Landiolol: A Review of its use in Intraoperative and Postoperative Tachyarrhythmias

Abstract

Landiolol (Onoact(®)) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). In patients undergoing surgical procedures, landiolol 0.125 mg/kg/min for 1 min followed by 0.04 mg/kg/min for 10 min was superior to placebo in improving intraoperative tachycardia in randomized double-blind trials. The beneficial effects of landiolol in attenuating adverse haemodynamic or other changes that can occur during surgery or invasive procedures (e.g. percutaneous coronary intervention) have been demonstrated in a large number of randomized controlled trials. For example, several studies showed that landiolol attenuated the increase in heart rate associated with tracheal intubation, without adversely affecting blood pressure or other haemodynamic parameters. Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition)

“…Furthermore, a patient with thyroid storm and bronchial asthma was successfully managed with esmolol [144]. Landiolol, an ultra-short-acting beta1-selective AA with a t1/2 of 3-4 minutes and approximately 8-fold greater beta1-selectivity than esmolol, has been approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias [145]. Landiol was recently approved for the treatment of tachyarrhythmias in other situations, which strongly suggests that it is useful for the treatment of tachyarrhythmias in thyroid storm.…”

Comparison of the -Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions

“…The volume of distributionassessed in human subjects-reflects the difference in permeation. Its size was found to be more than an order of magnitude larger for esmolol (V D 5 3.43 l/kg; Sum et al, 1983) than for landiolol (V D 5 0.16 -0.24 l/kg; Murakami et al, 2005;Plosker, 2013).…”

“…It is worth pointing out that this difference in pharmacochaperoning activity is probably of clinical relevance: Continuous infusion of therapeutically relevant doses of landiolol results in concentrations in plasma of about 1-4 mM (Murakami et al, 2005;Plosker, 2013). Given its small apparent volume of distribution, landiolol is not enriched within the intracellular compartment.…”

“…Landiolol is a short-acting b-adrenergic receptor antagonist that has a half-life (3-4 minutes) shorter than the reference compound esmolol (9 minutes) (Plosker, 2013). Cleavage of an ester bond generates the major landiolol metabolite, M1, which has a half-life (1.8 hours) substantially longer than the parent compound (Murakami et al, 2005).…”

“…In fact, the ratio of half-lives predicts that under steady-state conditions, the concentration of M1 may exceed that of landiolol by several fold. It was therefore of interest to document the affinity and selectivity of M1 for human b 1 -and b 2 -adrenergic receptors and to compare it to that of the parent compound, for which the affinity is quoted in reviews, (e.g., Plosker, 2013), but for which the original data are inaccessible.…”