Aggrastat (Tirofiban Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

AGGRASTAT, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy. In this setting, AGGRASTAT has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure (for discussion of trial results and for definition of acute coronary syndrome see CLINICAL PHARMACOLOGY, Clinical Trials).

AGGRASTAT has been studied in a setting, as described in Clinical Trials, that included aspirin and heparin.

DOSAGE AND ADMINISTRATION

AGGRASTAT Injection must first be diluted to the same strength as AGGRASTAT Injection Premixed, as noted under Directions for Use.

Use with Aspirin and Heparin

In the clinical studies, patients received aspirin, unless it was contraindicated, and heparin. AGGRASTAT and heparin can be administered through the same intravenous catheter.

Precautions

AGGRASTAT is intended for intravenous delivery using sterile equipment and technique. Do not add other drugs or remove solution directly from the bag with a syringe. Do not use plastic containers in series connections; such use can result in air embolism by drawing air from the first container if it is empty of solution. Any unused solution should be discarded.

Directions for Use

Prior to use, AGGRASTAT Injection (250 mcg/mL) must be diluted to the same strength as AGGRASTAT Injection Premixed (50 mcg/mL). This may be achieved, for example, using either of the following two methods:

1. If using a 500 mL bag of sterile 0.9% sodium chloride or 5% dextrose in water, withdraw and discard 100 mL from the bag and replace this volume with 100 mL of AGGRASTAT Injection from two 50 mL vials, OR
2. If using a 250 mL bag of sterile 0.9% sodium chloride or 5% dextrose in water, withdraw and discard 50 mL from the bag and replace this volume with 50 mL of AGGRASTAT Injection from one 50 mL vial.

Mix well prior to administration.

AGGRASTAT Injection Premixed is supplied as 100 mL or 250 mL of 0.9% sodium chloride containing 50 mcg/mL tirofiban. It is supplied in IntraVia ³ containers (PL 2408 plastic). To open the IntraVia^® container, first tear off its foil overpouch. The plastic may be somewhat opaque because of moisture absorption during sterilization; the opacity will diminish gradually. Check for leaks by squeezing the inner bag firmly; if any leaks are found, the sterility is suspect and the solution should be discarded. Do not use unless the solution is clear and the seal is intact. Suspend the container from its eyelet support, remove the plastic protector from the outlet port, and attach a conventional administration set.

AGGRASTAT may be administered in the same intravenous line as dopamine, lidocaine, potassium chloride, and PEPCID^* (famotidine) Injection. AGGRASTAT should not be administered in the same intravenous line as diazepam.

Recommended Dosage

In most patients, AGGRASTAT should be administered intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then continued at 0.1 mcg/kg/min.

Patients with severe renal insufficiency (creatinine clearance <30 mL/min) should receive half the usual rate of infusion (see PRECAUTIONS, Severe Renal Insufficiency and CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Renal Insufficiency).The table below is provided as a guide to dosage adjustment by weight.

AGGRASTAT Injection must first be diluted to the same strength as AGGRASTAT Injection Premixed, as noted under Directions for Use.

Patient Weight (kg)	Most Patients		Severe Renal Impairment
	30 Min Loading Infusion Rate (mL/hr)	Maintenance Infusion Rate (mL/hr)	30 Min Loading Infusion Rate (mL/hr)	Maintenance Infusion Rate (mL/hr)
30-37	16	4	8	2
38-45	20	5	10	3
46-54	24	6	12	3
55-62	28	7	14	4
63-70	32	8	16	4
71-79	36	9	18	5
80-87	40	10	20	5
88-95	44	11	22	6
96-104	48	12	24	6
105-112	52	13	26	7
113-120	56	14	28	7
121-128	60	15	30	8
129-137	64	16	32	8
138-145	68	17	34	9
146-153	72	18	36	9

No dosage adjustment is recommended for elderly or female patients (see PRECAUTIONS, Geriatric Use). In PRISM-PLUS, AGGRASTAT was administered in combination with heparin for 48 to 108 hours. The infusion should be continued through angiography and for 12 to 24 hours after angioplasty or atherectomy.

HOW SUPPLIED

FOR INTRAVENOUS USE ONLY

AGGRASTAT Injection 12.5 mg per 50 mL (250 mcg per mL) is a non-preserved, clear, colorless concentrated sterile solution for intravenous infusion after dilution and is supplied as follows:

NDC 25208-001-01 50 mL vials.

AGGRASTAT Injection Premixed 5 mg tirofiban per 100 mL (50 mcg per mL) and 12.5 mg tirofiban per 250 mL (50 mcg per mL) are clear, non-preserved, sterile solutions premixed in a vehicle made iso-osmotic with sodium chloride, and are supplied as follows:

NDC 25208-002-01, 100 mL single-dose IntraVia^® containers (PL 2408 Plastic).

NDC 25208-002-02, 250 mL single-dose IntraVia^® containers (PL 2408 Plastic).

Storage

AGGRASTAT Injection

Store at 25°C (77°F) with excursions permitted between 15-30°C (59-86°F) (see USP Controlled Room Temperature). Do not freeze. Protect from light during storage.

AGGRASTAT Injection Premixed

Store at 25°C (77°F) with excursions permitted between 15-30°C (59-86°F) (see USP Controlled Room Temperature). Do not freeze. Protect from light during storage.

US Patent Nos: 5,292,756, 5,439,454, 5,849,843, and 5,998,019

AGGRASTAT (Tirofiban Hydrochloride Premixed) is manufactured for:

MEDICURE INTERNATIONAL, INC.
by:
BAXTER HEALTHCARE CORPORATION
Deerfield, IL 60015, USA
Distributed by:
MEDICURE PHARMA, INC.
Somerset, NJ 08873 USA

AGGRASTAT (Tirofiban Hydrochloride Injection) is manufactured for:

MEDICURE INTERNATIONAL, INC.
by:
BEN VENUE LABORATORIES
Bedford, OH 44146 USA
Distributed by:
MEDICURE PHARMA, INC.
Somerset, NJ 08873 USA

Issued October 2007
Printed in USA
07-19-54-779

¹ Registered trademark of Medicure International Inc. © 1998 Copyright used under license. All rights reserved.

² Bovill, E.G.; et al.: Hemorrhagic Events during Therapy with Recombinant Tissue-Type Plasminogen Activator, Heparin, and Aspirin for Acute Myocardial Infarction, Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial, Annals of Internal Medicine, 115(4): 256-265, 1991.

³ Registered trademark of Baxter International, Inc.