Peptide education
Eptifibatide
Integrilin
Eptifibatide is an intravenous antiplatelet medicine used in certain acute coronary syndromes and during percutaneous coronary intervention, or PCI. It reduces the ability of platelets to stick together by blocking a receptor on their surface.
In the PURSUIT trial, the combined outcome of death or nonfatal heart attack at 30 days occurred in 14.2% of patients assigned to the principal eptifibatide dose and 15.7% assigned to placebo, alongside standard treatment. Bleeding increased with eptifibatide.
Overview
Quick answer
The US label has separate contexts for unstable angina or non-ST-elevation heart attack and for PCI, including stenting. The PCI regimen includes a second bolus that is not part of the initial ACS regimen.
What does eptifibatide do?
It reversibly blocks platelet glycoprotein IIb/IIIa. This interferes with fibrinogen and other adhesive proteins that help activated platelets bind to each other.
When is it used?
The label covers unstable angina and non-ST-elevation myocardial infarction, including patients treated medically or with PCI. It also covers patients undergoing PCI, including coronary stenting.
Are ACS and PCI doses the same?
Both labeled regimens use a weight-based intravenous bolus and infusion. For PCI, the label specifies a second bolus 10 minutes after the first. It also specifies a lower infusion rate below a creatinine clearance of 50 mL/min.
Can someone on dialysis receive it?
Dialysis dependence is a contraindication in the cited US label. It is different from reduced kidney function that calls for a lower infusion rate.
What are the main safety issues?
Bleeding and thrombocytopenia, a low platelet count, are central concerns. The label also lists recent abnormal bleeding, certain stroke histories, severe uncontrolled hypertension, and dialysis dependence among its contraindications.
Evidence
Evidence snapshot
The label specifies unstable angina or non-ST-elevation myocardial infarction and a separate indication for PCI, including intracoronary stenting.
In the principal dose comparison of an acute coronary syndrome trial, the composite was 14.2% with eptifibatide and 15.7% with placebo; both groups received standard care. This does not show that mortality alone fell by that amount.
In planned coronary stenting, a 48-hour composite of death, myocardial infarction, urgent target-vessel treatment, or thrombotic bailout therapy was 6.6% with eptifibatide versus 10.5% with placebo. Major bleeding was 1.3% versus 0.4%.
The label reduces the infusion rate when creatinine clearance is below 50 mL/min and lists dialysis dependence as a contraindication.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Eptifibatide is used for acute coronary syndrome and PCI. | The US indication identifies unstable angina or non-ST-elevation myocardial infarction and also PCI, including stenting. PURSUIT and ESPRIT studied different populations within these coronary-care settings. | Blocking platelet GP IIb/IIIa interferes with platelet aggregation. | The label covers unstable angina, non-ST-elevation heart attack, and PCI, including stenting. |
| Eptifibatide reduces death by 1.5 percentage points. | PURSUIT reported a 1.5 percentage-point difference in a composite of death or nonfatal myocardial infarction, not death alone. The label reports the individual components separately. | Incorrect as stated. A composite result cannot be presented as the same-sized reduction in mortality alone. | |
| Eptifibatide can be used without concern in kidney disease. | The label describes increased exposure with reduced clearance, a lower infusion rate below 50 mL/min, and a contraindication for dialysis-dependent patients. | Not supported. Kidney function changes the labeled infusion and may rule out use. | |
| Reversible platelet inhibition means there is little bleeding risk. | Bleeding is a major label warning. In ESPRIT, major bleeding was 1.3% with eptifibatide and 0.4% with placebo. | Platelet inhibition reverses after the infusion stops, but reversibility does not prevent a serious bleed during treatment. | Not supported. Reversibility and bleeding risk are different safety questions. |
Bottom line
Main takeaway
This medicine helps prevent platelets from sticking together during specific coronary emergencies or procedures. It is given by a medical team and can cause serious bleeding.
ACS and PCI have separate label instructions. Kidney function, platelet count, recent bleeding, and other blood-thinning medicines affect the risk assessment.
PURSUIT assessed death or nonfatal myocardial infarction; ESPRIT used a broader early composite that included urgent intervention and thrombotic bailout therapy.
Identity
What it is
Eptifibatide is a synthetic cyclic heptapeptide containing six amino acids and one mercaptopropionyl residue. It is a platelet aggregation inhibitor administered by the intravenous route.
