A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Integrilin Side Effects, and Drug Interactions - Eptifibatide
Integrilin Side Effects, and Drug Interactions - Eptifibatide
SIDE EFFECTS
A total of 14,718 patients were treated in the two Phase III clinical
trials (PURSUIT and IMPACT II). Of these, 8737 received eptifibatide:
1300 at 135/0.5 for up to 24 hours, 1286 at 135/0.75 for up to 24
hours, 1472 at 180/1.3 for up to 72 hours, and 4679 at 180/2.0 for
up to 72 hours. The other 5981 patients received placebo. These
14,718 patients had a mean
age of 62 years (range 20
to 94 years). Eighty-nine percent
of the patients were Caucasian, with the remainder being predominantly
Black (5%) and Hispanic (5%). Sixty-seven percent
were men.
Because of the different regimens used in PURSUIT and IMPACT II,
data from the two studies were not pooled.
Bleeding
The incidences of bleeding
events and transfusions in the PURSUIT and IMPACT II studies are
shown in Table 7. 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 7
Bleeding Events and Transfusions in the PURSUIT
and IMPACT II Studies
| |
PURSUIT
Placebo
n (%)
|
Eptifibatide
180/ 1.3*
n (%)
|
Eptifibatide
180/ 2.0
n (%)
|
|
Patients
|
4696
|
1472
|
4679
|
|
Major bleedinga
|
425 (9.3%)
|
152 (10.5%)
|
498 (10.8%)
|
|
Minor bleedinga
|
347 (7.6%)
|
152 (10.5%)
|
604 (13.1%)
|
|
Requiring
Transfusionsb
|
490 (10.4%)
|
188 (12.8%)
|
601 (12.8%)
|
| |
IMPACT II
Placebo
n (%)
|
Eptifibatide
135/ 0.5
n (%)
|
Eptifibatide
135/ 0.75
n (%)
|
|
Patients
|
1285
|
1300
|
1286
|
|
Major bleedinga
|
55 (4.5%)
|
55 (4.4%)
|
58 (4.7%)
|
|
Minor bleedinga
|
115 (9.3%)
|
146 (11.7%)
|
177 (14.2%)
|
|
Requiring
Transfusionsb
|
66 (5.1%)
|
71 (5.5%)
|
74 (5.8%)
|
- Note: denominator is based on patients for
whom data are available
- * Administered only until the first interim analysis
- a For major and minor
bleeding, patients
are counted only once according to the most severe classification.
- b Includes transfusions of whole blood,
packed red blood
cells, fresh frozen plasma,
cryoprecipitate, platelets, and autotransfusion
during the initial
hospitalization.
As shown in Tables 8 and 9, the overall incidence
of major bleeding in
these studies was strongly related to the incidence
of coronary artery
bypass graft
(CABG) surgery; the excess bleeding
seen with eptifibatide, however, was seen only among the patients
who did not undergo CABG.
In the PURSUIT study, the greatest increase in major bleeding
in eptifibatide-treated patients compared to placebo
was associated with bleeding
at the femoral artery
access site (2.8% versus
1.3%). Oropharyngeal (primarily gingival), genito-urinary, gastrointestinal,
and retroperitoneal
bleeding were also
seen more commonly in eptifibatide-treated patients compared to
placebo. Among patients experiencing a major bleed in the IMPACT
II study, an increase in bleeding
on eptifibatide versus placebo
was observed only for the femoral
artery access site
(3.2% versus 2.8%).
Tables 8 and 9 display the incidence
of TIMI major bleeding
according to the cardiac
procedures carried out in the PURSUIT and IMPACT II studies, respectively.
The most common bleeding
complications were related to cardiac
revascularization
(CABG-related or femoral
artery access site
bleeding).
Table 8
Major Bleeding by Procedures in the PURSUIT Study
|
|
Placebo
n (%)
|
Eptifibatide
180/ 1.3*
n (%)
|
Eptifibatide
180/ 2.0
n (%)
|
|
Patients
|
4577
|
1451
|
4604
|
|
Overall Incidence of Major Bleeding
|
425 (9.3%)
|
152 (10.5%)
|
498 (10.8%)
|
|
Breakdown by Procedure:
|
|
|
|
|
CABG
|
375 (8.2%)
|
123 (8.5%)
|
377 (8.2%)
|
|
Angioplasty without CABG
|
27 (0.6%)
|
16 (1.1%)
|
64 (1.4%)
|
|
Angiography without angioplasty
or CABG
|
11 (0.2%)
|
7 (0.5%)
|
29 (0.6%)
|
|
Medical Therapy Only
|
12 (0.3%)
|
6 (0.4%)
|
28 (0.6%)
|
- Denominators are based on the total number
of patients whose TIMI classification
was resolved.
