Eptifibatide: Package Insert and Label Information (Page 4 of 4)

14.2 Percutaneous Coronary Intervention (PCI)

IMPACT II (Eptifibatide Injection to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II)

IMPACT II was a multicenter, double-blind, randomized, placebo-controlled study conducted in the United States in 4010 patients undergoing PCI. Major exclusion criteria included a history of bleeding diathesis, major surgery within 6 weeks of treatment, gastrointestinal bleeding within 30 days, any stroke or structural CNS abnormality, uncontrolled hypertension, PT >1.2 times control, hematocrit <30%, platelet count <100,000/mm3 , and pregnancy.

Patient age ranged from 24 to 89 (mean 60) years, and 75% were male. The patients were 92% Caucasian, 5% Black, and 3% Hispanic. Forty-one percent of the patients underwent PCI for ongoing ACS. Patients were randomly assigned to 1 of 3 treatment regimens, each incorporating a bolus dose initiated immediately prior to PCI followed by a continuous infusion lasting 20 to 24 hours:

1) 135 mcg/kg bolus followed by a continuous infusion of 0.5 mcg/kg/min of eptifibatide injection (135/0.5);

2) 135 mcg/kg bolus followed by a continuous infusion of 0.75 mcg/kg/min of eptifibatide injection (135/0.75); or

3) a matching placebo bolus followed by a matching placebo continuous infusion.

Each patient received aspirin and an intravenous heparin bolus of 100 units/kg, with additional bolus infusions of up to 2000 additional units of heparin every 15 minutes to maintain an ACT of 300 to 350 seconds.

The primary endpoint was the composite of death, MI, or urgent revascularization, analyzed at 30 days after randomization in all patients who received at least 1 dose of study drug.

As shown in Table 7, each eptifibatide injection regimen reduced the rate of death, MI, or urgent intervention, although at 30 days, this finding was statistically significant only in the lower-dose eptifibatide injection group. As in the PURSUIT study, the effects of eptifibatide injection were seen early and persisted throughout the 30-day period.

Table 7. Clinical Events in the IMPACT II Study
Placebo
n (%)
Eptifibatide Injection
(135 mcg/kg bolus then 0.5 mcg/kg/min infusion)
n (%)
Eptifibatide Injection
(135 mcg/kg bolus then 0.75 mcg/kg/min infusion)
n (%)
* Kaplan-Meier estimate of event rate.

Patients

1285

1300

1286

Abrupt Closure

65 (5.1%)

36 (2.8%)

43 (3.3%)

p-value versus placebo

0.003

0.03

Death, MI, or Urgent Intervention

24 hours

123(9.6%)

86 (6.6%)

89 (6.9%)

p-value versus placebo

0.006

0.014

48 hours

131 (10.2%)

99 (7.6%)

102 (7.9%)

p-value versus placebo

0.021

0.045

30 days (primary endpoint)

149 (11.6%)

118 (9.1%)

128 (10%)

p-value versus placebo

0.035

0.179

Death or MI

30 days

110 (8.6%)

89 (6.8%)

95 (7.4%)

p-value versus placebo

0.102

0.272

6 months

151 (11.9%)*

136 (10.6%)*

130 (10.3%)*

p-value versus placebo

0.297

0.182

ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Eptifibatide Injection Therapy)

The ESPRIT study was a multicenter, double-blind, randomized, placebo-controlled study conducted in the United States and Canada that enrolled 2064 patients undergoing elective or urgent PCI with intended intracoronary stent placement. Exclusion criteria included MI within the previous 24 hours, ongoing chest pain, administration of any oral antiplatelet or oral anticoagulant other than aspirin within 30 days of PCI (although loading doses of thienopyridine on the day of PCI were encouraged), planned PCI of a saphenous vein graft or subsequent “staged” PCI, prior stent placement in the target lesion, PCI within the previous 90 days, a history of bleeding diathesis, major surgery within 6 weeks of treatment, gastrointestinal bleeding within 30 days, any stroke or structural CNS abnormality, uncontrolled hypertension, PT >1.2 times control, hematocrit <30%, platelet count <100,000/mm3 , and pregnancy.

Patient age ranged from 24 to 93 (mean 62) years, and 73% of patients were male. The study enrolled 90% Caucasian, 5% African American, 2% Hispanic, and 1% Asian patients. Patients received a wide variety of stents. Patients were randomized either to placebo or eptifibatide injection administered as an intravenous bolus of 180 mcg/kg followed immediately by a continuous infusion of 2 mcg/kg/min, and a second bolus of 180 mcg/kg administered 10 minutes later (180/2/180). Eptifibatide infusion was continued for 18 to 24 hours after PCI or until hospital discharge, whichever came first. Each patient received at least 1 dose of aspirin (162-325 mg) and 60 units/kg of heparin as a bolus (not to exceed 6000 units) if not already receiving a heparin infusion. Additional boluses of heparin (10-40 units/kg) could be administered in order to reach a target ACT between 200 and 300 seconds.

The primary endpoint of the ESPRIT study was the composite of death, MI, urgent target vessel revascularization (UTVR), and “bailout” to open-label eptifibatide injection due to a thrombotic complication of PCI (TBO) (e.g., visible thrombus, “no reflow,” or abrupt closure) at 48 hours. MI, UTVR, and TBO were evaluated by a blinded Clinical Events Committee.

