Integrilin

Serious side effects have been reported with Integrilin. See the "Drug Precautions" section.

Common side effects of Integrilin include bleeding and decreased blood pressure.

This is not a complete list of Integrilin side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors).1 2 3 4 7 8 16 37 71

• Modest effect on hemostatic indices (e.g., bleeding times) and platelet function; normal hemostasis restored more rapidly than with abciximab.1 2 6 10 17 72

• Usually does not affect PT or aPTT when administered as monotherapy.1

It is very important that your doctor check you at regular visits after you leave the hospital for any problems or unwanted effects that may be caused by this medicine. Be sure to keep all appointments.

You may bleed and bruise more easily while you are using this medicine. Be extra careful to avoid injuries until the effects of the medicine have worn off. For some patients, this may take about 2 or 3 days. For other patients, it may take longer. Talk with your doctor about this.

Check with your doctor right away if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin. Avoid picking your nose. If you need to blow your nose, blow it gently.

You may be told to use a soft toothbrush or to shave with an electric razor (not a razor blade) for a few days after you have been given this medicine. This helps reduce the risk of bleeding.

Watch for any bleeding from open areas such as sites of needle punctures for drawing blood, giving shots, or putting in a catheter for a heart catheterization or angioplasty. Also check for blood in your urine or bowel movements. If you have any bleeding or injuries, tell your doctor right away.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• If you have an allergy to eptifibatide or any other part of Integrilin (eptifibatide).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have bleeding problems.
• If you have had any of these health problems: Bleeding in the brain, active bleeding or stroke within the past 30 days, or surgery within the past 6 weeks.
• If you have high blood pressure.
• If you have kidney disease or are on dialysis.
• If you are taking or will be taking another drug like this one.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Integrilin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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

Acute Coronary Syndrome (ACS)

Integrilin® is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction (MI) in patients with ACS (unstable angina [UA]/non-ST-elevation myocardial infarction [NSTEMI]), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI).

Percutaneous Coronary Intervention (PCI)

Integrilin is indicated to decrease the rate of a combined endpoint of death, new MI, or need for urgent intervention in patients undergoing PCI, including those undergoing intracoronary stenting [see Clinical Studies (14.1, 14.2)].

Bleeding

Bleeding is the most common complication encountered during Integrilin therapy. Administration of Integrilin is associated with an increase in major and minor bleeding, as classified by the criteria of the Thrombolysis in Myocardial Infarction Study group (TIMI) [see Adverse Reactions (6.1)]. Most major bleeding associated with Integrilin has been at the arterial access site for cardiac catheterization or from the gastrointestinal or genitourinary tract. Minimize the use of arterial and venous punctures, intramuscular injections, and the use of urinary catheters, nasotracheal intubation, and nasogastric tubes. When obtaining intravenous access, avoid non-compressible sites (e.g., subclavian or jugular veins).

Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents

Risk factors for bleeding include older age, a history of bleeding disorders, and concomitant use of drugs that increase the risk of bleeding (thrombolytics, oral anticoagulants, nonsteroidal anti-inflammatory drugs, and P2Y12 inhibitors). Concomitant treatment with other inhibitors of platelet receptor glycoprotein (GP) IIb/IIIa should be avoided. In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT and ACT [see Dosage and Administration (2)].

Care of the Femoral Artery Access Site in Patients Undergoing Percutaneous Coronary Intervention (PCI)

In patients undergoing PCI, treatment with Integrilin is associated with an increase in major and minor bleeding at the site of arterial sheath placement. After PCI, Integrilin infusion should be continued until hospital discharge or up to 18 to 24 hours, whichever comes first. Heparin use is discouraged after the PCI procedure. Early sheath removal is encouraged while Integrilin is being infused. Prior to removing the sheath, it is recommended that heparin be discontinued for 3 to 4 hours and an aPTT of <45 seconds or ACT <150 seconds be achieved. In any case, both heparin and Integrilin should be discontinued and sheath hemostasis should be achieved at least 2 to 4 hours before hospital discharge. If bleeding at access site cannot be controlled with pressure, infusion of Integrilin and heparin should be discontinued immediately.

