phocyte 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.
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.
Pediatric Use
Safety and effectiveness of eptifibatide in pediatric patients have not been studied.
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.
ADVERSE REACTIONS
A total of 16,782 patients were treated in the Phase III clinical trials (PURSUIT, ESPRIT, and IMPACT II). 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
The incidences of bleeding events and transfusions in the PURSUIT, IMPACT II, and ESPRIT studies are shown in Table 8. Bleeding was classified as major or minor by the criteria of the TIMI study group. Major bleeding events consisted of intracranial hemorrhage and other bleeding that led to decreases in hemoglobin greater than 5 g/dL. Minor bleeding events 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 8 Bleeding Events and Transfusions in the PURSUIT, ESPRIT, and IMPACT II Studies PURSUIT
Placebo
n (%) Eptifibatide 180/1.3*
n (%) Eptifibatide 180/2.0
n (%)
Note: Denominator is based on patients for whom data are available.
*
Administered only until the first interim analysis.
†
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.
Patients 4696 1472 4679
Major bleeding† 425 (9.3%) 152 (10.5%) 498 (10.8%)
Minor bleeding† 347 (7.6%) 152 (10.5%) 604 (13.1%)
Requiring transfusions‡ 490 (10.4%) 188 (12.8%) 601 (12.8%)
ESPRIT
Placebo
n (%) Eptifibatide 18 |
