Skip to content
PeptideAI
Approved drugcardiovascular

Eptifibatide

A snake-venom-derived cyclic peptide drip that blocks the final common step of platelet clumping during heart attacks and stenting.

Also known as Integrilin, barbourin-derived cyclic heptapeptide, KGD peptide, Integrilin, C68-22, SB-1

Approved drug — Licensed by a major regulator for human use, with phase-3 trial data behind it.

FDA-approved on the PURSUIT trial in acute coronary syndrome and the ESPRIT trial in elective stenting, both showing reduced ischaemic events at the cost of more bleeding. Its role has shrunk considerably in the era of potent oral P2Y12 inhibitors, and it is now mostly a bail-out agent for large thrombus burden.

How it works

Eptifibatide is built around the Lys-Gly-Asp (KGD) motif found in barbourin, a disintegrin from the venom of the southeastern pygmy rattlesnake. KGD gives it selectivity for platelet GPIIb/IIIa (integrin alpha-IIb beta-3) over the related vitronectin receptor. By occupying that receptor it prevents fibrinogen and von Willebrand factor from cross-linking activated platelets, which is the final common pathway of aggregation regardless of the upstream trigger. Blockade is reversible and dose-dependent, with platelet function recovering within 4-8 hours of stopping the infusion. Clearance is about 50 percent renal, so the infusion rate is halved in significant kidney impairment.

Targets: Platelet glycoprotein IIb/IIIa receptor (integrin alpha-IIb beta-3)

Dosing

ProtocolDoseFrequencyRoute
Acute coronary syndrome / PCI (label protocol)Bolus at the start of the procedure or on presentation with ACS.—bolus then continuous infusion up to 18-72 hoursintravenous
  • · 180 mcg/kg IV bolus, then 2 mcg/kg/min infusion; in PCI a second 180 mcg/kg bolus is given 10 minutes after the first. Weight-based, so no fixed total microgram dose applies. Infusion is halved to 1 mcg/kg/min when creatinine clearance is under 50 mL/min, and it is contraindicated on dialysis.

Titration

No effect-based titration. The single adjustment that matters is halving the infusion rate for creatinine clearance below 50 mL/min.

Cycling

Procedural only. Infusion runs up to 18 hours after PCI or up to 72 hours in medically managed acute coronary syndrome.

Work out your exact syringe units →

Pharmacology

Half-life
About 2.5 hours; platelet aggregation recovers substantially within 4 hours of stopping.
Onset
More than 80 percent inhibition of platelet aggregation within 15 minutes of the bolus.
Routes
intravenous
Molecule
Cyclic heptapeptide (disulfide-bridged, KGD motif)
Sequence length
7 amino acids
Molecular weight
831.96 Da

Handling

Diluent
Not applicable - supplied as a ready-to-use sterile solution
Lyophilised
Not supplied lyophilised.
Reconstituted
Vials refrigerated at 2-8 C; may be kept at room temperature for up to 2 months, after which they must be discarded.
Light sensitive
Yes — keep it out of the light

Mixing

Supplied as 20 mg/10 mL bolus vials and 75 mg/100 mL infusion vials; nothing is reconstituted.

Side effects

  • very commonBleeding, especially at the femoral access site— The main dose-limiting effect; radial access substantially reduces it.
  • commonHypotension
  • uncommonThrombocytopenia— Can be profound and appear within hours of the first dose; check platelets at baseline, 2-6 hours in, and daily.
  • rareIntracranial haemorrhage
  • rareHypersensitivity reaction

Do not use if

  • Active abnormal bleeding within the previous 30 days or a bleeding diathesis.
  • History of stroke within 30 days, or any history of haemorrhagic stroke.
  • Severe uncontrolled hypertension (systolic above 200 or diastolic above 110 mmHg).
  • Major surgery within the previous 6 weeks.
  • Dependency on renal dialysis - the drug is contraindicated outright.
  • Platelet count below 100,000/mm3.

