Eptifibatide

Dosage Forms & Strengths

injection solution

• 2mg/mL
• 0.75mg

Acute Coronary Syndromes

180 mcg/kg IV bolus over 1-2 min, THEN 

2 mcg/kg/min IV for up to 72 hr

Percutaneous Coronary Intervention

180 mcg/kg IV, THEN 

Continuous infusion 2 mcg/kg/min with another 180 mcg/kg IV bolus 10 minutes after 1st one

Continue infusion for at least 12 hours

Renal Impairment

(CrCl <50 mL/min)

ACS: 180 mcg/kg IV, THEN continuous infusion 1 mcg/kg/min 

PCI: 180 mcg/kg IV, THEN continuous infusion 1 mcg/kg/min with another 180 mcg/kg IV bolus 10 minutes after 1st one

Hemodialysis: Safety and using during hemodialysis not established

Safety & efficacy not established

In clinical trials, incidence of bleeding complications was higher in the elderly in both placebo and eptifibatide groups, and the incremental risk of eptifibatide-associated bleeding was greater in the older patients. Adjust dose to renal function

Acute Coronary Syndromes

180 mcg/kg IV bolus over 1-2 min, THEN 

2 mcg/kg/min IV for up to 72 hr

Percutaneous Coronary Intervention

180 mcg/kg IV, THEN

Continuous infusion 2 mcg/kg/min with another 180 mcg/kg IV bolus 10 minutes after 1st one

Continue infusion for at least 12 hours

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

• a light-headed feeling, like you might pass out;
• any bleeding that will not stop;
• bleeding around your IV or catheter, or in any place where your skin has been punctured with a needle;
• red or pink urine; or
• signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds.

The risk of bleeding may be higher in older adults.

Common side effects may include:

• bleeding; or
• feeling lightheaded.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Eptifibatide is injected into a vein through an IV. A healthcare provider will give you this medicine. Eptifibatide is sometimes given around the clock for up to 4 days in a row.

If you are receiving this injection during an angioplasty procedure, the medicine will be given throughout the entire procedure and for up to 24 hours after the procedure.

Eptifibatide is sometimes given together with aspirin. Follow your doctor's instructions about how much aspirin to take and for how long.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often.

Because eptifibatide keeps your blood from coagulating (clotting), this medicine can also make it easier for you to bleed, even from a minor injury. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Since eptifibatide is given by a healthcare professional, you are not likely to miss a dose.

The following serious adverse reaction is also discussed elsewhere in the labeling:

• Bleeding [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 16,782 patients were treated in the Phase III clinical trials (PURSUIT, ESPRIT, and IMPACT II) [see Clinical Trials]. These 16,782 patients had a mean age of 62 years (range: 2094 years). Eighty-nine percent of the patients were Caucasian, with the remainder being predominantly Black (5%) and Hispanic (5%). Sixty-eight percent were men. Because of the different regimens used in PURSUIT, IMPACT II, and ESPRIT, data from the 3 studies were not pooled.

Bleeding and hypotension were the most commonly reported adverse reactions (incidence ≥ 5% and greater than placebo) in the INTEGRILIN controlled clinical trial database.

The incidence of bleeding and transfusions in the PURSUIT and ESPRIT studies are shown in Table 2. Bleeding was classified as major or minor by the criteria of the TIMI study group. Major bleeding consisted of intracranial hemorrhage and other bleeding that led to decreases in hemoglobin greater than 5 g/dL. Minor bleeding included spontaneous gross hematuria, spontaneous hematemesis, other observed blood loss with a hemoglobin decrease of more than 3 g/dL, and other hemoglobin decreases that were greater than 4 g/dL but less than 5 g/dL. In patients who received transfusions, the corresponding loss in hemoglobin was estimated through an adaptation of the method of Landefeld et al.

Table 2: Bleeding and Transfusions in the PURSUIT and ESPRIT Studies

The majority of major bleeding reactions in the ESPRIT study occurred at the vascular access site (1 and 8 patients, or 0.1% and 0.8% in the placebo and INTEGRILIN groups, respectively). Bleeding at “other” locations occurred in 0.2% and 0.4% of patients, respectively.

In the PURSUIT study, the greatest increase in major bleeding in INTEGRILIN-treated patients compared to placebo-treated patients was also associated with bleeding at the femoral artery access site (2.8% versus 1.3%). Oropharyngeal (primarily gingival), genitourinary, gastrointestinal, and retroperitoneal bleeding were also seen more commonly in INTEGRILIN-treated patients compared to placebo-treated patients.

