ESMOLOL Drug Interactions: What You Need to Know

INTERACTIONS Concomitant use of esmolol hydrochloride in sodium chloride 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 esmolol hydrochloride in sodium chloride injection’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). Esmolol hydrochloride in sodium chloride injection 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 esmolol hydrochloride in sodium chloride injection leads to an approximate 10% to 20% increase of digoxin blood levels at some time points. Digoxin does not affect esmolol hydrochloride in sodium chloride injection pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use increases the risk of bradycardia.
• Anticholinesterases: Esmolol hydrochloride in sodium chloride injection 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 esmolol hydrochloride in sodium chloride injection 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 esmolol hydrochloride in sodium chloride injection.
• Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use esmolol hydrochloride in sodium chloride injection to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.
• Digitalis glycosides: Risk of bradycardia ( 7 )
• Anticholinesterases: Prolongs neuromuscular blockade ( 7 )
• Antihypertensive agents: Risk of rebound hypertension ( 7 )
• Sympathomimetic drugs: Dose adjustment needed ( 7 )
• Vasoconstrictive and positive inotropic effect substances: Avoid concomitant use ( 7 )

Esmolol hydrochloride in sodium chloride injection is contraindicated in patients with:

• Severe sinus bradycardia: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see Warnings and Precautions (5.2) ] .
• Heart block greater than first degree: Second- or third-degree atrioventricular block may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see Warnings and Precautions (5.2) ] .
• Sick sinus syndrome: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see Warnings and Precautions (5.2) ] .
• Decompensated heart failure: May worsen heart failure.
• Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest.
• IV administration of cardiodepressant calcium-channel antagonists (e.g., verapamil) and esmolol hydrochloride in sodium chloride injection in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving esmolol hydrochloride in sodium chloride injection and intravenous verapamil.
• Pulmonary hypertension: May precipitate cardiorespiratory compromise.
• Hypersensitivity reactions, including anaphylaxis, to esmolol or any of the inactive ingredients of the product (cross-sensitivity between beta blockers is possible).
• Severe sinus bradycardia ( 4 )
• Heart block greater than first degree ( 4 )
• Sick sinus syndrome ( 4 )
• Decompensated heart failure ( 4 )
• Cardiogenic shock ( 4 )
• Coadministration of IV cardiodepressant calcium-channel antagonists (e.g. verapamil) in close proximity to esmolol hydrochloride in sodium chloride injection ( 4 , 7 )
• Pulmonary hypertension ( 4 )
• Known hypersensitivity to esmolol ( 4 )

AND PRECAUTIONS

• Risk of hypotension, bradycardia, and cardiac failure: Reduce or discontinue use ( 5.1 , 5.2 , 5.3 , 5.10 )
• Risk of exacerbating reactive airway disease ( 5.5 )
• Diabetes mellitus: Increases the effect of hypoglycemic agents and masks hypoglycemic tachycardia ( 5.6 )
• Risk of unopposed alpha-agonism and severe hypertension in untreated pheochromocytoma ( 5.9 )
• Risk of myocardial ischemia when abruptly discontinued in patients with coronary artery disease ( 5.12 , 5.15 )

5.1 Hypotension Hypotension can occur at any dose but is dose-related. Patients with hemodynamic compromise or on interacting medications are at particular risk. Severe reactions may include loss of consciousness, cardiac arrest, and death. For control of ventricular heart rate, maintenance doses greater than 200 mcg per kg per min are not recommended. Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol hydrochloride. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.

5.2 Bradycardia Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of esmolol hydrochloride. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving esmolol hydrochloride <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . If severe bradycardia develops, reduce or stop esmolol hydrochloride.

5.3 Cardiac Failure Beta blockers, like esmolol hydrochloride, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. At the first sign or symptom of impending cardiac failure, stop esmolol hydrochloride and start supportive therapy <span class="opacity-50 text-xs">[see Overdosage (10) ]</span> .

5.4 Intraoperative and Postoperative Tachycardia and Hypertension Monitor vital signs closely and titrate esmolol hydrochloride slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.

5.5 Reactive Airways Disease Patients with reactive airways disease should, in general, not receive beta blockers. Because of its relative beta 1 selectivity and titratability, titrate esmolol hydrochloride to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta 2 stimulating agent may be administered with appropriate monitoring of ventricular rate.

5.6 Use in Patients with Diabetes Mellitus and Hypoglycemia In patients with hypoglycemia, or diabetic patients (especially those with labile diabetes) who are receiving insulin or other hypoglycemic agents, beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be masked. Concomitant use of beta blockers and antidiabetic agents can enhance the effect of antidiabetic agents (blood glucose–lowering) .

5.7 Infusion Site Reactions Infusion site reactions have occurred with the use of esmolol hydrochloride. They include irritation, inflammation, and severe reactions (thrombophlebitis, necrosis, and blistering), in particular when associated with extravasation <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Avoid infusions into small veins or through a butterfly catheter. If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation.

