A Novel Calcium Channel Blocker: Etripamil

Abstract

Symptomatic paroxysmal cardiac arrhythmias are common cardiac conditions that lead to a decreased quality of life, increased healthcare costs, and significant morbidity. Many cardiac arrhythmias increase in frequency with age, and as the elderly population continues to increase, so will the incidence and prevalence of cardiac arrhythmias. The long-term treatment options for patients with paroxysmal arrhythmias include ablation procedures and daily oral antiarrhythmics. Acute management entails vagal maneuvers, intravenous antiarrhythmics, and synchronized cardioversion. However, there are limited treatment options for patients with less frequent and less severe arrhythmias, ablation refractory disease, or who are poor candidates for ablative procedures, For abortive therapy, oral anti-arrhythmic medications are ineffective due to their slow onset of action and intravenous medications require treatment at an acute care facility, which is both costly and stressful to the patient. Etripamil is a novel intranasal non-dihydropyridine calcium channel blocker that has begun phase III clinical trials for the treatment of paroxysmal supraventricular tachycardias. Due to its intranasal mode of delivery, etripamil has a rapid onset of action, and could feasibly be administered by the patient themselves. Clinical phase II trials of etripamil in moderate to high doses demonstrated efficacy comparable to the standard of care, and took an average of 3 minutes from drug administration to conversion to sinus rhythm. In this article, we have conducted an extensive literature review of intranasal drug delivery, calcium channel blockers, and etripamil, to discuss the future possibilities of using this new medication.

Nose-to-Heart Approach: Unveiling an Alternative Route of Acute Treatment

“…Many cardiac arrhythmias become more frequent with advancing age, while the treatment options include interventional procedures (ablation, pacemaker implantation maze procedure) or daily oral antiarrhythmics [71]. Additionally, vagal maneuvers, intravenous antiarrhythmics, and synchronized cardioversion can be employed for acute treatment of tachyarrhythmias [72]. Oral beta-blockers and non-dihydropyridines CCBs can be self-administered as a "pill-inthe-pocket" approach for acute treatment of repeated episodes of recognized arrhythmias with an average time of 30 min or more [73].…”

“…Oral verapamil has been suggested as a second-line therapy for rate control in atrial fibrillation [76], cardiac extra-systolic arrhythmia alone or combined with class IC or III antiarrhythmic drugs [77]. The efficacy of IN verapamil has been tested in a dog model, while a pharmacokinetic study in rabbits revealed that the IN delivery leads to higher bioavailability compared to the oral route [72,78]. However, IN verapamil in humans resulted in almost 16.1% absolute bioavailability, attributed to dose ingestion through the nasopharynx [72,79].…”

“…The efficacy of IN verapamil has been tested in a dog model, while a pharmacokinetic study in rabbits revealed that the IN delivery leads to higher bioavailability compared to the oral route [72,78]. However, IN verapamil in humans resulted in almost 16.1% absolute bioavailability, attributed to dose ingestion through the nasopharynx [72,79].…”

Intranasal etripamil for rapid treatment of paroxysmal supraventricular tachycardia

“…Hence, there is a clear gap for a medical therapy that can provide safe, rapid, and efficacious termination of PSVT in the outpatient setting. The intranasal route is a compelling option because the posterior nasal mucosa is well suited to rapid drug absorption [ 13 ].…”

“…This leaves a relatively homogenous group, consisting of younger patients with mostly AVNRT and structurally normal hearts who are able and willing to use an intranasal medication and prefer this over tablets or ablation. It may be telling that several other intranasal therapies for cardiac conditions have been tested, such as nifedipine, nitroglycerine, and propranolol [ 13 ], and none of these are in routine use today.…”