エスモロール塩酸塩

When esmolol and a catecholamine-depleting drug (eg, reserpine) are administered concomitantly, the effects of the drugs may be additive.

Concomitant administration of esmolol and morphine in healthy adults resulted in about a 50% increase in steady-state blood esmolol concentrations, although the pharmacokinetics of morphine were not affected.

Esmolol may prolong the effects of succinylcholine, although the onset of neuromuscular blockade is not affected. Succinylcholine-induced neuromuscular blockade has been prolonged by about 60% during concomitant esmolol administration in some patients. ... In addition, the duration of neuromuscular blockade was not prolonged in other patients during concomitant therapy.

Blood esmolol concentration may be increased slightly during concomitant warfarin therapy ... .

For more Interactions (Complete) data for ESMOLOL HYDROCHLORIDE (11 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ In general, overdosage of esmolol may be expected to produce effects that are mainly extensions of pharmacologic effects, particularly those involving the cardiovascular system. Overdosage of esmolol has resulted in cardiac arrest. As with other beta-adrenergic blocking agents, hypotension, symptomatic bradycardia, advanced AV block, intraventricular conduction defects, acute cardiac failure, seizures, and , in susceptible individuals, bronchospasm, hypoglycemia, electromechanical dissociation, and loss of consciousness might occur with esmolol overdosage. Cases of massive accidental overdosage of esmolol have occured because of errors in dilution. While some cases of overdosage have been fatal, others cases have resulted in permanent disability. Fatal overdosage has been associated with administration of a wide range of esmolol hydrochloride doses (0.625-2.5 g (12.5-50 mg/kg)). However, some patients have recovered completely from esmolol hydrochloride dose of up to 1.75 g given over 1 minute and from doses of 7.5 g given over 60 minutes during cardiovascular surgery. Generally, survival has occurred in those patients whose circulation could be supported while the effects of esmolol resolved.

/CASE REPORTS/ An infant was born to a woman who received intravenous esmolol for intrapartum supraventricular tachyarrhythmia. Despite the very short acting and cardio-selective beta-1 adrenergic blockade induced by that agent, neonatal effects can occur up to 48 hours after delivery.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Esmolol hydrochloride

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ Following IV infusion of esmolol hydrochloride doses up to 2 mg/kg per minute for 1 hour in dogs, no adverse effects were observed. However, doses of 3 mg/kg per minute for 1 hour produced ataxia and salivation, and doses of 4 mg/kg per minute for 1 hour produced muscular rigidity, head tremors, seizures, ptosis, emesis, vocalization, hyperpnea, and prostration. All these adverse effects resolved within 90 minutes after completion of the infusion, and additional toxic manifestations were not apparent during 2 weeks of observation; however, autopsy revealed hemorrhagic foci on the lungs of one male dog.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Following continuous IV infusion of esmolol hydrochloride doses up to 400 ug/kg per minute for 2 weeks in dogs, no adverse effects were observed, but decreased muscle tone, salivation, constipation, and decreased food consumption occurred following continous IV infusion of 800 ug/kg per minute for 2 weeks. Following IV administration of esmolol hydrochloride dosages of 5 mg/kg daily for 2 weeks in rats, no adverse effects were observed, but reduced motor activity, ataxia, and respiratory distress occurred with dosages of 20 mg/kg daily for 2 weeks; death occurred in some animals at 40 mg/kg daily for 2 weeks.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats and rabbits using esmolol hydrochloride doses up to 3 mg/kg per minute ... and 1 mg/kg per minute, respectively, for 30 minutes daily, have not revealed evidence of maternotoxicity, embryotoxicity, or teratogenicity. However, esmolol hydrochloride doses of 10 mg/kg per minute produced maternal toxicity and death in rats, and doses of 2.5 mg/kg per minute produced minimal maternal toxicity and increased fetal resorptions in rabbits.

/GENOTOXICITY/ Esmolol did not exhibit mutagenic activity in vitro several mammallian cell (eg, Chinese hamster ovary) and microbial (Ames test) systems.

/GENOTOXICITY/ Esmolol did not exhibit mutagenic activity in vitro in ... human lymphocytes.

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, hyperkalemia, and hypoglycemia if they occur. 3. Treat bradycardia with atropine, ... IV; isoproterenol ... ; or cardiac pacing. 4. Treat bronchospasm with nebulized bronchodilators. 5. Continuously monitor the vital signs and ECG for at least 6 hours after ingestion. /Esmolol, Beta-adrenergic blockers/

Specific drugs and antidotes. 1. Bradycardia and hypotension resistant to... /normal/ measures should be treated with glucagon, ... . Epinephrine (intravenous) infusion ... and titrating to effect. 2. Wide complex conduction deffects caused by membrane-depressant poisoning may respond to sodium bicarbonate, ... , as given for tricyclic antidepressant overdose. 3. Torsades de pointes polymorphous ventricular tachycardia associated with QT prolongation resulting from sotalol poisoning can be treated with isoproterenol infusion, magnesium, or overdrive pacing. Correction of hypokalemia may also be useful. /Esmolol, Beta-adrenergic blockers/

Decontamination. 1. Prehospital. Administer activated charcoal if available. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions, especially involving propranolol. Gastric emptying is not necessary for small ingestions if activated charcoal can be given promptly. /Esmolol, Beta-adrenergic blockers/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

LD50 Mice iv 93 mg/kg

LD50 Rat iv 71 mg/kg

LD50 Rabbit iv 40 mg/kg

LD50 Dogs iv 32 mg/kg

LD50 Mice iv 452 mg/kg /De-estrified metabolite (ASL 8123) of esmolol/

Esmolol, used as a cardiovascular drug, was approved by FDA for marketing in the United States on 12/31/86.

Esmolol, used as a beta adrenergic blocking agent, was approved by FDA for marketing in the United States 8/88.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl esmolol hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Parenteral concentrate, 250 mg/ml, for injection for IV infusion, Brevibloc (with alcohol 25% and propylene glycol 25%), Baxter; Injection, 10 mg/ml Brevibloc, Baxter

Brevibloc