Drug Ingredient Information
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 (esmolol) is also indicated in noncompensatory sinus tachycardia where, in the physician's judgment, the rapid heart rate requires specific intervention. BREVIBLOC (esmolol) 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 (esmolol) to prevent such events is not recommended.
In clinical trials 20-50% of patients treated with BREVIBLOC (Esmolol Hydrochloride) have experienced hypotension, generally defined as systolic pressure less than 90 mmHg and/or diastolic pressure less than 50 mmHg. About 12% of the patients have been symptomatic (mainly diaphoresis or dizziness). Hypotension can occur at any dose but is dose-related so that doses beyond 200 mcg/kg/min (0.2 mg/kg/min) are not recommended. Patients should be closely monitored, especially if pretreatment blood pressure is low. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.
Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. Continued depression of the myocardium with beta blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, BREVIBLOC (Esmolol Hydrochloride) should be withdrawn. Although withdrawal may be sufficient because of the short elimination half-life of BREVIBLOC (esmolol) , specific treatment may also be considered (see OVERDOSE). The use of BREVIBLOC (esmolol) for control of ventricular response in patients with supraventricular arrhythmias should be undertaken with caution when the patient is compromised hemodynamically or is taking other drugs that decrease any or all of the following: peripheral resistance, myocardial filling, myocardial contractility, or electrical impulse propagation in the myocardium. Despite the rapid onset and offset of the effects of BREVIBLOC (esmolol) , several cases of death have been reported in complex clinical states where BREVIBLOC (esmolol) was presumably being used to control ventricular rate.
Intraoperative and Postoperative Tachycardia and/or Hypertension
BREVIBLOC (Esmolol Hydrochloride) should not be used as the treatment for hypertension in patients in whom the increased blood pressure is primarily due to the vasoconstriction associated with hypothermia.
PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA BLOCKERS. Because of its relative beta1 selectivity and titratability, BREVIBLOC (Esmolol Hydrochloride) may be used with caution in patients with bronchospastic diseases. However, since beta1 selectivity is not absolute, BREVIBLOC (esmolol) should be carefully titrated to obtain the lowest possible effective dose. In the event of bronchospasm, the infusion should be terminated immediately; a beta2 stimulating agent may be administered if conditions warrant but should be used with particular caution as patients already have rapid ventricular rates.
Diabetes Mellitus and Hypoglycemia
BREVIBLOC (Esmolol Hydrochloride) should be used with caution in diabetic patients requiring a beta blocking agent. Beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.
||Because the acid metabolite of BREVIBLOC (esmolol) is primarily excreted unchanged by the kidney, BREVIBLOC (Esmolol Hydrochloride) should be administered with caution to patients with impaired renal function. The elimination half-life of the acid metabolite was prolonged ten-fold and the plasma level was considerably elevated in patients with end-stage renal disease.
|Drug Special Care
||Because of its short term usage no carcinogenicity, mutagenicity or reproductive performance studies have been conducted with BREVIBLOC (Esmolol Hydrochloride).
|Drug Drug Interactions
||Catecholamine-depleting drugs, e.g., reserpine, may have an additive effect when given with beta blocking agents. Patients treated concurrently with BREVIBLOC (Esmolol Hydrochloride) and a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.
A study of interaction between BREVIBLOC (esmolol) and warfarin showed that concomitant administration of BREVIBLOC (esmolol) and warfarin does not alter warfarin plasma levels. BREVIBLOC (esmolol) concentrations were equivocally higher when given with warfarin, but this is not likely to be clinically important.
When digoxin and BREVIBLOC (esmolol) were concomitantly administered intravenously to normal volunteers, there was a 10-20% increase in digoxin blood levels at some time points. Digoxin did not affect BREVIBLOC (esmolol) pharmacokinetics. When intravenous morphine and BREVIBLOC (esmolol) were concomitantly administered in normal subjects, no effect on morphine blood levels was seen, but BREVIBLOC (esmolol) steady-state blood levels were increased by 46% in the presence of morphine. No other pharmacokinetic parameters were changed.
The effect of BREVIBLOC (esmolol) on the duration of succinylcholine-induced neuromuscular blockade was studied in patients undergoing surgery. The onset of neuromuscular blockade by succinylcholine was unaffected by BREVIBLOC (esmolol) , but the duration of neuromuscular blockade was prolonged from 5 minutes to 8 minutes.
Although the interactions observed in these studies do not appear to be of major clinical importance, BREVIBLOC (esmolol) should be titrated with caution in patients being treated concurrently with digoxin, morphine, succinylcholine or warfarin.
While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Caution should be exercised when considering the use of BREVIBLOC (esmolol) and verapamil in patients with depressed myocardial function. Fatal cardiac arrests have occurred in patients receiving both drugs. Additionally, BREVIBLOC (esmolol) should not be used to control supraventricular tachycardia in the presence of agents which are vasoconstrictive and inotropic such as dopamine, epinephrine, and norepinephrine because of the danger of blocking cardiac contractility when systemic vascular resistance is high.
|Drug Pregnancy Interaction
||Teratogenicity studies in rats at intravenous dosages of BREVIBLOC (Esmolol Hydrochloride) up to 3000 mcg/kg/min (3 mg/kg/min) (ten times the maximum human maintenance dosage) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while a dosage of 10,000 mcg/kg/min (10 mg/kg/min) produced maternal toxicity and lethality. In rabbits, intravenous dosages up to 1000 mcg/kg/min (1 mg/kg/min) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while 2500 mcg/kg/min (2.5 mg/kg/min) produced minimal maternal toxicity and increased fetal resorptions.
