PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

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LOT EXP

NDC 10019-670-10
BREVIBLOC PREMIXED
Injection
Esmolol Hydrochloride
in Sodium Chloride
2,500 mg/250 mL
(10 mg/mL)

250 mL

Iso-Osmotic
No Preservative Added
Single Intravenous Use Only
EACH mL CONTAINS 10 mg ESMOLOL
HYDROCHLORIDE USP 5.9 mg SODIUM
CHLORIDE USP IN WATER FOR INJECTION
USP BUFFERED WITH 2.8 mg SODIUM
ACETATE TRIHYDRATE USP AND 0.546 mg GLACIAL ACETIC ACID USP
pH ADJUSTED WITH SODIUM HYDROXIDE AND/OR HYDROCHLORIC ACID
pH 5.0 (4.5-5.5) STERILE NONPYROGENIC
USUAL DOSAGE SEE PACKAGE INSERT
CAUTIONS CHECK FOR LEAKS BY SQUEEZING CONTAINER FIRMLY
IF LEAKS ARE FOUND DISCARD AS STERILITY MAY BE IMPAIRED USE
ONLY IF SOLUTION IS CLEAR COLORLESS TO LIGHT YELLOW DISCARD
UNUSED PORTION
DO NOT INTRODUCE ADDITIVES
MUST NOT BE USED IN SERIES CONNECTIONS

STORE AT 25°C (77°F) EXCURSIONS PERMITTED TO 15°-30°C
(59°-86°F) [SEE USP CONTROLLED ROOM TEMPERATURE]
PROTECT FROM FREEZING AVOID EXCESSIVE HEAT Rx only

MANUFACTURED BY
BAXTER LOGO
PREMIER ProRx®
USA

INTRAVIA CONTAINER
460-327-02** 2J1419**
****FOR PRODUCT INQUIRY
1 800 ANA DRUG
(1-800-262-3784)

LOT EXP

NDC 10019-666-10
BREVIBLOC PREMIXED
Double Strength Injection
Esmolol Hydrochloride in Sodium Chloride
2,000 mg/100 mL (20 mg/mL)

100 mL Iso-Osmotic No Preservative Added
Single Intravenous Use Only
EACH mL CONTAINS 20 mg ESMOLOL HYDROCHLORIDE
USP 4.1 mg SODIUM CHLORIDE USP IN WATER
FOR INJECTION USP BUFFERED WITH 2.8 mg SODIUM
ACETATE TRIHYDRATE USP AND 0.546 mg GLACIAL
ACETIC ACID USP pH ADJUSTED WITH SODIUM
HYDROXIDE AND/OR HYDROCHLORIC ACID pH 5.0
(4.5-5.5) STERILE NONPYROGENIC
USUAL DOSAGE SEE PACKAGE INSERT
CAUTIONS CHECK FOR LEAKS BY SQUEEZING
CONTAINER FIRMLY IF LEAKS ARE FOUND DISCARD AS
STERILITY MAY BE IMPAIRED USE ONLY IF SOLUTION IS
CLEAR COLORLESS TO LIGHT YELLOW DISCARD
UNUSED PORTION
DO NOT INTRODUCE ADDITIVES
MUST NOT BE USED IN SERIES CONNECTIONS

STORE AT 25°C (77°F) EXCURSIONS PERMITTED TO
15°-30°C (59°-86°F) [SEE USP CONTROLLED ROOM TEMPERATURE] PROTECT FROM FREEZING
AVOID EXCESSIVE HEAT Rx only

MANUFACTURED BY
BAXTER LOGO
****USA

PREMIER ProRx®
460-324-01 2J1420

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INDICATIONS & USAGE SECTION

Highlight: BREVIBLOC injection is a beta adrenergic blocker indicated for the short-term treatment of:

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Control of ventricular rate in supraventricular tachycardia including atrial fibrillation and atrial flutter and control of heart rate in noncompensatory sinus tachycardia (1.1)

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Control of perioperative tachycardia and hypertension (1.2)

1 INDICATIONS AND USAGE

1.1 Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

BREVIBLOC (Esmolol Hydrochloride) injection is indicated for the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. BREVIBLOC injection is also indicated in noncompensatory sinus tachycardia where, in the physician’s judgment, the rapid heart rate requires specific intervention. BREVIBLOC injection is intended for short-term use.

1.2 Intraoperative and Postoperative Tachycardia and/or Hypertension

BREVIBLOC (Esmolol Hydrochloride) injection is indicated for the short-term treatment of tachycardia and hypertension that occur during induction and tracheal intubation, during surgery, on emergence from anesthesia and in the postoperative period, when in the physician’s judgment such specific intervention is considered indicated.

Use of BREVIBLOC injection to prevent such events is not recommended.