Thrombocytopenia

There have been reports of acute, profound thrombocytopenia (immune-mediated and non-immune mediated) with Integrilin. In the event of acute profound thrombocytopenia or a confirmed platelet decrease to <100,000/mm3, discontinue Integrilin and heparin (unfractionated or low-molecular weight). Monitor serial platelet counts, assess the presence of drug-dependent antibodies, and treat as appropriate [see Adverse Reactions (6.1)].

There has been no clinical experience with Integrilin initiated in patients with a baseline platelet count <100,000/mm3. If a patient with low platelet counts is receiving Integrilin, their platelet count should be monitored closely.

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

• Bleeding [see Contraindications (4) and Warnings and Precautions (5.1)]

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 (14)]. 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.

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.

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

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 [see Adverse Reactions (6.1)].

Pregnancy

Pregnancy Category B

Teratology studies have been performed by continuous intravenous infusion of eptifibatide in pregnant rats at total daily doses of up to 72 mg/kg/day (about 4 times the recommended maximum daily human dose on a body surface area basis) and in pregnant rabbits at total daily doses of up to 36 mg/kg/day (also about 4 times the recommended maximum daily human dose on a body surface area basis). These studies revealed no evidence of harm to the fetus due to eptifibatide. There are, however, no adequate and well-controlled studies in pregnant women with Integrilin. Because animal reproduction studies are not always predictive of human response, Integrilin should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether eptifibatide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Integrilin is administered to a nursing mother.

Pediatric Use

Safety and effectiveness of Integrilin in pediatric patients have not been studied.

Geriatric Use

The PURSUIT and IMPACT II clinical studies enrolled patients up to the age of 94 years (45% were age 65 and over; 12% were age 75 and older). There was no apparent difference in efficacy between older and younger patients treated with Integrilin. The incidence of bleeding complications was higher in the elderly in both placebo and Integrilin groups, and the incremental risk of Integrilin-associated bleeding was greater in the older patients. No dose adjustment was made for elderly patients, but patients over 75 years of age had to weigh at least 50 kg to be enrolled in the PURSUIT study; no such limitation was stipulated in the ESPRIT study [see Adverse Reactions (6.1)].

Renal Impairment

Approximately 50% of eptifibatide is cleared by the kidney in patients with normal renal function. Total drug clearance is decreased by approximately 50% and steady-state plasma Integrilin concentrations are doubled in patients with an estimated CrCl <50 mL/min (using the Cockcroft-Gault equation). Therefore, the infusion dose should be reduced to 1 mcg/kg/min in such patients [see Dosage and Administration (2)]. The safety and efficacy of Integrilin in patients dependent on dialysis has not been established.

There has been only limited experience with overdosage of Integrilin. There were 8 patients in the IMPACT II study, 9 patients in the PURSUIT study, and no patients in the ESPRIT study who received bolus doses and/or infusion doses more than double those called for in the protocols. None of these patients experienced an intracranial bleed or other major bleeding.

Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis). Symptoms of acute toxicity were loss of righting reflex, dyspnea, ptosis, and decreased muscle tone in rabbits and petechial hemorrhages in the femoral and abdominal areas of monkeys.

From in vitro studies, eptifibatide is not extensively bound to plasma proteins and thus may be cleared from plasma by dialysis.

Mechanism of Action

Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa. When administered intravenously, eptifibatide inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. Platelet aggregation inhibition is reversible following cessation of the eptifibatide infusion; this is thought to result from dissociation of eptifibatide from the platelet.

Pharmacodynamics

Infusion of eptifibatide into baboons caused a dose-dependent inhibition of ex vivo platelet aggregation, with complete inhibition of aggregation achieved at infusion rates greater than 5 mcg/kg/min. In a baboon model that is refractory to aspirin and heparin, doses of eptifibatide that inhibit aggregation prevented acute thrombosis with only a modest prolongation (2- to 3-fold) of the bleeding time. Platelet aggregation in dogs was also inhibited by infusions of eptifibatide, with complete inhibition at 2 mcg/kg/min. This infusion dose completely inhibited canine coronary thrombosis induced by coronary artery injury (Folts model).

