Stability data:
|
| Drug |
Stability
Refrigerated |
Stability
Room Temp. |
Reconstituted
Vial/Powder |
Notes |
| Eptifibatide - Integrilin |
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).
* Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) |
Solution |
Do not use beyond the labeled expiration date.
Protect from light until administration.
Discard any unused portion left in the vial. |
INDICATIONS AND USAGE
INTEGRILIN® is indicated:
* For the treatment of patients with acute coronary syndrome (unstable angina/non-ST-segment elevation myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). In this setting, INTEGRILIN has been shown to decrease the rate of a combined endpoint of death or new myocardial infarction.
* For the treatment of patients undergoing PCI, including those undergoing intracoronary stenting. In this setting, INTEGRILIN has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction, or need for urgent intervention.
CONTRAINDICATIONS
Treatment with eptifibatide is contraindicated in patients with:
* A history of bleeding diathesis, or evidence of active abnormal bleeding within the previous 30 days.
* Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy.
* Major surgery within the preceding 6 weeks.
* History of stroke within 30 days or any history of hemorrhagic stroke.
* Current or planned administration of another parenteral GP IIb/IIIa inhibitor.
* Dependency on renal dialysis.
* Known hypersensitivity to any component of the product.
WARNINGS
Bleeding
Bleeding is the most common complication encountered during eptifibatide therapy. Administration of eptifibatide is associated with an increase in major and minor bleeding, as classified by the criteria of the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with eptifibatide has been at the arterial access site for cardiac catheterization or from the gastrointestinal or genitourinary tract.In patients undergoing percutaneous coronary interventions, patients receiving eptifibatide experience an increased incidence of major bleeding compared to those receiving placebo without a significant increase in transfusion requirement. Special care should be employed to minimize the risk of bleeding among these patients. If bleeding cannot be controlled with pressure, infusion of eptifibatide and concomitant heparin should be stopped immediately.
Renal Insufficiency
Approximately 50% of eptifibatide is cleared by the kidney in patients with normal renal function. Total drug clearance is decreased by approximately 50% and steady-state plasma eptifibatide concentrations are doubled in patients with an estimated creatinine clearance <50 mL/min (using the Cockcroft-Gault equation). Therefore, the infusion dose should be reduced to 1 µg/kg/min in such patients (see DOSAGE AND ADMINISTRATION). There has been no clinical experience in patients dependent on dialysis.
Platelet Count <100,000/mm3
Because it is an inhibitor of platelet aggregation, caution should be exercised when administering eptifibatide to patients with a platelet count <100,000/mm3; there has been no clinical experience with eptifibatide initiated in patients with a platelet count <100,000/mm3. |
DOSAGE AND ADMINISTRATION
The safety and efficacy of eptifibatide has been established in clinical studies that employed concomitant use of heparin and aspirin. Different dose regimens of eptifibatide were used in the major clinical studies.
Acute Coronary Syndrome
The recommended adult dosage of eptifibatide in patients with acute coronary syndrome and normal renal function is an intravenous bolus of 180 µg/kg as soon as possible following diagnosis, followed by a continuous infusion of 2.0 µg/kg/min until hospital discharge or initiation of CABG surgery, up to 72 hours. If a patient is to undergo a percutaneous coronary intervention (PCI) while receiving eptifibatide, the infusion should be continued up to hospital discharge, or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy.
Patients with Creatinine Clearance Less Than 50 mL/min
The recommended adult dosage of eptifibatide in patients with acute coronary syndrome with an estimated creatinine clearance (using the Cockcroft-Gault equation)1 <50 mL/min is an intravenous bolus of 180 µg/kg as soon as possible following diagnosis, immediately followed by a continuous infusion of 1.0 µg/kg/min.
Percutaneous Coronary Intervention (PCI)
The recommended adult dosage of eptifibatide in patients with normal renal function is an intravenous bolus of 180 µg/kg administered immediately before the initiation of PCI followed by a continuous infusion of 2.0 µg/kg/min and a second 180-µg/kg bolus 10 minutes after the first bolus. Infusion should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of infusion is recommended.
Patients with Creatinine Clearance Less Than 50 mL/min
The recommended adult dose of eptifibatide in patients with an estimated creatinine clearance (using the Cockcroft-Gault equation)1 <50 mL/min is an intravenous bolus of 180 µg/kg administered immediately before the initiation of the procedure, immediately followed by a continuous infusion of 1.0 µg/kg/min and a second 180-µg/kg bolus administered 10 minutes after the first.
In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.
| 1. Use the Cockcroft-Gault equation with actual body weight to calculate creatinine clearance:
Men: Creatinine clearance (mL/min) = Weight (kg) x (140 – age) /
[72 x serum creatinine (mg/dL)]
Women: 0.85 x the value calculated for men. |
Aspirin and Heparin Dosing Recommendations
In the clinical trials that showed eptifibatide to be effective, most patients received concomitant aspirin and heparin. The recommended aspirin and heparin doses to be used are as follows:
Acute Coronary Syndrome -----------------------
Aspirin
160 to 325 mg orally initially and daily thereafter
Heparin
Target aPTT 50 to 70 seconds during medical management
-If weight ≥70 kg, 5000 U bolus followed by infusion of 1000 U/hr.
-If weight <70 kg, 60 U/kg bolus followed by infusion of 12 U/kg/hr.
Target ACT 200 to 300 seconds during PCI
-If heparin is initiated prior to PCI, additional boluses during PCI to maintain an ACT target of 200 to 300 seconds.
