en 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.
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, noncompressible sites (e.g., subclavian or jugular veins) should be avoided.
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.
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.
Table 7 Major Bleeding by Maximal aPTT Within 72 Hours in the PURSUIT Study Placebo
n (%) Eptifibatide 180/1.3*
n (%) Eptifibatide 180/2.0
n (%)
*
Administered only until the first interim analysis.
Maximum aPTT (seconds)
<50 44/721 (6.1%) 21/244 (8.6%) 44/743 (5.9%)
50 to 70 (recommended) 92/908 (10.1%) 28/259 (10.8%) 99/883 (11.2%)
>70 281/2786 (10.1%) 99/891 (11.1%) 345/2811 (12.3%)
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.
Drug Interactions
Enoxaparin dosed as a 1.0-mg/kg subcutaneous injection q12h for 4 doses did not alter the pharmacokinetics of eptifibatide or the level of platelet aggregation in healthy adults.
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 (see also ADVERSE REACTIONS).
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies in animals have been performed to eva luate 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 lym |