The label covers unstable angina and non-ST-elevation myocardial infarction, whether managed medically or with PCI, and a separate PCI indication that includes stent placement.
Use context
Routes, doses, and cycle patterns
The US label specifies separate intravenous regimens for ACS and PCI. Both use a bolus and infusion; PCI adds a second bolus, and kidney function affects the infusion rate.
Human studies and product labels
US label, acute coronary syndrome
- Purpose
- Unstable angina or non-ST-elevation myocardial infarction
- Context
- US prescribing information; normal kidney function
- Route
- Intravenous
- Amount
- 180 mcg/kg bolus followed by 2 mcg/kg/min infusion
- Frequency
- Bolus as soon as possible after diagnosis, followed by continuous infusion
- Duration
- Until hospital discharge or start of bypass surgery, up to 72 hours
If PCI follows, the label describes continuation until discharge or up to 18 to 24 hours after PCI, whichever comes first, allowing up to 96 hours total. It also describes aspirin and heparin use and laboratory monitoring.
US label, PCI
- Purpose
- PCI, including intracoronary stenting
- Context
- US prescribing information; normal kidney function
- Route
- Intravenous
- Amount
- 180 mcg/kg bolus followed by 2 mcg/kg/min infusion and a second 180 mcg/kg bolus
- Frequency
- Second bolus 10 minutes after the first; continuous infusion
- Duration
- Until discharge or up to 18 to 24 hours, whichever comes first; label recommends at least 12 hours
The first bolus is given immediately before PCI. The label describes concomitant aspirin and heparin and specifies stopping the infusion before bypass surgery.
US label, reduced kidney function
- Purpose
- ACS or PCI in eligible patients with reduced creatinine clearance
- Context
- US prescribing information
- Route
- Intravenous
- Amount
- Bolus remains 180 mcg/kg; infusion is reduced to 1 mcg/kg/min
- Frequency
- Continuous infusion when creatinine clearance is below 50 mL/min
- Duration
- Depends on the ACS or PCI setting
The label gives a second bolus for PCI and separately contraindicates eptifibatide in patients dependent on dialysis.
PURSUIT
- Purpose
- Acute coronary syndrome without persistent ST elevation
- Context
- Randomized double-blind placebo-controlled trial
- Route
- Intravenous
- Amount
- 180 mcg/kg bolus followed by 2 mcg/kg/min infusion in the principal labeled comparison
- Frequency
- Continuous infusion alongside standard therapy
- Duration
- Up to 72 hours, or up to 96 hours if intervention occurred near the end of that period
The label reports the principal 180/2 comparison; the original trial also enrolled a lower-dose group that was stopped early. The outcome was a composite of death or nonfatal myocardial infarction.
ESPRIT
- Purpose
- Planned native coronary artery stenting
- Context
- Randomized placebo-controlled trial
- Route
- Intravenous
- Amount
- Two 180 mcg/kg boluses 10 minutes apart and a 2 mcg/kg/min infusion; 1 mcg/kg/min if serum creatinine exceeded 2 mg/dL
- Frequency
- Continuous infusion after the first bolus
- Duration
- 18 to 24 hours in the trial protocol
Background care included aspirin, heparin, and a thienopyridine. The trial stopped early for efficacy and reported more major bleeding with eptifibatide. Its serum-creatinine adjustment is not the same rule as the current label's creatinine-clearance threshold.
What varies
- ACS and PCI regimens differ, including the second PCI bolus.
- Creatinine clearance below 50 mL/min changes the labeled infusion rate; dialysis dependence is a contraindication.
- The label calls for platelet count, hemoglobin or hematocrit, creatinine, and coagulation testing before infusion.
- Other antithrombotic medicines and the planned procedure affect bleeding risk and monitoring.