DOSAGE & ADMINISTRATION SECTION

Highlight: •

Administer intravenously (2.1, 2.2)

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Titrate using ventricular rate or blood pressure at ≥4-minute intervals. (2.1, 2.2)

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Supraventricular tachycardia (SVT) or noncompensatory sinus tachycardia (2.1)

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Optional loading dose: 500 mcg per kg infused over one minute

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Then 50 mcg per kg per minute for the next 4 minutes

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Adjust dose as needed to a maximum of 200 mcg per kg per minute.

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Additional loading doses may be administered

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Perioperative tachycardia and hypertension (2.2)

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Loading dose: 500 mcg per kg over 1 minute for gradual control (1 mg per kg over 30 seconds for immediate control)

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Then 50 mcg per kg per min for gradual control (150 mcg per kg per minute for immediate control) adjusted to a maximum of 200 (tachycardia) or 300 (hypertension) mcg per kg per min (2.2)

2 DOSAGE AND ADMINISTRATION

2.1 Dosing for the Treatment of Supraventricular Tachycardia or

Noncompensatory Sinus Tachycardia

BREVIBLOC injection is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.

Table 1 Step-Wise Dosing

In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

Maintenance infusions may be continued for up to 48 hours.

2.2 Intraoperative and Postoperative Tachycardia and Hypertension

In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

Immediate Control

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Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.

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Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.

Gradual Control

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Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.

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Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.

Maximum Recommended Doses

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For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.

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For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.

2.3 Transition from BREVIBLOC Injection Therapy to Alternative Drugs

After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.

When transitioning from BREVIBLOC injection to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of BREVIBLOC injection as follows:

Thirty minutes following the first dose of the alternative drug, reduce the BREVIBLOC infusion rate by one-half (50%).

After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the BREVIBLOC infusion.

2.4 Directions for Use

BREVIBLOC injection is available in a pre-mixed bag and ready-to-use vial. BREVIBLOC injection is not compatible with Sodium Bicarbonate (5%) solution (limited stability) or furosemide (precipitation).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Premixed Bag

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The medication port is to be used solely for withdrawing an initial bolus from the bag.

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Use aseptic technique when withdrawing the bolus dose.

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Do not add any additional medications to the bag.

Figure 1: Two-Port INTRAVIA Bag

Ready-to-Use Vial

The Ready-to-use Vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared [see How Supplied/Storage and Handling (16.2)].

Compatibility with Commonly Used Intravenous Fluids

BREVIBLOC injection was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg esmolol hydrochloride per mL. BREVIBLOC injection was found to be compatible with the following solutions and was stable for at least 24 hours at controlled room temperature or under refrigeration:

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Dextrose (5%) Injection, USP

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Dextrose (5%) in Lactated Ringer’s Injection

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Dextrose (5%) in Ringer’s Injection

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Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP

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Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP

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Lactated Ringer’s Injection, USP

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Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP

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Sodium Chloride (0.45%) Injection, USP

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Sodium Chloride (0.9%) Injection, USP

DOSAGE FORMS & STRENGTHS SECTION

Highlight: •

Injection: 100 mg/10 mL (10 mg/mL) in 10 mL vial (3)

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Injection: 2500 mg/250 mL (10 mg/mL) in 250 mL Premixed Injection bag (3)

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Injection: 2000 mg/100 mL (20 mg/mL) in 100 mL Double Strength Premixed Injection bag (3)

3 DOSAGE FORMS AND STRENGTHS

All BREVIBLOC injection dosage forms are iso-osmotic solutions of esmolol hydrochloride in sodium chloride.

Table 2 BREVIBLOC Injection Presentations

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

BREVIBLOC PREMIXED Injection

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NDC 10019-670-10, 2500 mg / 250 mL (10 mg/mL) Ready-to-use INTRAVIA Bags

BREVIBLOC PREMIXED Double Strength Injection

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NDC 10019-666-10, 2000 mg / 100 mL (20 mg/mL) Ready-to-use INTRAVIA Bags

BREVIBLOC Injection

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NDC 10019-115-01, 100 mg / 10 mL (10 mg/mL) Ready-to-use Vials, Package of 25

16.2 Storage

Store at 25˚C (77˚F). Excursions permitted to 15˚-30˚C (59˚-86˚F) [see USP Controlled Room Temperature]. Protect from freezing. Avoid excessive heat.

Each bag contains no preservative. Once drug has been withdrawn from ready-to- use bag, the bag should be used within 24 hours, with any unused portion discarded.

Visually inspect the container. If the administration port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired.

Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

Do not remove unit from overwrap until ready to use. Do not use if overwrap has been previously opened or damaged. The overwrap is a moisture barrier. The inner bag maintains sterility of the solution. Tear overwrap at notch and remove premixed bag. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

Check for minute leaks by squeezing the inner bag firmly. If leaks are found, discard solution, as sterility may be impaired. Do not use unless the solution is clear (colorless to light yellow) and the seal is intact.

Preparation for intravenous administration:

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Use aseptic technique.

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Suspend premixed bag from eyelet support.

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Remove plastic protector from delivery port at bottom of bag.

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Attach administration set.

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Refer to complete directions accompanying set.

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