Integrilin
Integrilin (Eptifibatide) side effects drug center
Integrilin Side Effects Center
What Is Integrilin?
Integrilin (eptifibatide) injection is a platelet aggregation inhibitor indicated for treatment of acute coronary syndrome (ACS) managed medically or with percutaneous coronary intervention (PCI), and treatment of patients undergoing PCI (including intracoronary stenting). Integrilin injection is available in generic form.
What Are Side Effects of Integrilin?
Common side effects of Integrilin injection include:
- bleeding
- low blood pressure
Tell your doctor if you have serious side effects of Integrilin injection including:
- easy bruising,
- unusual bleeding (nose, mouth, vagina, or rectum),
- purple or red pinpoint spots under your skin
- blood in your urine
- black, bloody, or tarry stools
- coughing up blood or vomit that looks like coffee grounds
- any bleeding that will not stop
- sudden numbness or weakness, especially on one side of the body
- sudden severe headache, confusion, problems with vision, speech, or balance
- fever, chills, body aches, flu symptoms, or
- feeling like you might pass out.
Dosage for Integrilin
The dose of Integrilin (eptifibatide) injection to treat ACS or PCI is 180 mcg/kg IV bolus as soon as possible after diagnosis followed by infusion at 2 mcg/kg/min. For PCI, add a second 180 mcg/kg bolus at 10 minutes.
What Drugs, Substances, or Supplements Interact with Integrilin?
Integrilin (eptifibatide) injection may interact with antiplatelet agents, thrombolytics, heparin, aspirin, chronic nonsteridal anti-inflammatory (NSAID) use, and other glycoprotein (GP) IIb/IIIa inhibitors. Tell your doctor all medications and supplements you use.
Integrilin During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Integrilin (eptifibatide) injection; it is unknown how it may affect a fetus. It is unknown if Integrilin (eptifibatide) passes into breast milk. Consult your doctor before breastfeeding.
Additional Information
Our Integrilin (eptifibatide) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Integrilin Consumer Information
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.
Read the entire detailed patient monograph for Integrilin (Eptifibatide)
Integrilin Professional Information
SIDE EFFECTS
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 Studies]. These 16,782 patients had a mean age of 62 years (range: 20-94 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.
Bleeding
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
| PURSUIT (ACS) Placebo n (%) |
INTEGRILIN 180/2 n (%) |
|
| Patients | 4696 | 4679 |
| Major bleeding* | 425 (9.3%) | 498 (10.8%) |
| Minor bleeding* | 347 (7.6%) | 604 (13.1%) |
| Requiring transfusions† | 490 (10.4%) | 601 (12.8%) |
| ESPRIT (PCI) Placebo n (%) |
INTEGRILIN 180/2/180 n (%) |
|
| Patients | 1024 | 1040 |
| Major bleeding* | 4 (0.4%) | 13 (1.3%) |
| Minor bleeding* | 18 (2%) | 29 (3%) |
| Requiring transfusions† | 11 (1.1%) | 16 (1.5%) |
| Note: Denominator is based on patients for whom data are available. * For major and minor bleeding, patients are counted only once according to the most severe classification. † Includes transfusions of whole blood, packed red blood cells, fresh frozen plasma, cryoprecipitate, platelets, and autotransfusion during the initial hospitalization. |
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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
| Placebo n (%) |
INTEGRILIN 180/2 n (%) |
|
| Patients | 4577 | 4604 |
| Overall incidence of major bleeding | 425 (9.3%) | 498 (10.8%) |
| Breakdown by procedure: | ||
| CABG | 375 (8.2%) | 377 (8.2%) |
| Angioplasty without CABG | 27 (0.6%) | 64 (1.4%) |
| Angiography without angioplasty or CABG | 11 (0.2%) | 29 (0.6%) |
| Medical therapy only | 12 (0.3%) | 28 (0.6%) |
| Note: Denominators are based on the total number of patients whose TIMI classification was resolved. | ||
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 And Stroke
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.
Immunogenicity/Thrombocytopenia
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 (135-mcg/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.
Other Adverse Reactions
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
The following adverse reactions have been reported in post-approval use of INTEGRILIN in combination with heparin and aspirin. 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: cerebral, GI, and pulmonary hemorrhage. Fatal bleeding reactions have been reported. Acute profound thrombocytopenia, as well as immune-mediated thrombocytopenia, have been reported [see ADVERSE REACTIONS].
DRUG INTERACTIONS
Use Of Thrombolytics, Anticoagulants, And Other Antiplatelet Agents
Coadministration of antiplatelet agents, thrombolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. Concomitant treatment with other inhibitors of platelet receptor GP IIb/IIIa should be avoided.
Read the entire FDA prescribing information for Integrilin (Eptifibatide)
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