Combining it

  • cautionbivalirudin — Combining a GPIIb/IIIa blocker with a direct thrombin inhibitor removes the bleeding advantage of bivalirudin alone.
  • cautionheparin — Routinely co-administered during PCI, but heparin dosing is reduced to keep ACT in a lower target range.
  • cautionthrombolytics — Sharply increased haemorrhage risk; combination is generally avoided.

What to monitor

  • · Platelet count at baseline, within 2-6 hours of starting, and at least daily thereafter.
  • · Haemoglobin and haematocrit.
  • · Serum creatinine and creatinine clearance before the bolus.
  • · Vascular access site inspection and neurological checks.

Legal status

FDA- and EMA-approved prescription drug for in-hospital intravenous use.

References

  • Integrilin (eptifibatide) FDA prescribing information (label)
  • PURSUIT Investigators 1998, eptifibatide in acute coronary syndromes (trial)
  • ESPRIT Investigators 2000, eptifibatide for coronary stent implantation (trial)

Mechanism in depth

Eptifibatide is a snake-venom disintegrin reduced to its business end. Most disintegrins present an RGD motif, which binds alphaIIbbeta3 on platelets but also alphavbeta3 on endothelium and osteoclasts. Barbourin instead presents KGD, and that single lysine-for-arginine swap buys selectivity for alphaIIbbeta3, which is why eptifibatide does not carry the off-target vascular effects of the earlier RGD compounds. The cyclic heptapeptide presents a KGD-like surface, with homoarginine standing in for lysine, to the fibrinogen-binding pocket of activated GPIIb/IIIa. Blocking that receptor blocks the final common pathway of platelet aggregation: no matter which agonist activated the platelet, thrombin, ADP, thromboxane or collagen, aggregation requires fibrinogen and von Willebrand factor bridging adjacent GPIIb/IIIa receptors, and eptifibatide prevents that bridging. Binding is competitive, low-affinity and rapidly reversible, in contrast to abciximab, which is an antibody fragment with slow dissociation. That reversibility is the clinically useful property: greater than 80 percent inhibition of platelet aggregation during infusion, substantial recovery within about 4 hours of stopping, and platelet function largely restored before most patients go to surgery.

What usually goes wrong

Bleeding at the access site is the routine problem. Acute profound thrombocytopenia is the dramatic one, and it can appear within two to six hours of first exposure with counts below 20,000; it is immune-mediated, reversible on stopping, and responds to platelet transfusion because the drug is low-affinity and redistributes. Renal impairment doubles exposure, and the specific error is halving the bolus along with the infusion, which under-treats the patient during the highest-risk minutes. Dialysis-dependent patients should not receive it at all.

Bloodwork worth running

MarkerWhenWhy it matters
Platelet countBaseline, then 2 to 6 hours after starting the infusion, then at least daily.Acute profound thrombocytopenia, meaning a count under 20,000 per microlitre within hours of the first exposure, is the signature toxicity of the GPIIb/IIIa class. It is immune-mediated against a drug-induced conformational epitope, it can be dramatic, and it is missed if nobody checks.Act if: A count below 100,000 or a fall of more than 50 percent from baseline means stop the infusion. Below 20,000 with bleeding means platelet transfusion, which works because the drug dissociates rapidly onto transfused platelets.
Creatinine clearanceBaseline, before the bolus.Half of total clearance is renal and levels double below CrCl 50 mL/min. The bolus does not need adjustment because it sets the initial concentration independent of clearance; the infusion does.Act if: CrCl at or below 50 mL/min: halve the infusion to 1.0 mcg/kg/min. Dialysis dependence is a contraindication in the label.
Haemoglobin and haematocritBaseline and 6 to 12 hours in.Bleeding is the dose-limiting toxicity and access-site bleeding is the commonest form.Act if: A fall of 3 g/dL or more, or any need for transfusion, stops the infusion.
Activated clotting timeDuring PCI.Not a measure of eptifibatide effect, but the concomitant heparin dose has to be lowered when a GPIIb/IIIa inhibitor is on board, and ACT is how that is managed.Act if: Target ACT of about 200 to 300 seconds with concomitant heparin rather than the higher targets used without a GPIIb/IIIa inhibitor.

