Esmolol – Brevibloc ®

Esmolol - Brevibloc ®

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Fluid-restricted patients:
2000 mg – 100 mL in Ready-to-use 100 mL
IntraVia Bags
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Secondary option:
[2.5 grams] [250 ml] [Titrate]
[5 grams] [500 ml] [Titrate]

Stability / Miscellaneous

Exp: 24 hours at room temperature or refrigerated.
Calculation of drip rate (ml/hr): 2.5 grams/250 ml: wt (kg) x mcg/min x 0.006

Minimum Dilution: Note: The use of esmolol with propylene glycol has been associated with a higher incidence of venous irritation at concentrations greater than 10 mg/mL on continued infusion. Mixed from the ampul at concentrations of greater than 10 mg/mL BREVIBLOC has, however, been well tolerated when administered via a central vein. A premixed bag is available from the manufacturer: 2000 mg/100 ml (solution osmolarity adjusted to 312 mOsmol/L).

Onset of action: I.V.: 2 to10 minutes (quickest when loading doses are administered)
Duration: 10-30 minutes. Prolonged following higher cumulative doses or extended duration of use.
Half-life: Adults: 9 minutes

INDICATIONS AND USAGE
Supraventricular Tachycardia
BREVIBLOC (Esmolol Hydrochloride) 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 is also indicated in noncompensatory sinus tachycardia where, in the physician’s judgment, the rapid heart rate requires specific intervention. BREVIBLOC is not intended for use in chronic settings where transfer to another agent is anticipated.

Intraoperative and Postoperative Tachycardia and/or Hypertension
BREVIBLOC (Esmolol Hydrochloride) is indicated for the 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 to prevent such events is not recommended.

DOSAGE AND ADMINISTRATION
Dosing Information:
SUPRAVENTRICULAR TACHYCARDIA
Dosage needs to be titrated, using ventricular rate as the guide.

An initial loading dose of 0.5 milligrams/kg (500 micrograms/kg) infused over a minute duration followed by a maintenance infusion of 0.05 milligrams/kg/min (50 micrograms/kg/min) for the next 4 minutes is recommended. This should give a rough guide with respect to the responsiveness of ventricular rate.

After the 4 minutes of initial maintenance infusion (total treatment duration being 5 minutes), depending upon the desired ventricular response, the maintenance infusion may be continued at 0.05 mg/kg/min or increased step-wise (e.g. 0.1 mg/kg/min, 0.15 mg/kg/min to a maximum of 0.2 mg/kg/min) with each step being maintained for 4 or more minutes.

If more rapid slowing of ventricular response is imperative, the 0.5 mg/kg loading dose infused over a 1 minute period may be repeated, followed by a maintenance infusion of 0.1 mg/kg/min for 4 minutes. Then, depending upon ventricular rate, another (and final) loading dose of 0.5 mg/kg/min infused over a 1 minute period may be administered followed by a maintenance infusion of 0.15 mg/kg/min. If needed, after 4 minutes of the 0.15 mg/kg/min maintenance infusion, the maintenance infusion may be increased to a maximum of 0.2 mg/kg/min.

In the absence of loading doses, constant infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes. Maintenance infusions (with or without loading doses) may be continued for as long as 24 hours.

The following table summarizes the above and assumes that 3 loading doses (the maximum recommended) are infused over 1 minute and incremental maintenance doses are required after each loading dose. There should be no 4th loading dose, but the maintenance dose may be incremented one more time.

In the treatment of supraventricular tachycardia, responses to BREVIBLOC (Esmolol Hydrochloride) usually (over 95%) occur within the range of 50 to 200 micrograms/kg/min (0.05 to 0.2 milligrams/kg/min). The average effective dosage is approximately 100 micrograms/kg/min (0.1 milligrams/kg/min) although dosages as low as 25 micrograms/kg/min (0.025 milligrams/kg/min) have been adequate in some patients. Dosages as high as 300 micrograms/kg/min (0.3 milligrams/kg/min) have been used, but these provide little added effect and increase the rate of adverse effects, so doses greater than 200 micrograms/kg/min are not recommended. Dosage of BREVIBLOC in supraventricular tachycardia must be individualized by titration in which each step consists of a loading dosage followed by a maintenance dosage.

This specific dosage regimen has not been studied intraoperatively and, because of the time required for titration, may not be optimal for intraoperative use.

The safety of dosages above 300 mcg/kg/min (0.3 mg/kg/min) has not been studied.

In the event of an adverse reaction, the dosage of BREVIBLOC may be reduced or discontinued. If a local infusion site reaction develops, an alternate infusion site should be used and caution should be taken to prevent extravasation. The use of butterfly needles should be avoided.