Research
Research evidence
PURSUIT tested eptifibatide in acute coronary syndromes without persistent ST-segment elevation. ESPRIT tested a double-bolus regimen for planned stenting. Both used background treatment, and neither supports treating the composite outcome as a result for death alone.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| PURSUIT | 10,948 patients with acute coronary syndrome without persistent ST elevation | Randomized double-blind placebo-controlled trial | Eptifibatide or placebo added to standard therapy | In the principal 180/2 dose comparison, death or nonfatal myocardial infarction by 30 days was reported in 14.2% of the eptifibatide group versus 15.7% of the placebo group. | The result is for a composite endpoint and the studied background care. Bleeding increased; it does not prove a matching reduction in death alone. | Strong for the studied population |
| ESPRIT | 2,064 patients undergoing planned native coronary artery stenting | Randomized placebo-controlled trial, stopped early for efficacy | Double-bolus eptifibatide and infusion versus placebo, with aspirin, heparin, and a thienopyridine | The 48-hour composite of death, myocardial infarction, urgent target-vessel revascularization, or thrombotic bailout was 6.6% versus 10.5%. Major bleeding was 1.3% versus 0.4%. | The study used its own procedural and background antithrombotic practices and stopped early. The composite included a bailout treatment decision. | Strong for the studied strategy |
Use context
Reported use context
PURSUIT studied eptifibatide in acute coronary syndrome; ESPRIT studied a double-bolus regimen during planned coronary stenting.
Study and label context
180 mcg/kg bolus followed by 2 mcg/kg/min infusion for up to 72 hours, with extension to 96 hours in the specified intervention setting.
Two 180 mcg/kg boluses 10 minutes apart plus 2 mcg/kg/min infusion for 18 to 24 hours; 1 mcg/kg/min if serum creatinine exceeded 2 mg/dL.
Cautions
Safety and unknowns
- Bleeding can be serious, including at arterial access sites and in the gastrointestinal or genitourinary tract. Other anticoagulant or antiplatelet medicines can add to bleeding risk.
- The label warns about thrombocytopenia and calls for platelet monitoring. It directs stopping eptifibatide and heparin for acute profound thrombocytopenia or a confirmed platelet count below 100,000 per microliter.
- The cited label contraindicates dialysis dependence, certain recent bleeding or strokes, severe uncontrolled hypertension, recent major surgery, another parenteral GP IIb/IIIa inhibitor, and product hypersensitivity.
- Kidney impairment increases exposure. Below a creatinine clearance of 50 mL/min, the label lowers the infusion rate; this does not override the dialysis contraindication.
Product quality
Product identity and quality
The cited US product label lists separate intravenous concentrations for bolus and infusion, with handling and storage instructions.
FDA does not approve compounded drugs or review their quality, safety, and effectiveness before marketing. A shared ingredient name does not establish equivalent identity or sterility.
Bolus and infusion products
The cited label specifies different concentrations for bolus and infusion.
Kidney function and blood counts
These affect eligibility, monitoring, and the infusion rate.
Other products
The ingredient name alone does not establish an equivalent sterile injection.
Mechanism
How it is proposed to work
Eptifibatide temporarily blocks a platelet receptor needed for fibrinogen and other adhesive proteins to connect platelets to each other.
The target is glycoprotein IIb/IIIa. Blocking its interaction with fibrinogen, von Willebrand factor, and other ligands inhibits platelet aggregation.
Inhibition is reversible after the infusion ends. Reduced renal clearance can raise exposure, which is why the label specifies a lower infusion rate below its creatinine-clearance threshold.
FAQ
Common questions
Did PURSUIT show a 1.5 percentage-point reduction in death alone?
No. The reported 1.5 percentage-point difference was for the composite of death or nonfatal myocardial infarction, not mortality alone.
Can eptifibatide be used in patients dependent on dialysis?
The cited US label lists dialysis dependence as a contraindication. For creatinine clearance below 50 mL/min in patients not dependent on dialysis, it specifies a lower infusion rate.
Details
Technical details
Sources
References
- 1.
DailyMed. Eptifibatide injection prescribing information
US indications, separate ACS and PCI regimens, renal restrictions, and safety warnings.
- 2.
doi:10.1056/NEJM199808133390704 PMID:9705684
PURSUIT randomized patients with non-ST-elevation acute coronary syndromes to eptifibatide or placebo alongside standard therapy.
- 3.
doi:10.1016/S0140-6736(00)03400-0 PMID:11145489
ESPRIT tested a double-bolus regimen during planned coronary stenting.
- 4.
doi:10.1001/jama.285.19.2468 PMID:11368699
ESPRIT follow-up reports the trial's infusion adjustment for elevated serum creatinine.
- 5.
FDA. Compounding and the FDA: Questions and Answers
FDA describes the approval and premarket review limits for compounded drugs.