Pharmacokinetics

Bioavailability
100%
Protein binding
25%
Time to steady state
0.25 days
Crosses blood-brain barrier
no
Accumulates
Yes — doses stack before steady state
Metabolism
Minimal. No major metabolites are detectable in human plasma; the drug is excreted largely as parent plus deaminated eptifibatide and more polar fragments.
Elimination
Renal, about 50 percent of total clearance, with the remainder non-renal. Because protein binding is low, eptifibatide is dialysable.

Receptor targets

  • Platelet integrin alphaIIbbeta3 (glycoprotein IIb/IIIa)

    Competitive, reversible blockade of the fibrinogen and von Willebrand factor binding site. Greater than 80 percent inhibition of ex vivo platelet aggregation at therapeutic infusion rates, with recovery within about 4 hours of stopping.

  • Integrin alphavbeta3 (vitronectin receptor)

    Largely spared, because the KGD motif inherited from barbourin discriminates against it. This is the design rationale for the molecule.

Trials

  • PURSUIT Phase 3 · n=10948 · 4.3 weeks · 1998

    Death or non-fatal myocardial infarction at 30 days in non-ST-elevation acute coronary syndrome. Absolute reduction of 1.5 percentage points (14.2 versus 15.7 percent, p=0.04), with more bleeding but no excess haemorrhagic stroke.

  • ESPRIT Phase 3 · n=2064 · 4.3 weeks · 2000

    Composite of death, MI, urgent target vessel revascularisation and thrombotic bailout within 48 hours of elective coronary stenting, using a novel double 180 mcg/kg bolus plus 2.0 mcg/kg/min infusion. Positive, and the source of the modern dosing scheme.

What to expect, and when

Greater than 80 percent inhibition of platelet aggregation within about 15 minutes of the bolus. Steady state at 4 to 6 hours with a single bolus, or immediately with the double-bolus scheme. Platelet aggregation recovers substantially within 4 hours of stopping and is essentially normal by 8 hours in normal renal function.

Stacking and comparisons

Eptifibatide is layered on top of aspirin, a P2Y12 inhibitor and heparin, and the heparin dose must come down when it is added, targeting a lower ACT than heparin alone. Adding it to bivalirudin is exactly the combination bivalirudin was designed to replace, and doing it routinely erases bivalirudin's bleeding advantage; as bail-out for a large thrombus burden or no-reflow it is still defensible. Stacking with thrombolytics is a haemorrhagic-stroke generator and is not done. In the era of ticagrelor, prasugrel and cangrelor, most of the antiplatelet effect eptifibatide used to supply is already present before the patient reaches the table, which is the real reason its use has collapsed.

Against abciximab: eptifibatide is small, reversible and renally cleared, abciximab is an antibody fragment with slow platelet dissociation and a much longer functional effect; if a patient needs urgent surgery, eptifibatide is the more forgiving choice. Against tirofiban: broadly interchangeable, both small-molecule reversible blockers with renal clearance. Against modern oral P2Y12 inhibitors: the incremental benefit of adding a GPIIb/IIIa inhibitor to potent oral therapy is small and the bleeding cost is real, which is why it has become a bail-out drug rather than a routine one.

Rough cost

Hospital-administered infusion priced per case, not per month. Generic since the mid-2010s; typical courses run 18 to 24 hours.

Genuinely uncertain

  • Volume of distribution is not stated in the label and I did not resolve a primary source, so it is null.
  • The receptor affinity of eptifibatide for alphaIIbbeta3 is often quoted in the low nanomolar range but I did not verify a specific Kd or IC50 in this session.
  • The precise incidence of acute profound thrombocytopenia with eptifibatide, usually quoted below 1 percent, was not verified against a primary source here.

Papers