Included as part of the PRECAUTIONS section.
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 BREVIBLOC injection.
Decrease of dose or termination of infusion reverses hypotension, usually
within 30 minutes.
Bradycardia, including sinus pause, heart block, severe
bradycardia, and cardiac arrest have occurred with the use of BREVIBLOC
injection. 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 BREVIBLOC [see CONTRAINDICATIONS].
If severe bradycardia develops, reduce or stop BREVIBLOC.
Beta blockers, like BREVIBLOC injection, 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
BREVIBLOC and start supportive therapy [see OVERDOSAGE].
Intraoperative And Postoperative Tachycardia And/Or Hypertension
Monitor vital signs closely and titrate BREVIBLOC slowly
in the treatment of patients whose blood pressure is primarily driven by
vasoconstriction associated with hypothermia.
Reactive Airways Disease
Patients with reactive airways disease should, in
general, not receive beta blockers. Because of its relative beta1 selectivity and
titratability, titrate BREVIBLOC to the lowest possible effective dose. In the
event of bronchospasm, stop the infusion immediately; a beta2 stimulating agent
may be administered with appropriate monitoring of ventricular rates.
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).
Infusion Site Reactions
Infusion site reactions have occurred with the use of
BREVIBLOC injection. They include irritation, inflammation, and severe reactions
(thrombophlebitis, necrosis, and blistering), in particular when associated
with extravasation [see ADVERSE REACTIONS]. 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.
Use In Patients With Prinzmetal'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.
Use In Patients With Pheochromocytoma
If BREVIBLOC 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.
Use In Hypovolemic Patients
In hypovolemic patients, BREVIBLOC injection can
attenuate reflex tachycardia and increase the risk of hypotension.
Use In Patients With Peripheral Circulatory Disorders
In patients with peripheral circulatory disorders
(including Raynaud's disease or syndrome, and peripheral occlusive vascular
disease), BREVIBLOC may aggravate peripheral circulatory disorders.
Abrupt Discontinuation Of BREVIBLOC Injection
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 BREVIBLOC.
Heart rate increases moderately above pretreatment levels
30 minutes after BREVIBLOC discontinuation.
Beta blockers, including BREVIBLOC, 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 BREVIBLOC.
Use In Patients With Metabolic Acidosis
Beta blockers, including BREVIBLOC, have been reported to
cause hyperkalemic renal tubular acidosis. Acidosis in general may be
associated with reduced cardiac contractility.
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.
Use In Patients At Risk Of Severe Acute Hypersensitivity
When using beta blockers, patients at risk of
anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic,
Patients using beta blockers may be unresponsive to the
usual doses of epinephrine used to treat anaphylactic or anaphylactoid
reactions [see DRUG INTERACTIONS].
Because of its short term usage no carcinogenicity,
mutagenicity, or reproductive performance studies have been conducted with
Use In Specific Populations
Pregnancy Category C. Esmolol hydrochloride has
been shown to produce increased fetal resorptions with minimal maternal toxicity
in rabbits when given in doses approximately 8 times the maximum human
maintenance dose (300 mcg/kg/min). There are no adequate and well-controlled studies
in pregnant women. BREVIBLOC injection should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Teratogenicity studies in rats at intravenous dosages of
esmolol hydrochloride up to 3000 mcg/kg/min (10 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
produced maternal toxicity and lethality. In rabbits, intravenous dosages up to
1000 mcg/kg/min for 30 minutes daily produced no evidence of maternal toxicity,
embryotoxicity or teratogenicity, while 2500 mcg/kg/min produced minimal
maternal toxicity and increased fetal resorptions.
Labor And Delivery
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 injection should be
used during pregnancy only if the potential benefit justifies the potential risk
to the fetus.
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk and because of the potential
for serious adverse reactions in nursing infants from BREVIBLOC, a decision
should be made whether to discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the mother.
The safety and effectiveness of BREVIBLOC in pediatric
patients have not been established.
Clinical studies of BREVIBLOC injection did not include
sufficient numbers of subjects aged 65 and over to determine whether they
responded differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should usually
start at the low end of the dosing range, reflecting greater frequency of
decreased renal or cardiac function and of concomitant disease or other drug
No special precautions are necessary in patients with
hepatic impairment because BREVIBLOC is metabolized by red-blood cell esterases
[see CLINICAL PHARMACOLOGY].
No dosage adjustment is required for esmolol in patients
with renal impairment receiving a maintenance infusion of esmolol 150 mcg/kg
for 4 hours. There is no information on the tolerability of maintenance
infusions of esmolol using rates in excess of 150 mcg/kg or maintained longer
than 4 hours [see CLINICAL PHARMACOLOGY].