Human pharmacodynamic data were obtained in healthy subjects and in patients presenting with UA or NSTEMI and/or undergoing percutaneous coronary intervention. Studies in healthy subjects enrolled only males; patient studies enrolled approximately one-third women. In these studies, Integrilin inhibited ex vivo platelet aggregation induced by adenosine diphosphate (ADP) and other agonists in a dose- and concentration-dependent manner. The effect of Integrilin was observed immediately after administration of a 180-mcg/kg intravenous bolus. Table 4 shows the effects of dosing regimens of Integrilin used in the IMPACT II and PURSUIT studies on ex vivo platelet aggregation induced by 20 µM ADP in PPACK-anticoagulated platelet-rich plasma and on bleeding time. The effects of the dosing regimen used in ESPRIT on platelet aggregation have not been studied.

The Integrilin dosing regimen used in the ESPRIT study included two 180-mcg/kg bolus doses given 10 minutes apart combined with a continuous 2-mcg/kg/min infusion.

When administered alone, Integrilin has no measurable effect on PT or aPTT.

There were no important differences between men and women or between age groups in the pharmacodynamic properties of eptifibatide. Differences among ethnic groups have not been assessed.

Pharmacokinetics

The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses ranging from 90 to 250 mcg/kg and infusion rates from 0.5 to 3 mcg/kg/min. Plasma elimination half-life is approximately 2.5 hours. Administration of a single 180-mcg/kg bolus combined with an infusion produces an early peak level, followed by a small decline prior to attaining steady state (within 4-6 hours). This decline can be prevented by administering a second 180-mcg/kg bolus 10 minutes after the first. The extent of eptifibatide binding to human plasma protein is about 25%. Clearance in patients with coronary artery disease is about 55 mL/kg/h. In healthy subjects, renal clearance accounts for approximately 50% of total body clearance, with the majority of the drug excreted in the urine as eptifibatide, deaminated eptifibatide, and other, more polar metabolites. No major metabolites have been detected in human plasma.

Special Populations

Geriatric

Patients in clinical studies were older (range: 20-94 years) than those in the clinical pharmacology studies. Elderly patients with coronary artery disease demonstrated higher plasma levels and lower total body clearance of eptifibatide when given the same dose as younger patients. Limited data are available on lighter weight (<50 kg) patients over 75 years of age.

Renal Impairment

In patients with moderate to severe renal insufficiency (CrCl <50 mL/min using the Cockcroft-Gault equation), the clearance of eptifibatide is reduced by approximately 50% and steady-state plasma levels approximately doubled [see Use in Specific Populations (8.6) and Dosage and Administration (2)].

Hepatic Impairment

No studies have been conducted in patients with hepatic impairment.

Gender

Males and females have not demonstrated any clinically significant differences in the pharmacokinetics of eptifibatide.

Applies to eptifibatide: intravenous solution

Along with its needed effects, eptifibatide (the active ingredient contained in Integrilin) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking eptifibatide:

• Abdominal or stomach pain or swelling
• back pain or backaches
• bleeding from the bladder
• bleeding gums
• blood in the urine
• bloody or black, tarry stools
• blurred vision
• confusion
• constipation
• coughing up blood
• difficulty with breathing or swallowing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• headache
• headache, sudden and severe
• increased menstrual flow or vaginal bleeding
• nausea and vomiting
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• severe stomach pain
• shortness of breath
• sweating
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• weakness

• Pinpoint red spots on the skin

• Cough
• difficulty with swallowing
• fast heartbeat
• hives
• itching
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• skin rash
• tightness in the chest
• wheezing

• Difficulty with speaking
• double vision
• inability to move the arms, legs, or facial muscles
• inability to speak
• slow speech

Applies to eptifibatide: intravenous solution

General

Prior to approval by the FDA, the efficacy and safety of eptifibatide (the active ingredient contained in Integrilin) was evaluated in 8,737 patients. The average age of these patients was 62 years (range 20 to 94). Eighty nine percent were Caucasian, 5% were Black, and 5% were Hispanic. Sixty seven percent were male. The most common side effect was bleeding. Discontinuation of eptifibatide due to adverse events other than bleeding has been uncommon; no single event occurred in greater than 0.5% of the study population.[Ref]

Hematologic

The overall incidence of intracranial hemorrhage or stroke in large clinical trials has ranged from 0.5% to 0.7% of patients, depending on dose. The incidences of thrombocytopenia and the need for platelet transfusions were similar between patients who received eptifibatide (the active ingredient contained in Integrilin) and those who received placebo, suggesting a stronger relationship between these problems and the use of heparin than with the use of the study drug. However, bleeding times and activated clotting times have been significantly higher among treated patients compared with placebo, in some cases despite receiving less heparin.