5.8 Use in Patients with Prinzmetal&apos;s Angina Beta blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction. Do not use nonselective beta blockers.

5.9 Use in Patients with Pheochromocytoma If esmolol hydrochloride is used in the setting of pheochromocytoma, give it in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta-mediated vasodilation in skeletal muscle.

5.10 Use in Hypovolemic Patients In hypovolemic patients, esmolol hydrochloride can attenuate reflex tachycardia and increase the risk of hypotension.

5.11 Use in Patients with Peripheral Circulatory Disorders In patients with peripheral circulatory disorders (including Raynaud’s disease or syndrome, and peripheral occlusive vascular disease), esmolol hydrochloride may aggravate peripheral circulatory disorders.

5.12 Abrupt Discontinuation of Esmolol Hydrochloride Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta-blocker therapy. Observe patients for signs of myocardial ischemia when discontinuing esmolol hydrochloride. Heart rate increases moderately above pre-treatment levels 30 minutes after esmolol hydrochloride discontinuation.

5.13 Hyperkalemia Beta blockers, including esmolol hydrochloride, have been associated with increases in serum potassium levels and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of beta blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with esmolol hydrochloride.

5.14 Use in Patients with Metabolic Acidosis Beta blockers, including esmolol hydrochloride, have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may be associated with reduced cardiac contractility.

5.15 Use in Patients with Hyperthyroidism Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta-blocking therapy.

5.16 Use in Patients at Risk of Severe Acute Hypersensitivity Reactions When using beta blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions <span class="opacity-50 text-xs">[see Drug Interactions (7) ]</span> .

5.1 Hypotension Hypotension can occur at any dose but is dose-related. Patients with hemodynamic compromise or on interacting medications are at particular risk. Severe reactions may include loss of consciousness, cardiac arrest, and death. For control of ventricular heart rate, maintenance doses greater than 200 mcg per kg per min are not recommended. Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol hydrochloride. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.

5.2 Bradycardia Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of esmolol hydrochloride. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving esmolol hydrochloride <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . If severe bradycardia develops, reduce or stop esmolol hydrochloride.

5.3 Cardiac Failure Beta blockers, like esmolol hydrochloride, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. At the first sign or symptom of impending cardiac failure, stop esmolol hydrochloride and start supportive therapy <span class="opacity-50 text-xs">[see Overdosage (10) ]</span> .

5.4 Intraoperative and Postoperative Tachycardia and Hypertension Monitor vital signs closely and titrate esmolol hydrochloride slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.

5.5 Reactive Airways Disease Patients with reactive airways disease should, in general, not receive beta blockers. Because of its relative beta 1 selectivity and titratability, titrate esmolol hydrochloride to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta 2 stimulating agent may be administered with appropriate monitoring of ventricular rate.

5.6 Use in Patients with Diabetes Mellitus and Hypoglycemia In patients with hypoglycemia, or diabetic patients (especially those with labile diabetes) who are receiving insulin or other hypoglycemic agents, beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be masked. Concomitant use of beta blockers and antidiabetic agents can enhance the effect of antidiabetic agents (blood glucose–lowering) .

5.7 Infusion Site Reactions Infusion site reactions have occurred with the use of esmolol hydrochloride. They include irritation, inflammation, and severe reactions (thrombophlebitis, necrosis, and blistering), in particular when associated with extravasation <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Avoid infusions into small veins or through a butterfly catheter. If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation.

5.8 Use in Patients with Prinzmetal&apos;s Angina Beta blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction. Do not use nonselective beta blockers.

5.9 Use in Patients with Pheochromocytoma If esmolol hydrochloride is used in the setting of pheochromocytoma, give it in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta-mediated vasodilation in skeletal muscle.

5.10 Use in Hypovolemic Patients In hypovolemic patients, esmolol hydrochloride can attenuate reflex tachycardia and increase the risk of hypotension.

5.11 Use in Patients with Peripheral Circulatory Disorders In patients with peripheral circulatory disorders (including Raynaud’s disease or syndrome, and peripheral occlusive vascular disease), esmolol hydrochloride may aggravate peripheral circulatory disorders.

5.12 Abrupt Discontinuation of Esmolol Hydrochloride Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta-blocker therapy. Observe patients for signs of myocardial ischemia when discontinuing esmolol hydrochloride. Heart rate increases moderately above pre-treatment levels 30 minutes after esmolol hydrochloride discontinuation.

5.13 Hyperkalemia Beta blockers, including esmolol hydrochloride, have been associated with increases in serum potassium levels and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of beta blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with esmolol hydrochloride.

5.14 Use in Patients with Metabolic Acidosis Beta blockers, including esmolol hydrochloride, have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may be associated with reduced cardiac contractility.

5.15 Use in Patients with Hyperthyroidism Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta-blocking therapy.

5.16 Use in Patients at Risk of Severe Acute Hypersensitivity Reactions When using beta blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions <span class="opacity-50 text-xs">[see Drug Interactions (7) ]</span> .