Eptifibatide precautions

List of Precautions
Bleeding Precautions Care of the Femoral Artery Access Site in Patients Undergoing Percutaneous Coronary Intervention (PCI) Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents Minimization of Vascular and Other Trauma Laboratory Tests Maintaining Target aPTT and ACT Thrombocytopenia Drug Interactions Geriatric Use Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Pediatric Use Nursing Mothers -

Bleeding Precautions Care of the Femoral Artery Access Site in Patients Undergoing Percutaneous Coronary Intervention (PCI)
In patients undergoing PCI, treatment with eptifibatide is associated with an increase in major and minor bleeding at the site of arterial sheath placement. After PCI, eptifibatide 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 eptifibatide 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 eptifibatide should be discontinued and sheath hemostasis should be achieved at least 2 to 4 hours before hospital discharge.

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Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents
In the IMPACT II, PURSUIT and ESPRIT studies, eptifibatide was used concomitantly with unfractionated heparin and aspirin (see CLINICAL STUDIES). In the ESPRIT study, clopidogrel or ticlopidine were used routinely starting the day of PCI. Because eptifibatide inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect hemostasis, including thrombolytics, oral anticoagulants, nonsteroidal anti-inflammatory drugs, and dipyridamole. To avoid potentially additive pharmacologic effects, concomitant treatment with other inhibitors of platelet receptor GP IIb/IIIa should be avoided.

There is only a small experience with concomitant use of eptifibatide and thrombolytics. In a study of 180 patients with acute myocardial infarction (AMI), eptifibatide (in regimens up to a bolus of 180 µg/kg followed by a continuous infusion of 0.75 µg/kg/min for 24 hours) was administered concomitantly with the approved "accelerated" regimen of alteplase, a thrombolytic agent. The studied regimens of eptifibatide did not increase the incidence of major bleeding or transfusion compared to the incidence seen when alteplase was given alone.

In the IMPACT II study, 15 patients received a thrombolytic agent in conjunction with the 135/0.5 dosing regimen, 2 of whom experienced a major bleed. In the PURSUIT study, 40 patients who received eptifibatide at the 180/2.0 dosing regimen received a thrombolytic agent, 10 of whom experienced a major bleed.

In another AMI study involving 181 patients, eptifibatide (in regimens up to a bolus of 180 µg/kg followed by a continuous infusion of up to 2.0 µg/kg/min for up to 72 hours) was administered concomitantly with streptokinase (1.5 million units over 60 minutes), another thrombolytic agent. At the highest studied infusion rates (1.3 µg/kg/min and 2.0 µg/kg/min), eptifibatide was associated with an increase in the incidence of bleeding and transfusions compared to the incidence seen when streptokinase was given alone.

These limited data on the use of eptifibatide in patients receiving thrombolytic agents do not allow an estimate of the bleeding risk associated with concomitant use of thrombolytics. Systemic thrombolytic therapy should be used with caution in patients who have received eptifibatide.

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Minimization of Vascular and Other Trauma
Arterial and venous punctures, intramuscular injections, and the use of urinary catheters, nasotracheal intubation, and nasogastric tubes should be minimized. When obtaining intravenous access, non-compressible sites (eg, subclavian or jugular veins) should be avoided.

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Laboratory Tests
Before infusion of eptifibatide, the following laboratory tests should be performed to identify preexisting hemostatic abnormalities: hematocrit or hemoglobin, platelet count, serum creatinine, and PT/aPTT. In patients undergoing PCI, the activated clotting time (ACT) should also be measured.

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Maintaining Target aPTT and ACT
The aPTT should be maintained between 50 and 70 seconds unless PCI is to be performed. In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT. Table 7 displays the risk of major bleeding according to the maximum aPTT attained within 72 hours in the PURSUIT study.



The ESPRIT study stipulated a target ACT of 200 to 300 seconds during PCI. Patients receiving eptifibatide 180/2.0/180 (mean ACT 284 seconds) experienced an increased incidence of bleeding relative to placebo (mean ACT 276 seconds), primarily at the femoral artery access site. At these lower ACTs, bleeding was less than previously reported with eptifibatide in the PURSUIT and IMPACT II studies.

The aPTT or ACT should be checked prior to arterial sheath removal. The sheath should not be removed unless the aPTT is <45 seconds or the ACT is <150 seconds.

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Thrombocytopenia
If the patient experiences a confirmed platelet decrease to <100,000/mm3, Integrilin® and heparin should be discontinued and the condition appropriately monitored and treated.

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Drug Interactions
Enoxaparin dosed as a 1.0-mg/kg subcutaneous injection q12h for four doses did not alter the pharmacokinetics of eptifibatide or the level of platelet aggregation in healthy adults.

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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 eptifibatide. The 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. 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.

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Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies in animals have been performed to evaluate the carcinogenic potential of eptifibatide. Eptifibatide was not genotoxic in the Ames test, the mouse lymphoma cell (L 5178Y, TK+/-) forward mutation test, the human lymphocyte chromosome aberration test, or the mouse micronucleus test. Administered by continuous intravenous infusion at total daily doses up to 72 mg/kg/day (about 4 times the recommended maximum daily human dose on a body surface area basis), eptifibatide had no effect on fertility and reproductive performance of male and female rats.

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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 eptifibatide. Because animal reproduction studies are not always predictive of human response, eptifibatide should be used during pregnancy only if clearly needed.

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Pediatric Use
Safety and effectiveness of eptifibatide in pediatric patients have not been studied.

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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 eptifibatide is administered to a nursing mother.

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