forms reported

• Hypotension, bradycardia, nausea, vomiting

• Allergic/infusion reactions (flushing, dyspnea, rash), particularly with abciximab

Drug Interactions

• Additive bleeding with UFH, LMWH, bivalirudin, fondaparinux, thrombolytics, warfarin, DOACs, NSAIDs, and other antiplatelets (aspirin, P2Y12 inhibitors)

• No significant CYP-mediated interactions (parenteral biologic/peptidic agents), but pharmacodynamic interactions dominate

Overdose and Reversal

• Stop infusion; manage bleeding supportively

• Platelet transfusion: most effective for abciximab (long receptor occupancy); less effective for eptifibatide/tirofiban while drug remains in circulation

• Hemodialysis: may remove some tirofiban/eptifibatide due to renal clearance; not useful for abciximab

Patient Counselling

• Purpose is short-term platelet inhibition during/around PCI or high-risk ACS

• Expect close monitoring, frequent blood tests, and access-site care

• Report any bleeding, new bruising, severe headache, weakness, or dizziness immediately

Comparison Table — Abciximab vs Eptifibatide vs Tirofiban

Feature	Abciximab (ReoPro)	Eptifibatide (Integrilin)	Tirofiban (Aggrastat)
Molecular type	Monoclonal antibody Fab (chimeric)	Cyclic heptapeptide (RGD-mimetic)	Non-peptide small molecule (RGD-mimetic)
Binding	Noncompetitive, strong receptor occupancy; also binds vitronectin receptor	Competitive, reversible	Competitive, reversible
Onset	Immediate after bolus	Minutes after bolus	Minutes after bolus
Offset/platelet function recovery	Slow (12–48 h after stop; persistent binding)	Faster (≈4–8 h)	Faster (≈4–8 h)
Plasma half-life	~30 min (effect persists due to receptor binding)	2–3 h	~2 h
Elimination	Reticuloendothelial system	Renal (dose reduce CrCl <50)	Renal (dose reduce CrCl ≤60)
Typical dosing	0.25 mg/kg IV bolus → 0.125 mcg/kg/min (max 10 mcg/min) × 12 h	180 mcg/kg bolus ×2 (10 min apart) → 2 mcg/kg/min × 18–24 h (1 mcg/kg/min if CrCl <50)	25 mcg/kg 3-min bolus → 0.15 mcg/kg/min × up to 18 h (0.075 mcg/kg/min if CrCl ≤60)
Primary use	PCI adjunct in high-risk/large thrombus burden	PCI adjunct; NSTE-ACS with planned early PCI	PCI adjunct; NSTE-ACS with planned early PCI
Thrombocytopenia risk	Higher; abrupt profound cases more frequent	Lower than abciximab	Lower than abciximab
Immunogenicity	Yes (HACA formation); caution on re-exposure	Minimal	Minimal
Dialyzable	No	Partial	Partial
Practical pearls	Powerful, but bleeding/thrombocytopenia risk; platelet transfusion reverses effect best	Renal dosing crucial; shorter offset aids post-PCI hemostasis	Renal dosing crucial; commonly used high-dose bolus strategy before PCI