Abrupt cessation of BREVIBLOC in patients has not been reported to produce the withdrawal effects which may occur with abrupt withdrawal of beta blockers following chronic use in coronary artery disease (CAD) patients. However, caution should still be used in abruptly discontinuing infusions of BREVIBLOC in CAD patients.

After achieving an adequate control of the heart rate and a stable clinical status in patients with supraventricular tachycardia, transition to alternative antiarrhythmic agents such as propranolol, digoxin, or verapamil, may be accomplished.

A recommended guideline for such a transition is given below but the physician should carefully consider the labeling instructions for the alternative agent selected.

The dosage of BREVIBLOC (Esmolol Hydrochloride) should be reduced as follows:

1. Thirty minutes following the first dose of the alternative agent, reduce the infusion rate of BREVIBLOC by one-half (50%).
2. Following the second dose of the alternative agent, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue BREVIBLOC.

The use of infusions of BREVIBLOC up to 24 hours has been well documented; in addition, limited data from 24-48 hrs (N=48) indicate that BREVIBLOC is well tolerated up to 48 hours.

INTRAOPERATIVE AND POSTOPERATIVE TACHYCARDIA AND/OR HYPERTENSION
In the intraoperative and postoperative settings it is not always advisable to slowly titrate the dose of BREVIBLOC (Esmolol Hydrochloride) to a therapeutic effect. Therefore, two dosing options are presented: immediate control dosing and a gradual control when the physician has time to titrate.

1.Immediate Control
For intraoperative treatment of tachycardia and/or hypertension give an 80 mg (approximately 1 mg/kg) bolus dose over 30 seconds followed by a 150 mcg/kg/min infusion, if necessary. Adjust the infusion rate as required up to 300 mcg/kg/min to maintain desired heart rate and/or blood pressure.

2.Gradual Control
For postoperative tachycardia and hypertension, the dosing schedule is the same as that used in supraventricular tachycardia. To initiate treatment, administer a loading dosage infusion of 500 mcg/kg/min of BREVIBLOC for one minute followed by a four-minute maintenance infusion of 50 mcg/kg/min. If an adequate therapeutic effect is not observed within five minutes, repeat the same loading dosage and follow with a maintenance infusion increased to 100 mcg/kg/min (see above Supraventricular Tachycardia).

Notes:
1. Higher dosages (250-300 mcg/kg/min) may be required for adequate control of blood pressure than those required for the treatment of atrial fibrillation, flutter and sinus tachycardia. One third of the postoperative hypertensive patients required these higher doses.
2. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Directions for Use of Brevibloc Premixed Injection (10 mg/mL) and Brevibloc DOUBLE STRENGTH Premixed Injection (20 mg/mL)

This dosage form is prediluted to 100 or 250 mL to provide a ready-to-use, iso-osmotic solution of either 20 or 10 mg/mL esmolol hydrochloride in sodium chloride. It is important not to introduce additives to BREVIBLOC PREMIXED INJECTION or BREVIBLOC DOUBLE STRENGTH PREMIXED INJECTION. See Directions for Use of the Premixed Bag for additional information.

Directions for Use of the Premixed Bag
Brevibloc Premixed Injection (10 mg/mL) 250 mL IntraVia Bag

Brevibloc DOUBLE STRENGTH Premixed Injection (20 mg/mL) 100 mL IntraVia Bag

BREVIBLOC PREMIXED INJECTION (10 mg/mL) and BREVIBLOC DOUBLE STRENGTH PREMIXED INJECTION (20 mg/mL) are provided in ready-to-use, non-latex, non-PVC bags with two PVC ports, a medication port and a delivery port. The medication port is to be used solely for withdrawing an initial bolus from the bag; the medication withdrawal port is not intended for repeat bolus administration. The sterility of the premixed bag cannot be assured after repeat withdrawals from the bag. The use of aseptic technique is required when withdrawing the bolus dose. Do not add any additional medications to BREVIBLOC PREMIXED INJECTION. Each bag is for single-patient use only and contains no preservative. It is advised that once drug has been withdrawn from BREVIBLOC PREMIXED INJECTION, the bag should be used within 24 hours, with any unused portion discarded.

The Brevibloc Premixed Injection contains Esmolol Hydrochloride at a concentration of 10 milligrams/mL. When using a 10 milligrams/mL concentration, a loading dose of 0.5 milligrams/kg infused over 1 minute period of time, for a 70 kg patient, is 3.5 mL. The loading dose can be removed from the medication port of the premixed bag.

The Brevibloc DOUBLE STRENGTH Premixed Injection contains Esmolol Hydrochloride at a concentration of 20 milligrams/mL. When using a 20 milligrams/mL concentration, a loading dose of 0.5 milligrams/kg infused over 1 minute period of time, for a 70 kg patient, is 1.75 mL. The loading dose can be removed from the medication port of the premixed bag.

CAUTION
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.

TO OPEN
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.

