Brevibloc

Dosage Forms And Strengths

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

Table 2 : BREVIBLOC Injection Presentations

Product Name	BREVIBLOC PREMIXED Injection (Esmolol Hydrochloride)	BREVIBLOC DOUBLE STRENGTH PREMIXED Injection (Esmolol Hydrochloride)	BREVIBLOC Injection (Esmolol Hydrochloride)
Total Dose	2500 mg / 250 mL	2000 mg / 100 mL	100 mg / 10 mL
Esmolol Hydrochloride Concentration	10 mg/mL	20 mg/mL	10 mg/mL
Packaging	250 mL Bag	100 mL Bag	10 mL Vial

Storage And Handling

BREVIBLOC PREMIXED Injection

NDC 10019-055-61, 2500 mg / 250 mL (10 mg/mL) Ready-to-use INTRAVIA Bags

BREVIBLOC DOUBLE STRENGTH PREMIXED Injection

NDC 10019-075-87, 2000 mg / 100 mL (20 mg/mL) Ready-to-use INTRAVIA Bags

BREVIBLOC Injection

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

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 Once drug has been withdrawn from ready-to-use bag, the bag should be used within 24 hours, with any unused portion discarded.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:

• Use aseptic technique.
• Suspend premixed bag from eyelet support.
• Remove plastic protector from delivery port at bottom of bag.
• Attach administration set.
• Refer to complete directions accompanying set.

Manufactured for: Baxter Healthcare Corporation, Deerfield, IL 60015 USA. Revised: .

Esmolol is a beta-blocker that affects the heart and circulation (blood flow through arteries and veins).

Esmolol is used to help keep the heart beating normally in people with certain heart rhythm disorders of the atrium (the upper chambers of the heart that allow blood to flow into the heart). Esmolol is used in people with atrial fibrillation or atrial flutter.

Esmolol is also used during surgery to help regulate blood pressure and heart rate.

Esmolol may also be used for purposes not listed in this medication guide.

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

You should not be treated with esmolol if you are allergic to it, or if you have:

• a serious heart condition such as "sick sinus syndrome" or "AV block" (second or third degree);

• a history of slow heart beats that have caused you to faint;

• heart failure;

• pulmonary hypertension (increased pressure inside the blood vessels of the lungs and heart); or

• a condition for which you are being treated with IV heart or blood pressure medication (such as diltiazem, nicardipine, or verapamil).

If possible before you receive esmolol, tell your doctor if you have:

• a heart condition called Prinzmetal's angina;

• asthma, chronic obstructive pulmonary disease (COPD), or other breathing disorder;

• diabetes;

• pheochromocytoma (tumor of the adrenal gland);

• overactive thyroid;

• allergies;

• kidney disease;

• coronary artery disease (hardened arteries); or

• peripheral vascular disease such as Raynaud's syndrome.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether esmolol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

In an emergency situation it may not be possible to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• digoxin, digitalis;

• blood pressure medication;

• diet pills, stimulants, ADHD medication (Ritalin, Adderall, and others);

• insulin or oral diabetes medicine; or

• medicines to treat asthma, colds, or allergies.

This list is not complete. Other drugs may interact with esmolol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

This section provides information on the proper use of a number of products that contain esmolol. It may not be specific to Brevibloc. Please read with care.

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed into one of your veins .

Use Brevibloc as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Supraventricular Tachycardia or Noncompensatory Sinus 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 intended for short-term use.

Intraoperative and Postoperative Tachycardia and/or Hypertension

Brevibloc (Esmolol Hydrochloride) 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 to prevent such events is not recommended.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The following adverse reaction rates are based on use of Brevibloc (Esmolol Hydrochloride) in clinical trials involving 369 patients with supraventricular tachycardia and over 600 intraoperative and postoperative patients enrolled in clinical trials. Most adverse effects observed in controlled clinical trial settings have been mild and transient. The most important and common adverse effect has been hypotension [see Warnings and Precautions (5.1)]. Deaths have been reported in post-marketing experience occurring during complex clinical states where Brevibloc was presumably being used simply to control ventricular rate [see Warnings and Precautions (5.5)].

Table 3 Clinical Trial Adverse Reactions (Frequency ≥3%)

System Organ Class (SOC)	Preferred MedDRA Term	Frequency
VASCULAR DISORDERS	Hypotension*
	Asymptomatic hypotension	25%
	Symptomatic hypotension (hyperhidrosis, dizziness)	12%
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	Infusion site reactions (inflammation and induration)	8%
GASTROINTESTINAL DISORDERS	Nausea	7%
NERVOUS SYSTEM DISORDERS	Dizziness	3%
	Somnolence	3%
* Hypotension resolved during Brevibloc (Esmolol Hydrochloride) infusion in 63% of patients. In 80% of the remaining patients, hypotension resolved within 30 minutes following discontinuation of infusion.