As shown in Table 8, the incidence of the primary endpoint and selected secondary endpoints was significantly reduced in patients who received eptifibatide injection. A treatment benefit in patients who received eptifibatide injection was seen by 48 hours and at the end of the 30-day observation period.

Table 8. Clinical Events in the ESPRIT Study
* Eptifibatide injection was administered as 180 mcg/kg boluses at times 0 and 10 minutes and an infusion at 2 mcg/kg/min.

Placebo

(n=1024)

Eptifibatide Injection*

(n=1040)

Relative Risk

(95% CI)

p-value

Death, MI, UTVR, or Thrombotic “Bailout”

48 hours (primary endpoint)

108 (10.5%)

69 (6.6%)

0.629 (0.471, 0.84)

0.0015

30 days

120 (11.7%)

78 (7.5%)

0.64 (0.488, 0.84)

0.0011

Death, MI, or UTVR

48 hours

95 (9.3%)

62 (6%)

0.643 (0.472, 0.875)

0.0045

30 days (key secondary endpoint)

107 (10.4%)

71 (6.8%)

0.653 (0.49, 0.871)

0.0034

Death or MI

48 hours (primary endpoint)

94 (9.2%)

57 (5.5%)

0.597 (0.435, 0.82)

0.0013

30 days

104 (10.2%)

66 (6.3%)

0.625 (0.465, 0.84)

0.0016

The need for thrombotic “bailout” was significantly reduced with eptifibatide injection at 48 hours (2.1% for placebo, 1% for eptifibatide injection; p=0.029). Consistent with previous studies of GP IIb/IIIa inhibitors, most of the benefit achieved acutely with eptifibatide injection was in the reduction of MI. Eptifibatide injection reduced the occurrence of MI at 48 hours from 9% for placebo to 5.4% (p=0.0015) and maintained that effect with significance at 30 days.

There was no treatment difference with respect to sex in ESPRIT. Eptifibatide injection reduced the incidence of the primary endpoint in both men (95% confidence limits for relative risk: 0.54, 1.07) and women (0.24, 0.72) at 48 hours.

Follow-up (12-month) mortality data were available for 2024 patients (1017 on eptifibatide injection) enrolled in the ESPRIT trial (98.1% of the initial enrollment). Twelve-month clinical event data were available for 1964 patients (988 on eptifibatide injection), representing 95.2% of the initial enrollment. As shown in Table 9, the treatment effect of eptifibatide injection seen at 48 hours and 30 days appeared preserved at 6 months and 1 year. Most of the benefit was in reduction of MI.

Table 9. Clinical Events at 6 Months and 1 Year in the ESPRIT Study
Percentages are Kaplan-Meier event rates.

Placebo (n=1024)

Eptifibatide Injection

(n=1040)

Hazard Ratio

(95% CI)

Death, MI, or Target Vessel Revascularization

6 months

187 (18.5%)

146 (14.3%)

0.744 (0.599, 0.924)

1 year

222 (22.1%)

178 (17.5%)

0.762 (0.626, 0.929)

Death, MI

6 months

117 (11.5%)

77 (7.4%)

0.631 (0.473, 0.841)

1 year

126 (12.4%)

83 (8%)

0.63 (0.478, 0.832)

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Eptifibatide injection is supplied as a sterile solution in 10 mL vials containing 20 mg of eptifibatide (NDC 70436-026-80) and 100 mL vials containing 75 mg of eptifibatide (NDC 70436-027-80).

16.2 Storage

Vials should be stored refrigerated at 2° to 8°C (36° to 46°F). Vials may be transferred to room temperature storage* for a period not to exceed 2 months. Upon transfer, vial cartons must be marked by the dispensing pharmacist with a “DISCARD BY” date (2 months from the transfer date or the labeled expiration date, whichever comes first).

Protect from light until administration.

*Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Instruct patients to inform the doctor or healthcare provider about any medical conditions, medications, and allergies.

Manufactured by:

Hainan Poly Pharm. Co., Ltd.
Guilinyang Economic Development Area, Haikou, Hainan Province, China 571127

Distributed by:

Slate Run Pharmaceuticals, LLC, Columbus, Ohio 43215

10000060/03

Revised: 04/2019

PRINCIPAL DISPLAY PANEL — 20 mg CARTON LABEL

NDC 70436-026-80

Eptifibatide Injection, 20 mg/10 mL (2 mg/mL)

20mg carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 75 mg CARTON LABEL

NDC 70436-027-80

Eptifibatide Injection, 75 mg/100 mL (0.75 mg/mL)

75mg carton
(click image for full-size original)
EPTIFIBATIDE
eptifibatide injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70436-026
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
EPTIFIBATIDE (EPTIFIBATIDE) EPTIFIBATIDE 2 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
CITRIC ACID MONOHYDRATE
SODIUM HYDROXIDE
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:70436-026-80 10 mL in 1 VIAL None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA209864 07/22/2019
EPTIFIBATIDE
eptifibatide injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70436-027
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
EPTIFIBATIDE (EPTIFIBATIDE) EPTIFIBATIDE 0.75 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
CITRIC ACID MONOHYDRATE
SODIUM HYDROXIDE
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:70436-027-80 100 mL in 1 VIAL None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA209864 07/22/2019
Labeler — Slate Run Pharmaceuticals, LLC (039452765)

Revised: 01/2021 Slate Run Pharmaceuticals, LLC

Page 4 of 4 1 2 3 4

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.