Fill out the patient information label supplied and apply to the inner bag.

Do not introduce additives to BREVIBLOC PREMIXED INJECTION or BREVIBLOC DOUBLE STRENGTH PREMIXED INJECTION.

PREPARATION FOR INTRAVENOUS ADMINISTRATION
(use aseptic technique)

1. Suspend premixed bag from eyelet support.
2. Remove plastic protector from delivery port at bottom of bag.
3. Attach administration set. Refer to complete directions accompanying set.

Directions for Use of the Ready-to-use Vials
Brevibloc Injection (10 mg/mL) 10 mL Ready-to-use Vial
Brevibloc DOUBLE STRENGTH Injection (20 mg/mL) 5 mL Ready-to-use Vial

This dosage form is prediluted to provide a ready-to-use, iso-osmotic solution of either 10 or 20 mg/mL esmolol hydrochloride in sodium chloride recommended for BREVIBLOC intravenous administration. It may be used to administer the appropriate BREVIBLOC (Esmolol Hydrochloride) loading dosage infusions by hand-held syringe while the maintenance infusion is being prepared.

The 10 mL Ready-to-use Vial contains Esmolol Hydrochloride at a concentration of 10 milligrams/mL. When using a 10 milligrams/mL concentration, a loading dose of 0.5 mg/kg infused over 1 minute period of time, for a 70 kg patient is 3.5 mL.

The 5 mL DOUBLE STRENGTH Ready-to-use Vial contains Esmolol Hydrochloride at a concentration of 20 milligrams/mL. When using a 20 milligrams/mL concentration, a loading dose of 0.5 mg/kg infused over 1 minute period of time, for a 70 kg patient is 1.75 mL.

Directions for Use of the Brevibloc Concentrate 10 mL Ampul (250 milligrams/mL)
THE 2500 mg AMPUL IS NOT FOR DIRECT INTRAVENOUS INJECTION. THIS DOSAGE FORM IS A CONCENTRATED, POTENT DRUG WHICH MUST BE DILUTED PRIOR TO ITS INFUSION. BREVIBLOC SHOULD NOT BE ADMIXED WITH SODIUM BICARBONATE. BREVIBLOC SHOULD NOT BE MIXED WITH OTHER DRUGS PRIOR TO DILUTION IN A SUITABLE INTRAVENOUS FLUID.(See Compatibility Section below.)

Dilution: Aseptically prepare a 10 mg/mL infusion by adding two 2500 mg ampuls to a 500 mL container or one 2500 mg ampul to a 250 mL container of a compatible intravenous solution listed below. (Remove overage prior to dilution as appropriate.) This yields a final concentration of 10 mg/mL. The diluted solution is stable for at least 24 hours at room temperature. Note: The use of esmolol with propylene glycol has been associated with a higher incidence of venous irritation at concentrations greater than 10 mg/mL on continued infusion. Mixed from the ampul at concentrations of greater than 10 mg/mL BREVIBLOC has, however, been well tolerated when administered via a central vein.

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

* Dextrose (5%) Injection, USP
* Dextrose (5%) in Lactated Ringer’s Injection
* Dextrose (5%) in Ringer’s Injection
* Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP
* Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP
* Lactated Ringer’s Injection, USP
* Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP
* Sodium Chloride (0.45%) Injection, USP
* Sodium Chloride (0.9%) Injection, USP

BREVIBLOC is NOT compatible with Sodium Bicarbonate (5%) Injection, USP.

HOW SUPPLIED
BREVIBLOC PREMIXED INJECTION
NDC 10019-055-61, 2500 mg – 250 mL in Ready-to-use 250 mL IntraVia Bags

BREVIBLOC DOUBLE STRENGTH PREMIXED INJECTION
NDC 10019-075-87, 2000 mg – 100 mL in Ready-to-use 100 mL IntraVia Bags

BREVIBLOC INJECTION
NDC 10019-115-01, 100 mg – 10 mL Ready-to-use Vials, Package of 25

BREVIBLOC DOUBLE STRENGTH INJECTION
NDC 10019-085-01, 100 mg – 5 mL Ready-to-use Vials, Package of 10

BREVIBLOC CONCENTRATE
NDC 10019-025-18, 2500 mg – 10 mL Ampuls for Dilution, Package of 10

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.

Manufactured for
Baxter Healthcare Corporation
Deerfield, IL 60015 USA
Baxter, Brevibloc, Brevibloc Premixed and IntraVia are trademarks of Baxter International Inc.

Brevibloc (esmolol hydrochloride) and its packaging are protected by one or more of the following: U.S. Pat. Nos. 5,017,609; 5,849,843; 5,998,019; 6,310,094; 6,528,540; Pat. Pending.

For Product Inquiry 1 800 ANA DRUG (1-800-262-3784)
Revised: August 2005

Source: [package insert]