Among patients experiencing a major bleed in the IMPACT II study, an increase in bleeding on INTEGRILIN versus placebo was observed only for the femoral artery access site (3.2% versus 2.8%).

Table 3 displays the incidence of TIMI major bleeding according to the cardiac procedures carried out in the PURSUIT study. The most common bleeding complications were related to cardiac revascularization (CABG-related or femoral artery access site bleeding). A corresponding table for ESPRIT is not presented, as every patient underwent PCI in the ESPRIT study and only 11 patients underwent CABG.

Table 3: Major Bleeding by Procedures in the PURSUIT Study

In the PURSUIT and ESPRIT studies, the risk of major bleeding with INTEGRILIN increased as patient weight decreased. This relationship was most apparent for patients weighing less than 70 kg.

Bleeding resulting in discontinuation of the study drug was more frequent among patients receiving INTEGRILIN than placebo (4.6% versus 0.9% in ESPRIT, 8% versus 1% in PURSUIT, 3.5% versus 1.9% in IMPACT II).

Intracranial hemorrhage was rare in the PURSUIT, IMPACT II, and ESPRIT clinical studies. In the PURSUIT study, 3 patients in the placebo group, 1 patient in the group treated with INTEGRILIN 180/1.3, and 5 patients in the group treated with INTEGRILIN 180/2 experienced a hemorrhagic stroke. The overall incidence of stroke was 0.5% in patients receiving INTEGRILIN 180/1.3, 0.7% in patients receiving INTEGRILIN 180/2, and 0.8% in placebo patients.

In the IMPACT II study, intracranial hemorrhage was experienced by 1 patient treated with INTEGRILIN 135/0.5, 2 patients treated with INTEGRILIN 135/0.75, and 2 patients in the placebo group. The overall incidence of stroke was 0.5% in patients receiving 135/0.5 INTEGRILIN, 0.7% in patients receiving INTEGRILIN 135/0.75, and 0.7% in the placebo group.

In the ESPRIT study, there were 3 hemorrhagic strokes, 1 in the placebo group and 2 in the INTEGRILIN group. In addition there was 1 case of cerebral infarction in the INTEGRILIN group.

The potential for development of antibodies to eptifibatide has been studied in 433 subjects. INTEGRILIN was nonantigenic in 412 patients receiving a single administration of INTEGRILIN (135mcg/kg bolus followed by a continuous infusion of either 0.5 mcg/kg/min or 0.75 mcg/kg/min), and in 21 subjects to whom INTEGRILIN (135-mcg/kg bolus followed by a continuous infusion of 0.75 mcg/kg/min) was administered twice, 28 days apart. In both cases, plasma for antibody detection was collected approximately 30 days after each dose. The development of antibodies to eptifibatide at higher doses has not been evaluated.

In patients with suspected INTEGRILIN-related immune-mediated thrombocytopenia, IgG antibodies that react with the GP IIb/IIIa complex were identified in the presence of eptifibatide and in INTEGRILIN-naïve patients. These findings suggest acute thrombocytopenia after the administration of INTEGRILIN can develop as a result of naturally occurring drug-dependent antibodies or those induced by prior exposure to INTEGRILIN. Similar antibodies were identified with other GP IIb/IIIa ligand-mimetic agents. Immune-mediated thrombocytopenia with INTEGRILIN may be associated with hypotension and/or other signs of hypersensitivity.

In the PURSUIT and IMPACT II studies, the incidence of thrombocytopenia ( < 100,000/mm³ or ≥ 50% reduction from baseline) and the incidence of platelet transfusions were similar between patients treated with INTEGRILIN and placebo. In the ESPRIT study, the incidence was 0.6% in the placebo group and 1.2% in the INTEGRILIN group.

In the PURSUIT and ESPRIT studies, the incidence of serious nonbleeding adverse reactions was similar in patients receiving placebo or INTEGRILIN (19% and 19%, respectively, in PURSUIT; 6% and 7%, respectively, in ESPRIT). In PURSUIT, the only serious nonbleeding adverse reaction that occurred at a rate of at least 1% and was more common with INTEGRILIN than placebo (7% versus 6%) was hypotension. Most of the serious nonbleeding adverse reactions consisted of cardiovascular reactions typical of a UA population. In the IMPACT II study, serious nonbleeding adverse reactions that occurred in greater than 1% of patients were uncommon and similar in incidence between placebo- and INTEGRILIN-treated patients.

Discontinuation of study drug due to adverse reactions other than bleeding was uncommon in the PURSUIT, IMPACT II, and ESPRIT studies, with no single reaction occurring in > 0.5% of the study population (except for “other” in the ESPRIT study).