Clinical Trial Adverse Reactions (Frequency <3%)

Psychiatric Disorders

Confusional state and agitation (~2%)
Anxiety, depression and abnormal thinking (<1%)

Nervous System Disorders

Headache (~ 2%)
Paresthesia, syncope, speech disorder, and lightheadedness (<1%)
Convulsions (<1%), with one death

Vascular Disorders

Peripheral ischemia (~1%)
Pallor and flushing (<1%)

Gastrointestinal Disorders

Vomiting (~1%)
Dyspepsia, constipation, dry mouth, and abdominal discomfort (<1%)

Renal and Urinary Disorders

Urinary retention (<1%)

Post-Marketing Experience

In addition to the adverse reactions reported in clinical trials, the following adverse reactions have been reported in the post-marketing experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or to establish a causal relationship to drug exposure.

Cardiac Disorders

Cardiac arrest, Coronary arteriospasm

Skin and Subcutaneous Tissue Disorders

Angioedema, Urticaria, Psoriasis

Concomitant use of Brevibloc injection with other drugs that can lower blood pressure, reduce myocardial contractility, or interfere with sinus node function or electrical impulse propagation in the myocardium can exaggerate Brevibloc’s effects on blood pressure, contractility, and impulse propagation. Severe interactions with such drugs can result in, for example, severe hypotension, cardiac failure, severe bradycardia, sinus pause, sinoatrial block, atrioventricular block, and/or cardiac arrest. In addition, with some drugs, beta blockade may precipitate increased withdrawal effects. (See clonidine, guanfacine, and moxonidine below.) Brevibloc should therefore be used only after careful individual assessment of the risks and expected benefits in patients receiving drugs that can cause these types of pharmacodynamic interactions, including but not limited to:

• Digitalis glycosides: Concomitant administration of digoxin and Brevibloc leads to an approximate 10% to 20% increase of digoxin blood levels at some time points. Digoxin does not affect Brevibloc pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use increases the risk of bradycardia. • Anticholinesterases: Brevibloc prolonged the duration of succinylcholine-induced neuromuscular blockade and moderately prolonged clinical duration and recovery index of mivacurium. • Antihypertensive agents clonidine, guanfacine, or moxonidine: Beta blockers also increase the risk of clonidine-, guanfacine-, or moxonidine-withdrawal rebound hypertension. If, during concomitant use of a beta blocker, antihypertensive therapy needs to be interrupted or discontinued, discontinue the beta blocker first, and the discontinuation should be gradual. • Calcium channel antagonists: In patients with depressed myocardial function, use of Brevibloc with cardiodepressant calcium channel antagonists (e.g., verapamil) can lead to fatal cardiac arrests. • Sympathomimetic drugs: Sympathomimetic drugs having beta-adrenergic agonist activity will counteract effects of Brevibloc. • Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use Brevibloc to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.

Esmolol is a beta 1-selective (cardioselective) adrenergic receptor blocking agent.

Esmolol is used for the rapid control of ventricular rate.

Esmolol may also be used for purposes other than those listed in this medication guide.

Applies to esmolol: intravenous solution

Cardiovascular

Very common (10% or more): Hypotension
Uncommon (0.1% to 1%): Bradycardia, atrioventricular block, pulmonary arterial pressure increased, cardiac failure, ventricular extrasystoles, nodal rhythm, angina pectoris, peripheral ischemia, pallor, flushing, chest pain, asystole
Rare (0.01% to 0.1%): Sinus pause
Very rare (less than 0.01%): Sinus arrest, asystole, thrombophlebitis
Frequency not reported: Accelerated idioventricular rhythm, coronary arteriospasm, cardiac arrest[Ref]

Dermatologic

Very common (10% or more): Diaphoresis
Uncommon (0.1% to 1%): Skin discoloration, erythema
Very rare (less than 0.01%): Skin necrosis (due to extravasation)
Frequency not reported: Psoriasis, angioedema, urticaria[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, vomiting
Uncommon (0.1% to 1%): Dysgeusia, dyspepsia, constipation, dry mouth, abdominal pain[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary retention[Ref]

Local

Common (1% to 10%): Injection site reaction, infusion site reaction, infusion site inflammation, infusion site induration
Uncommon (0.1% to 1%): Infusion site burning, infusion site ecchymosis
Frequency not reported: Infusion site phlebitis, infusion site vesicles, blistering[Ref]

Nervous system

Common (1% to 10%): Dizziness, somnolence, headache, paresthesia, weakness
Uncommon (0.1% to 1%): Syncope, convulsion, speech disorder, light headedness[Ref]

Metabolic

Frequency not reported: Hyperkalemia, metabolic acidosis[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Musculoskeletal pain[Ref]

Ocular

Uncommon (0.1% to 1%): Visual impairment[Ref]

Other

Common (1% to 10%): Asthenia, fatigue
Uncommon (0.1% to 1%): Chills, pyrexia, edema, pain[Ref]

Psychiatric

Common (1% to 10%): Depression, anxiety, disturbance in attention, confusion, agitation
Uncommon (less than 1%): Abnormal thinking[Ref]

Respiratory

Uncommon (less than 1%): Dyspnea, pulmonary edema, bronchospasm, wheezing, nasal congestion, rhonchi, rales[Ref]

Some side effects of Brevibloc may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.