Although there are no adequate and well-controlled studies in pregnant women, use of esmolol in the last trimester of pregnancy or during labor or delivery has been reported to cause fetal bradycardia, which continued after termination of drug infusion. BREVIBLOC (esmolol) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
|Drug Breast feeding Interaction
||It is not known whether BREVIBLOC (Esmolol Hydrochloride) is excreted in human milk; however, caution should be exercised when BREVIBLOC (esmolol) is administered to a nursing woman.
|Drug Machinery Interaction
|Drug More Information
||The safety and effectiveness of BREVIBLOC (Esmolol Hydrochloride) in pediatric patients have not been established.
|How to take the
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. 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 (esmolol) 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 (esmolol) 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 (esmolol) 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 (esmolol) 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.The dosage of BREVIBLOC (Esmolol Hydrochloride) should be reduced as follows:
Thirty minutes following the first dose of the alternative agent, reduce the infusion rate of (esmolol) by one-half (50%).
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 (esmolol) .
The use of infusions of BREVIBLOC (esmolol) up to 24 hours has been well documented; in addition, limited data from 24-48 hrs (N=48) indicate that BREVIBLOC (esmolol) 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.
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.
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 (esmolol) 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
||Brevibloc Premixed Injection (esmolol) (10 mg/mL) 250 mL IntraVia Bag
Brevibloc (esmolol) DOUBLE STRENGTH Premixed Injection (20 mg/mL) 100 mL IntraVia Bag
BREVIBLOC PREMIXED INJECTION (esmolol) (10 mg/mL) and BREVIBLOC (esmolol) 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 (esmolol) . 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 (esmolol) , 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.
Figure 1. Two-Port IntraVia Bag
Two-Port IntraVia Bag - illustration
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.
Fill out the patient information label supplied and apply to the inner bag.
Do not introduce additives to BREVIBLOC PREMIXED INJECTION (esmolol) or BREVIBLOC (esmolol) DOUBLE STRENGTH PREMIXED INJECTION.
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.
Directions for Use of the Ready-to-use Vials
Brevibloc (esmolol) Injection (10 mg/mL) 10 mL Ready-to-use Vial
Brevibloc (esmolol) 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 (esmolol) 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.
Compatibility with Commonly Used Intravenous Fluids
BREVIBLOC (esmolol) was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg Esmolol Hydrochloride per mL. BREVIBLOC (esmolol) 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 (esmolol) is NOT compatible with Sodium Bicarbonate (5%) Injection, USP.
|Excess Drug Consumption
||Esmolol is typically administered by a healthcare provider in a clinical setting where an emergency situation or overdose can be handled properly.
|Forgot Drug Consumption
||Since the medication will be administered by a healthcare provider, missing a dose should not occur.
|Stop Drug Consumption
|Common Drug Side Effects
Symptomatic hypotension (diaphoresis, dizziness) occurred in 12% of patients, and therapy was discontinued in about 11%, about half of whom were symptomatic. Asymptomatic hypotension occurred in about 25% of patients. Hypotension resolved during BREVIBLOC (Esmolol Hydrochloride) infusion in 63% of these patients and within 30 minutes after discontinuation of infusion in 80% of the remaining patients. Diaphoresis accompanied hypotension in 10% of patients. Peripheral ischemia occurred in approximately 1% of patients. Pallor, flushing, bradycardia (heart rate less than 50 beats per minute), chest pain, syncope, pulmonary edema and heart block have each been reported in less than 1% of patients. In two patients without supraventricular tachycardia but with serious coronary artery disease (post inferior myocardial infarction or unstable angina), severe bradycardia/sinus pause/asystole has developed, reversible in both cases with discontinuation of treatment.
Central Nervous System
Dizziness has occurred in 3% of patients; somnolence in 3%; confusion, headache, and agitation in about 2%; and fatigue in about 1% of patients. Paresthesia, asthenia, depression, abnormal thinking, anxiety, anorexia, and lightheadedness were reported in less than 1% of patients. Seizures were also reported in less than 1% of patients, with one death.
Bronchospasm, wheezing, dyspnea, nasal congestion, rhonchi, and rales have each been reported in less than 1% of patients.
Nausea was reported in 7% of patients. Vomiting has occurred in about 1% of patients. Dyspepsia, constipation, dry mouth, and abdominal discomfort have each occurred in less than 1% of patients. Taste perversion has also been reported.
Skin (Infusion Site)
Infusion site reactions including inflammation and induration were reported in about 8% of patients. Edema, erythema, skin discoloration, burning at the infusion site, thrombophlebitis, and local skin necrosis from extravasation have each occurred in less than 1% of patients.
Each of the following has been reported in less than 1% of patients: Urinary retention, speech disorder, abnormal vision, midscapular pain, rigors, and fever.
|Rare Drug Side Effects
|Very Rare Drug Side Effects
|Drug Side Effects Symptoms
|How to Store the
|How to Store the Medicine
||Store at 25°C (77°F). Excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.] PROTECT FROM FREEZING.