Postmarketing Experience

Because the reactions below are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported in postmarketing experience, primarily with INTEGRILIN in combination with heparin and aspirin: cerebral, GI, and pulmonary hemorrhage. Fatal bleeding reactions have been reported. Acute profound thrombocytopenia, as well as immune-mediated thrombocytopenia, has been reported.

Since eptifibatide is given by a healthcare professional, you are not likely to miss a dose.

Eptifibatide is injected into a vein through an IV. A healthcare provider will give you this medicine. Eptifibatide is sometimes given around the clock for up to 4 days in a row.

If you are receiving this injection during an angioplasty procedure, the medicine will be given throughout the entire procedure and for up to 24 hours after the procedure.

Eptifibatide is sometimes given together with aspirin. Follow your doctor's instructions about how much aspirin to take and for how long.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often.

Because eptifibatide keeps your blood from coagulating (clotting), this medicine can also make it easier for you to bleed, even from a minor injury. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop.

Usual Adult Dose for Myocardial Infarction:

Initial: 180 mcg/kg intravenous bolus administered as soon as possible following diagnosis
Maintenance: 2 mcg/kg/min continuous infusion (following the initial bolus) until hospital discharge or initiation of CABG surgery, up to 72 hours. If a patient is to undergo a percutaneous coronary intervention (PCI) while receiving eptifibatide, the infusion should be continued up to hospital discharge, or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy.

In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.

Usual Adult Dose for Angina Pectoris:

Initial: 180 mcg/kg intravenous bolus administered as soon as possible following diagnosis
Maintenance: 2 mcg/kg/min continuous infusion (following the initial bolus) until hospital discharge or initiation of CABG surgery, up to 72 hours. If a patient is to undergo a percutaneous coronary intervention (PCI) while receiving eptifibatide, the infusion should be continued up to hospital discharge, or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy.

In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.

Usual Adult Dose for Acute Coronary Syndrome:

Initial: 180 mcg/kg intravenous bolus administered as soon as possible following diagnosis
Maintenance: 2 mcg/kg/min continuous infusion (following the initial bolus) until hospital discharge or initiation of CABG surgery, up to 72 hours. If a patient is to undergo a percutaneous coronary intervention (PCI) while receiving eptifibatide, the infusion should be continued up to hospital discharge, or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy.

In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.

Usual Adult Dose for Percutaneous Coronary Intervention:

Initial: 180 mcg/kg intravenous bolus administered immediately before the initiation of PCI followed by a continuous infusion of 2 mcg/kg/min and a second 180 mcg/kg bolus 10 minutes after the first bolus. Infusion should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of infusion is recommended by the manufacturer. Alternatively, an infusion duration of 16 hours may be appropriate as noted in the ESPRIT substudy.

In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.

Platelet-aggregation inhibitor;1 2 3 10 11 71 a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.2 6 7 11 14 26 37 44 48 50

General

• In patients with NSTE ACS, administer as soon as possible following diagnosis.1 8 72

• Discontinue prior to CABG.1

Adjunctive Antithrombotic Therapy: General Considerations

• Used in conjunction with aspirin and heparin in clinical studies.1 4 8 10 12 13 14 19 40

• Dosage of heparin required to maintain an appropriate activated clotting time (ACT) during concomitant therapy with eptifibatide may be lower than with heparin monotherapy.19 72 113 994 (See Specific Drugs under Interactions.)

• Caution when used in patients requiring thrombolytic therapy.1 (See Specific Drugs under Interactions.)

Adjunctive Antithrombotic Therapy When Used in Management of NSTE ACS

• Aspirin: Manufacturer recommends 160–325 mg initially and daily thereafter.1

• Heparin sodium during medical management: In patients weighing ≥70 kg, 5000 units (IV loading dose) followed by continuous IV infusion of 1000 units/hour.1 In patients weighing <70 kg, 60 units/kg followed by continuous IV infusion of 12 units/kg per hour.1 Adjust dose to maintain a target aPTT of 50–70 seconds.1 (See Laboratory Monitoring under Cautions.)

