Esmolol hydrochloride (Brevibloc Injection / Brevibloc Premixed Injection)

1. Health Canada Product Monograph — Esmolol hydrochloride

• Used in the perioperative setting to manage rapid heart rate and high blood pressure in patients at risk of reduced blood flow to the heart muscle.
• Used for rapid, short-term control of a fast ventricular rate in atrial fibrillation or atrial flutter when a short-acting agent is preferred.
• Intended for short-term use only, up to 24 hours, and is not used for chronic or long-term therapy.

• Has not been formally studied in pregnant women, and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
• If treatment is considered, uteroplacental blood flow should be monitored, since beta-blockers can reduce blood flow to the placenta.
• Use in the second or third trimester or during labour can cause a slow fetal heart rate that continues after the infusion is stopped, and the beta-blocking effect can persist in the newborn for several days after birth, potentially causing low heart rate, breathing difficulty, low blood sugar, or low blood pressure that may require intensive care.

• Not known whether esmolol passes into human breast milk, so caution should be used if this medication is given to a nursing mother.

• Safety and effectiveness in patients 65 years of age and older have not been formally established, though esmolol is commonly used in this population in acute-care settings under close monitoring.

• Safety and effectiveness in children under 18 years of age have not been established.

• Esmolol is for intravenous use only, given and titrated by a physician in a hospital or acute-care monitored setting, and is not intended for outpatient or take-home use.
• For managing tachycardia and hypertension around intubation, a bolus of 1.5 mg/kg (up to 100 mg) is given over 30 seconds, 1 to 2 minutes before the procedure.
• For ongoing perioperative tachycardia and hypertension, a bolus of 1.5 mg/kg (up to 100 mg) is followed by a continuous infusion starting at 0.15 mg/kg/min, adjusted as needed up to 0.3 mg/kg/min to reach the desired heart rate or blood pressure.
• For atrial fibrillation or atrial flutter, treatment is started with a one-minute loading infusion followed by a maintenance infusion, with the dose titrated upward in a stepwise fashion under continuous monitoring of heart rate and blood pressure until the desired response is reached.
• Because this is a continuously titrated intravenous infusion managed entirely by clinical staff, the concept of a missed dose does not apply.
• The drug itself does not require dose adjustment for kidney impairment, though it should be used with caution in patients with kidney disease since its inactive breakdown product is cleared more slowly.

• Low blood pressure, often without symptoms, is the most frequently reported effect.
• Reduced heart rate (bradycardia) may occur.
• Sweating (hyperhidrosis) may occur.
• Nausea may occur.
• Headache, dizziness, drowsiness, or confusion may occur.
• Reactions at the IV site, such as redness, swelling, or discomfort, may occur.
• Vomiting may occur.
• Fatigue or agitation may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Esmolol may cause severe low blood pressure that requires reducing or stopping the infusion.
• Severe slowing of the heart rate or heart block may occur, particularly in patients with underlying conduction problems.
• Worsening or new heart failure, including pulmonary edema (fluid in the lungs), may occur.
• Bronchospasm, including wheezing and difficulty breathing, may occur, especially in patients with underlying lung disease.
• Cardiac arrest and, rarely, death have been reported, generally in critically ill or hemodynamically unstable patients.
• Serious reactions at the infusion site, including tissue death (necrosis) and blistering, can occur, especially if the drug leaks outside the vein.
• Because staff continuously monitor heart rate and blood pressure during administration, serious reactions are typically identified and managed immediately by the care team.

• Use with caution in patients with a history of heart failure, since beta-blockade can further weaken the heart's pumping ability.
• Use with caution in patients with asthma or other bronchospastic lung disease, since even a cardioselective beta-blocker can trigger bronchospasm.
• Use with caution in patients with diabetes, since esmolol can mask the warning signs of low blood sugar such as a fast heart rate.
• Use with caution in patients with impaired kidney function, since the inactive breakdown product accumulates and its elimination half-life is markedly prolonged.
• Use with caution in patients with peripheral circulatory disorders such as Raynaud's disease.
• Use with caution in patients with myasthenia gravis, since beta-blockers can cause muscle weakness.
• Use with caution in hypovolemic patients, since esmolol can blunt the compensatory rise in heart rate and increase the risk of low blood pressure.

• Contraindicated in patients who require inotropic drugs or vasopressors to maintain blood pressure and cardiac output.
• Contraindicated within 24 hours of intravenous cardiodepressant calcium-channel blockers such as verapamil or diltiazem, since fatal cardiac arrests have occurred with this combination.
• Contraindicated in patients with low blood pressure (hypotension).
• Contraindicated in sinus bradycardia and sick sinus syndrome.
• Contraindicated in second- and third-degree AV block.
• Contraindicated in pulmonary hypertension and right-sided heart failure secondary to it.
• Contraindicated in decompensated heart failure.
• Contraindicated in cardiogenic shock.
• Contraindicated in untreated pheochromocytoma (an adrenal tumour), unless alpha-blocker pretreatment has been given.
• Contraindicated in patients with known hypersensitivity to esmolol or any component of the product.

• Combining esmolol with intravenous calcium-channel blockers such as verapamil is contraindicated because of the risk of fatal cardiac arrest.
• Digoxin blood levels may rise modestly when given with esmolol, so patients on both drugs should be monitored.
• Concomitant use with morphine raises esmolol blood levels, so titration should proceed cautiously in these patients.
• Catecholamine-depleting drugs, such as reserpine, may have an additive effect with esmolol, increasing the risk of low blood pressure or marked bradycardia.
• Succinylcholine's muscle-relaxant effect may be prolonged when given with esmolol.
• Inhalational anesthetics can add to esmolol's negative effect on heart contraction, so caution is needed during anesthesia.
• Esmolol should not be used to control fast heart rate in patients receiving vasoconstrictive drugs with positive inotropic effects, such as epinephrine, norepinephrine, or dopamine, due to the risk of reduced cardiac contractility.
• Beta-blockers such as esmolol can increase the blood-glucose-lowering effect of insulin or other antidiabetic drugs and can mask the tachycardia that normally signals low blood sugar.
• Combining esmolol with clonidine, guanfacine, or moxonidine can increase the risk of rebound high blood pressure if those drugs are stopped; if therapy must be discontinued, the beta-blocker should be stopped first and gradually.

• Esmolol is given only by intravenous infusion in a monitored setting, so food interactions have not been studied and do not apply to its administration.

• Given as a continuous intravenous infusion, with or without an initial bolus dose, dosed and adjusted around the clock by the care team based on heart rate and blood pressure response rather than on a fixed home schedule.

• Vials should be stored at 15 to 25 degrees C.
• Premixed bags should be stored at 15 to 25 degrees C, protected from freezing and excessive heat.
• Esmolol is not compatible with 5% sodium bicarbonate solution or with furosemide, which can cause precipitation.

• This is a fast-acting intravenous beta-blocker used in the hospital to control a rapid heart rate and blood pressure, typically around surgery or during an episode of atrial fibrillation or flutter.
• It is given and continuously adjusted by the healthcare team through an IV line, with heart rate and blood pressure monitored closely throughout, and is used for no more than 24 hours at a time.
• Common effects include low blood pressure, a slower heart rate, sweating, and mild discomfort at the IV site.
• The care team should be alerted immediately to symptoms such as severe dizziness, chest tightness, difficulty breathing, or pain, burning, or swelling at the IV site, since these may signal a serious reaction.
• Because esmolol wears off within minutes of stopping the infusion, side effects usually resolve quickly once the dose is reduced or discontinued.
• There are no take-home doses or food or storage instructions for patients, as this medication is administered and stored exclusively by hospital staff.