Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Orpha-Devel Handels und Vertriebs GmbH, Wintergasse 85/1B, A-3002 Purkersdorf, Austria
Pharmacotherapeutic group: Beta-blocking agents, selective
ATC code: C07AB09
Esmolol hydrochloride is a beta-selective (cardioselective) receptor blocking agent.
At therapeutic doses esmolol hydrochloride has no significant intrinsic sympathicomimetic activity (ISA) or membrane stabilising activity.
Esmolol hydrochloride, the active ingredient of ESMOLOL HYDROCHLORIDE 2500 mg powder, is chemically related to the phenoxy propanolamine class of beta-blockers.
Based on the pharmacological properties esmolol hydrochloride has a rapid onset and a very short duration of action by which the dose can be quickly adjusted:
However, the therapeutic effect is achieved sooner than the stabile plasma concentration. The infusion rate can then be adjusted to obtain the desired pharmacological effect.
Esmolol hydrochloride has the known hemodynamic and electrophysiologic effect of beta-blockers:
An uncontrolled pharmacokinetic/efficacy study was undertaken in 26 paediatric patients aged 2-16 years with supraventricular tachycardia (SVT). A loading dose of 1000 micrograms/kg of esmolol hydrochloride was administered followed by a continuous infusion of 300 micrograms/kg/min. SVT was terminated in 65% of patients within 5 minutes of the commencement of esmolol hydrochloride.
In a randomised but uncontrolled dose comparison study, efficacy was assessed in 116 paediatric patients aged 1 week – to 7 years with hypertension following repair of coarctation of the aorta. Patients received an initial infusion of either 125 micrograms/kg, 250 micrograms/kg, or 500 micrograms/kg, followed by a continuous infusion of 125 micrograms/kg /min, 250 micrograms/kg /min, or 500 micrograms/kg/min respectively. There was no significant difference in hypotensive effect between the 3 dosage groups. 54% of patients overall required medication other than esmolol hydrochloride to achieve satisfactory blood pressure control. No difference was apparent in this regard between the different dose groups.
The kinetics of esmolol hydrochloride are linear in healthy adults, the plasma concentration is proportional to the dose. If a loading dose is not used then steady-state blood concentrations are reached within 30 minutes with doses of 50 to 300 micrograms/Kg per minute.
The distribution half-life of esmolol hydrochloride is very fast, about 2 minutes.
The volume of distribution is 3.4 l/kg.
Esmolol hydrochloride is metabolised by esterases into an acid metabolite (ASL-8123) and methanol. This occurs through hydrolysis of the ester group by esterases in the red blood cells.
The metabolism of esmolol hydrochloride is independent when the dose is between 50 and 300 micrograms/kg/minute.
Esmolol hydrochloride is 55% bound to human plasma protein compared with only 10% for the acid metabolite.
The elimination half-life after intravenous administration is approximately 9 minutes.
The total clearance is 285 ml/kg/minute; this is independent of the circulation of the liver or any other organ. Esmolol hydrochloride is excreted by the kidneys, partly unchanged (less than 2% of the administered amount), partly as acid metabolite that has a weak (less than 0.1% of esmolol) beta-blocking activity. The acid metabolite is excreted in the urine and has a half-life of about 3.7 hours.
A pharmacokinetic study was undertaken in 22 paediatric patients aged 3-16 years. A loading dose of 1000 micrograms/kg of esmolol hydrochloride was administered followed by a continuous infusion of 300 micrograms/kg/min. The observed mean total body clearance was 119 mL/kg/min, the mean volume of distribution 283 mL/kg and the mean terminal elimination half-life 6.9 min, indicating that esmolol hydrochloride kinetics in children are similar to those in adults. However, large inter-individual variability was observed.
No teratogenic effect has been observed in animal studies. In rabbits an embryo toxic effect has been observed (increase in fetal resorption) which was probably caused by esmolol hydrochloride. This effect was observed at doses at least 10 times higher than the therapeutic dose. No studies have been done on the effect of esmolol hydrochloride on the fertility and on peri- and postnatal effects. Esmolol hydrochloride was found to be not mutagenic in several in vitro and in vivo test systems. The safety of esmolol hydrochloride has not been examined in long-term studies.
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