• Heparin sodium in patients undergoing PCI: Administer multiple IV injections of heparin based on ACT determinations during PCI to achieve and maintain an ACT of ≥200 seconds.1 117 118

Adjunctive Antithrombotic Therapy When Used to Reduce Risk of Acute Ischemic Complications of PCI

• Aspirin: Manufacturer recommends 160–325 mg 1–24 hours prior to PCI and daily thereafter.1 ACCF/AHA/SCAI recommends that aspirin 325 mg be given prior to PCI in patients not already receiving maintenance aspirin therapy.994 Patients already receiving maintenance aspirin therapy should receive a dose of 81–325 mg before the procedure.994

• P2Y12-receptor antagonist: A loading dose of clopidogrel, prasugrel, or ticagrelor also is recommended prior to PCI in patients undergoing stent placement.994 995

• Heparin: 50–70 units/kg 6 hours prior to PCI (target ACT of ≥200 seconds).1 Administer additional injections during PCI to maintain an ACT of 200–300 seconds.1 (See Laboratory Monitoring under Cautions.) Consider a lower dosage of heparin in women and geriatric patients receiving a GP IIb/IIIa-receptor inhibitor to decrease the increased risk of minor bleeding.128 Postprocedural use of heparin not recommended.1 10 26

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV injection followed by IV infusion using a controlled-infusion device (e.g., pump).1

For IV injection, withdraw appropriate dose from the 10-mL vial and administer undiluted.1 71

For continuous IV infusion, spike the 100-mL vial with a vented infusion set; center spike within the circle on stopper top.1 Administer solution directly from vial.1 8 71

Discard unused portion.1

Administer undiluted.1

For IV injection, administer over 1–2 minutes.1 71

Dosage

Adults

180 mcg/kg by IV injection as soon as possible following diagnosis, followed by IV infusion of 2 mcg/kg per minute until hospital discharge or initiation of CABG, or for ≤72 hours.1 8 72

If patient undergoes PCI while receiving eptifibatide, continue infusion (at 2 mcg/kg per minute) until hospital discharge or for ≤18–24 hours after procedure, whichever comes first, up to a maximum of 96 hours.1

180 mcg/kg by IV injection immediately before initiation of PCI, immediately followed by IV infusion of 2 mcg/kg per minute and a second IV injection of 180 mcg/kg 10 minutes after the first IV injection.1 117 118

Continue infusion (at 2 mcg/kg per minute) until hospital discharge or for ≤18–24 hours, whichever comes first.1 A minimum infusion period of 12 hours is recommended.1

Prescribing Limits

Adults

Maximum IV infusion of 72 hours.1 8 72

In patients undergoing PCI, maximum IV infusion of 96 hours.1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.8

Renal Impairment

No dosage adjustment required in patients with mild to moderate renal impairment (Clcr ≥50 mL/minute).1

In patients with Clcr <50 mL/minute, 180 mcg/kg by IV injection as soon as possible following diagnosis, followed by IV infusion of 1 mcg/kg per minute.1

In patients with Clcr <50 mL/minute, 180 mcg/kg by IV injection immediately before initiation of PCI, followed by IV infusion of 1 mcg/kg per minute and a second IV injection of 180 mcg/kg 10 minutes after the first IV injection.1

Geriatric Patients

No dosage adjustment was made for geriatric patients in clinical trials.1 (See Geriatric Use under Cautions.)

• If you need to store eptifibatide at home, talk with your doctor, nurse, or pharmacist about how to store it.

(ep TIF i ba tide)

• Intrifiban

Hypersensitivity to eptifibatide or any component of the formulation; active abnormal bleeding within the previous 30 days or a history of bleeding diathesis; history of stroke within 30 days or a history of hemorrhagic stroke; severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding 6 weeks; current or planned administration of another parenteral GP IIb/IIIa inhibitor; dependency on hemodialysis

Canadian labeling: Additional contraindications (not in U.S. labeling): PT >1.2 times control or INR ≥2.0; known history of intracranial disease (eg, neoplasm, arteriovenous malformation, aneurysm); severe renal impairment ( CrCl <30 mL/minute); thrombocytopenia (<100,000 cells/mm3); clinically significant liver disease

Refer to adult dosing. No dosing adjustment for the elderly appears to be necessary; adjust carefully to renal function.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Acute Coronary Syndrome
CrCl less than 50 mL/min (or serum creatinine greater than 2.0 mg/dL if creatinine clearance is not available): 180 mcg/kg intravenous bolus as soon as possible following diagnosis, immediately followed by a continuous infusion of 1 mcg/kg/min.

Percutaneous Coronary Intervention (PCI)
CrCl less than 50 mL/min (or serum creatinine greater than 2.0 mg/dL if creatinine clearance is not available): 180 mcg/kg intravenous bolus administered immediately before the initiation of the procedure, immediately followed by a continuous infusion of 1 mcg/kg/min and a second 180 mcg/kg bolus administered 10 minutes after the first.

Data not available

There are no data on the excretion of eptifibatide in human milk. Because many drugs are excreted in human milk, caution should be exercised when eptifibatide is administered to a nursing mother.