-Heparin infusion after the PCI is discouraged.
PCI ---------------------------------------------------------
Aspirin
160 to 325 mg orally 1 to 24 hours prior to PCI and daily thereafter
Heparin
Target ACT 200 to 300 seconds
-60 U/kg bolus initially in patients not treated with heparin within 6 hours prior to PCI.
-Additional boluses during PCI to maintain ACT within target.
-Heparin infusion after the PCI is strongly discouraged.
Patients requiring thrombolytic therapy should have eptifibatide infusions stopped.
Instructions for Administration
1. Like other parenteral drug products, INTEGRILIN® solutions should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
2. INTEGRILIN® may be administered in the same intravenous line as alteplase, atropine, dobutamine, heparin, lidocaine, meperidine, metoprolol, midazolam, morphine, nitroglycerin, or verapamil. INTEGRILIN® should not be administered through the same intravenous line as furosemide.
3. INTEGRILIN® may be administered in the same IV line with 0.9% NaCl or 0.9% NaCl/5% dextrose. With either vehicle, the infusion may also contain up to 60 mEq/L of potassium chloride. No incompatibilities have been observed with intravenous administration sets. No compatibility studies have been performed with PVC bags.
4. The bolus dose(s) of INTEGRILIN® should be withdrawn from the 10-mL vial into a syringe. The bolus dose(s) should be administered by IV push.
5. Immediately following the bolus dose administration, a continuous infusion of INTEGRILIN® should be initiated. When using an intravenous infusion pump, INTEGRILIN® should be administered undiluted directly from the 100-mL vial. The 100-mL vial should be spiked with a vented infusion set. Care should be taken to center the spike within the circle on the stopper top.
INTEGRILIN® is to be administered by volume according to patient weight.Patients should receive INTEGRILIN® according to the following table:
INTEGRILIN® Dosing Charts by Weight
| Patient Weight |
180 µg/kg
Bolus Volume |
2.0 µg/kg/min
Infusion Volume |
1.0 µg/kg/min
Infusion Volume |
| (kg) |
(lb) |
(from 2 mg/mL vial) |
(from 2 mg/mL 100-mL vial) |
(from 0.75 mg/mL 100-mL vial) |
(from 2 mg/mL 100-mL vial) |
(from 0.75 mg/mL 100-mL vial) |
| 37–41 |
81–91 |
3.4 mL |
2.0 mL/h |
6.0 mL/h |
1.0 mL/h |
3.0 mL/h |
| 42–46 |
92–102 |
4.0 mL |
2.5 mL/h |
7.0 mL/h |
1.3 mL/h |
3.5 mL/h |
| 47–53 |
103–117 |
4.5 mL |
3.0 mL/h |
8.0 mL/h |
1.5 mL/h |
4.0 mL/h |
| 54–59 |
118–130 |
5.0 mL |
3.5 mL/h |
9.0 mL/h |
1.8 mL/h |
4.5 mL/h |
| 60–65 |
131–143 |
5.6 mL |
3.8 mL/h |
10.0 mL/h |
1.9 mL/h |
5.0 mL/h |
| 66–71 |
144–157 |
6.2 mL |
4.0 mL/h |
11.0 mL/h |
2.0 mL/h |
5.5 mL/h |
| 72–78 |
158–172 |
6.8 mL |
4.5 mL/h |
12.0 mL/h |
2.3 mL/h |
6.0 mL/h |
| 79–84 |
173–185 |
7.3 mL |
5.0 mL/h |
13.0 mL/h |
2.5 mL/h |
6.5 mL/h |
| 85–90 |
186–198 |
7.9 mL |
5.3 mL/h |
14.0 mL/h |
2.7 mL/h |
7.0 mL/h |
| 91–96 |
199–212 |
8.5 mL |
5.6 mL/h |
15.0 mL/h |
2.8 mL/h |
7.5 mL/h |
| 97–103 |
213–227 |
9.0 mL |
6.0 mL/h |
16.0 mL/h |
3.0 mL/h |
8.0 mL/h |
| 104–109 |
228–240 |
9.5 mL |
6.4 mL/h |
17.0 mL/h |
3.2 mL/h |
8.5 mL/h |
| 110–115 |
241–253 |
10.2 mL |
6.8 mL/h |
18.0 mL/h |
3.4 mL/h |
9.0 mL/h |
| 116–121 |
254–267 |
10.7 mL |
7.0 mL/h |
19.0 mL/h |
3.5 mL/h |
9.5 mL/h |
| >121 |
>267 |
11.3 mL |
7.5 mL/h |
20.0 mL/h |
3.7 mL/h |
10.0 mL/h |
HOW SUPPLIED
INTEGRILIN® (eptifibatide) Injection is supplied as a sterile solution in 10-mL vials containing 20 mg of eptifibatide (NDC 0085-1177-01) and 100-mL vials containing either 75 mg of eptifibatide (NDC 0085-1136-01) or 200 mg of eptifibatide (NDC 0085-1177-02).
Vials should be stored refrigerated at 2–8°C (36–46°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).
Do not use beyond the labeled expiration date. Protect from light until administration. Discard any unused portion left in the vial.
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].
Schering Corporation
Kenilworth, NJ 07033 USA
INTEGRILIN® is a registered trademark of Millennium Pharmaceuticals, Inc.
Manufactured for Schering Corporation, Kenilworth, NJ 07033 USA.
U.S. Patent Nos. 5,686,570; 5,747,447; 5,756,451; 5,807,825; and 5,968,902.
B-30359402 9/06
Source: [package insert] |