- *Administered only until the first interim analysis
Table 9
Major Bleeding by Procedures in the IMPACT II Study
| |
Placebo
n (%)
|
Eptifibatide
135/ 0.5
n (%)
|
Eptifibatide
135/ 0.75
n (%)
|
|
Patients
|
1230
|
1249
|
1245
|
|
Overall Incidence of Major
Bleeding
|
55 (4.5%)
|
55 (4.4%)
|
58 (4.7%)
|
|
Breakdown of Bleeding by
|
|
Procedure:
|
|
CABG
|
35 (2.8%)
|
23 (1.8%)
|
26 (2.1%)
|
|
Angioplasty without CABG
|
20 (1.6%)
|
32 (2.6%)
|
32 (2.7%)
|
- Denominators are based on the total number
of patients whose TIMI classification
was resolved.
In the PURSUIT study, the risk
of major bleeding with
eptifibatide increased inversely with patient
weight. This relationship was most apparent
for patients weighing less than 70 kg. These trends were not apparent
in the IMPACT II study.
Bleeding adverse events resulting in discontinuation of study drug
were more frequent among patients receiving eptifibatide than placebo
(8% versus 1% in PURSUIT, 3.5% versus 1.9% in IMPACT II).
Intracranial Hemorrhage and Stroke
Intracranial hemorrhage
was rare in the PURSUIT clinical
study, with only 3 patients in the placebo
group, 1 patient in
the group treated with
eptifibatide 180/1.3 and 5 patients in the group
treated with eptifibatide 180/2.0 experiencing a hemorrhagic
stroke. The overall incidence
of stroke was 0.5% in
patients receiving eptifibatide 180/1.3, 0.7% in patients receiving
eptifibatide 180/2.0, and 0.8% in placebo
patients.
In the IMPACT II study, intracranial
hemorrhage was experienced
by 1 patient treated
with eptifibatide 135/0.5, 2 patients treated with eptifibatide
135/0.75 and 2 patients in the placebo
group. The overall incidence
of stroke was 0.5% in
patients receiving 135/0.5 eptifibatide, 0.7% in patients receiving
eptifibatide 135/0.75 and 0.7% in the placebo
group.
Thrombocytopenia
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 eptifibatide and placebo.
Allergic REACTIONS
In the IMPACT II study,
anaphylaxis was
reported in 1 patient
(0.08%) on placebo and
in no patients on eptifibatide.
In the PURSUIT study, anaphylaxis
was reported in 7 patients receiving placebo
(0.15%) and 7 patients receiving eptifibatide 180/2.0 (0.16%). In
the IMPACT II study, 2 patients (1 patient
(0.04%) receiving eptifibatide and 1 patient
(0.08%) receiving placebo) discontinued study drug
because of allergic
reactions. In the PURSUIT
study, anaphylaxis
was given as a reason for drug
discontinuation in 3 patients (0.05%) who received eptifibatide
and in none of the patients who received placebo.
Other Adverse REACTIONS
Serious non-bleeding events occurred in 19% of the eptifibatide
and 19% of the placebo
patients in the PURSUIT study. The only serious non-bleeding adverse
event that occurred at a rate
of at least 1% and was more common with eptifibatide than placebo
(7% versus 6%) was hypotension. Most of the serious non-bleeding
events consisted of cardiovascular
events typical of an
unstable angina population.
In the IMPACT II study, serious
non-bleeding events that occurred in greater than 1% of patients
were uncommon and similar in incidence
between placebo- and eptifibatide-treated patients.
Discontinuation of study drug
due to adverse events other than bleeding
was uncommon in both the PURSUIT and IMPACT II studies, with no
single event occurring in >0.5% of the study population. In
the PURSUIT study, non-bleeding adverse events leading to discontinuation
occurred in the eptifibatide and placebo
groups in the following body
systems with an incidence
of 0.1%: cardiovascular
system (0.3% and 0.3%),
digestive system
(0.1% and 0.1%), hemic/lymphatic system
(0.1% and 0.1%), nervous
system (0.3% and 0.4%),
urogenital system
(0.1% and 0.1%), and whole body
system (0.2% and 0.2%).
In the IMPACT II study, non-bleeding
adverse events leading to discontinuation occurred in the 135/0.5
eptifibatide and placebo
groups in the following body
systems with an incidence
of 0.1%: whole body (0.3%
and 0.1%), cardiovascular
system (1.4% and 1.4%),
digestive system
(0.2% and 0%), hemic/lymphatic system
(0.2% and 0%), nervous
system (0.3% and 0.2%),
and respiratory
system (0.1% and 0.1%).
DRUG INTERACTIONS
No information provided.
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