The incidence of thrombocytopenia (less than 100,000 cells/mcL) associated with eptifibatide is 1.2% to 6.8%, while severe thrombocytopenia (less than 50,000 cells/mcL) has been reported in 0.2% of patients. Platelet transfusions have been reported in 1.3% to 1.5% of patients.

The results of one study (PROTECT-TIMI-30 trial) indicate that in high-risk non ST segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) and treated with eptifibatide, increased age significantly correlated with bleeding events. Patients with reduced CrCl (less than or equal to 50 mL/min), given a full-dose eptifibatide infusion, were associated with a greater incidence of bleeding events. No bleeding events occurred in patients with reduced CrCl who received a reduced dose infusion. In addition, the majority of bleeding events occurred more than 6 hours after initiation of the eptifibatide infusion.

Risk factors for bleeding events in patients treated with glycoprotein (GP) IIb/IIIa inhibitors undergoing percutaneous coronary intervention have been identified and include advanced age, renal dysfunction, female gender, peripheral vascular disease, lower body weight, duration of GP IIb/IIIa inhibitor infusion, baseline platelet count, lower baseline hemoglobin, diabetes, and elevated peak activated clotting time. According to one study (CRUSADE trial) involving patients with non ST segment elevation acute coronary syndrome treated with a GPIIb/IIIa inhibitor, women are at a greater risk of bleeding than men, primarily because of excessive dosing.[Ref]

Hematologic side effects have been the most common and potentially serious. The incidences of major (intracranial hemorrhage or decreases in hemoglobin of 5 mg/dL or more) and minor bleeding (spontaneous gross hematuria or hematemesis, decreases in hemoglobin of less than 5 mg/dL) were 10.8% and 13.1% (PURSUIT study) and 4.7% and 14.2% (IMPACT II study), respectively. The incidences of the transfusion requirements in these two studies were 12.8% and 5.8%, respectively. The overall incidence of major bleeding was strongly associated with the incidence of coronary artery bypass graft surgery, and occurred mainly at arterial puncture sites. The next most common sites of bleeding--occurring in 0% to 6% of patients--were oropharyngeal (primarily gingival), gastrointestinal (incidences of upper and lower GI bleeding similar), genitourinary, then retroperitoneal. In the PURSUIT study, the risk of major bleeding was inversely related to body weight; patients less than 70 kg showed the highest correlation. Bleeding was cited as the reason to discontinue therapy in 3.5% to 8.0% of patients.

Fatal bleeding, thrombocytopenia, as well as cerebral, gastrointestinal and pulmonary hemorrhage (when used in combination with aspirin and heparin) have been reported during postmarketing experience.[Ref]

Hypersensitivity

Hypersensitivity reactions have been rare, and have included anaphylaxis in approximately 0.05% of patients.[Ref]

Cardiovascular

Cardiovascular side effects have included hypotension (7% versus 6% among placebo patients). Other cardiovascular side effects may have been related to underlying disease as they were typical of side effects among patients with unstable angina.[Ref]

Nervous system

Nervous system side effects have been limited to non hemorrhagic stroke in approximately 0.5% of treated and placebo patients in controlled trials.[Ref]

Musculoskeletal

Musculoskeletal discomfort--basically back pain--was reported in significantly more patients who received eptifibatide (the active ingredient contained in Integrilin) compared with placebo patients in the IMPACT II trial (50% versus 47%).[Ref]

Local

Local intravenous site reactions have been reported in significantly more treated patients compared with placebo patients in controlled trials. Arterial access sites are the most common sites of bleeding.[Ref]

Immunologic

Immunologic side effects have included postmarketing reports of IgG antibodies related to immune-mediated thrombocytopenia.[Ref]

Some side effects of Integrilin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.