Etripamil Becomes First, Only Self-Administered Nasal Spray Approved for PSVT

The FDA has approved etripamil (Cardamyst; Milestone Pharmaceuticals), the first and only self-administered nasal spray for adults with paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm, according to a news release from Milestone Pharmaceuticals. The approval gives patients with PSVT a novel, effective treatment that can be self-administered outside of health care settings.¹

What is PSVT?

PSVT is a form of arrhythmia that occurs when a short-circuit rhythm develops in the upper chamber of the heart, resulting in a rapid heartbeat that can start and start abruptly. It can impair a patient’s heart function, leading to symptoms like shortness of breath or lightheadedness. Other symptoms may include heart palpitations, weakness or fatigue, chest pain, or fainting; given the sudden onset of symptoms, episodes can sometimes be mistaken for panic attacks.^1,2

Uncertainty as to when one may be afflicted with a PSVT episode can cause anxiety and negatively impact the day-to-day activities of patients with the condition. Patients with underlying cardiovascular or medical conditions, including obstructive coronary disease, dehydration, and heart failure, face heightened impact and morbidity from PSVT attacks. With a lack of available treatment options, patients are often forced to admit themselves to the emergency department and undergo costly procedures.¹

What Did Etripamil Investigators Find?

Etripamil is a rapid-acting calcium channel blocker that helps patients treat symptomatic and unpredictable episodes of PSVT. Its approval was based on positive results from the global, randomized, double-blind phase 3 RAPID trial (NCT03464019), which was deemed part 2 of the NODE-301 study. Patients were screened and enrolled between October 2020 and July 2022; a total of 706 were included in the trial, of which 692 (98%) tolerated the test dose and were randomly assigned. ^1,3,4

Among those randomly assigned, 437 had no PSVT episode; for the rest of the population—patients who were perceived to have experienced an episode of PSVT, constituting the safety population—135 were randomized to the etripamil group and 120 were randomized to placebo. For the efficacy population—including those who self-administered the blinded study drug for an episode of PSVT that was confirmed to be atrioventricular-nodal-dependent—99 patients self-administered the etripamil regimen, and 85 patients self-administered the placebo regimen.^1,3

Kaplan-Meier analyses were conducted to determine the incidence of the primary efficacy outcome, which was conversion from atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm up to 30 minutes and for at least 30 seconds. In the efficacy population, the primary outcome occurred in 63 (64%) of 99 patients in the etripamil group and 26 (31%) of 85 patients in the placebo group (hazard ratio [HR]: 2.62; 95% CI, 1.66–4.14; P < .0001). The median time to conversion was 17.2 minutes (95% CI, 13.4–26.5) with the etripamil regimen compared with 53.5 minutes (95% CI, 38.7–87.3) with placebo, according to the investigators.³

Analyses of efficacy in predefined subpopulations found little differences in HRs between groups. These groups included patients with a duration of 30 minutes or less versus more than 30 minutes between symptom onset and drug administration and subgroups based on age and the concomitant use of cardiac medications, including calcium-channel blockers and β blockers.³

A series of secondary outcomes were assessed. Given the first assessment did not meet significance, the following assessments were reported as exploratory. There were lower percentages of patients seeking additional medical interventions and emergency department visits in the etripamil group compared with the placebo group. Furthermore, patients treated with etripamil demonstrated symptomatic improvements compared with those treated with placebo. Patients treated with etripamil compared with placebo reported significantly greater reductions in rapid pulse, palpitations, anxiety, shortness of breath, and feeling dizzy or light-headed.³

Importantly, etripamil was well-tolerated when administered in a non-health care setting during a PSVT episode. Common treatment-emergent adverse events were localized to the nasal administration site and were transient and mild in nature. There were no serious adverse events that occurred within 24 hours after etripamil administration.³

“Some people with PSVT have endured years of anxiety, fearing their next episode and the stress and disruption of emergency department visits,” James Ip, MD, FACC, FHRS, an etripamil investigator, said in the news release. “Etripamil will give many of them the ability to administer a medication themselves that can quickly stop their PSVT episode and potentially avoid a hospital trip or a call to emergency services.”¹

REFERENCES

1. Milestone receives FDA approval of CARDAMYST (etripamil) as first and only self-administered nasal spray for adults with paroxysmal supraventricular tachycardia (PSVT). News Release. Milestone Pharmaceuticals. Released December 15, 2025. Accessed December 15, 2025. https://investors.milestonepharma.com/news-releases/news-release-details/milestone-receives-fda-approval-cardamysttm-etripamil-first-and

2. Paroxysmal supraventricular tachycardia (PSVT). John Hopkins Medicine. Accessed December 15, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/paroxysmal-supraventricular-tachycardia

3. Stambler BS, Camm AJ, Alings M, et al. Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial. The Lancet. 2023;402(10396):118-128. doi:10.1016/S0140-6736(23)00776-6

4. Efficacy and safety of etripamil for the termination of spontaneous paroxysmal supraventricular tachycardia (PSVT). (NODE-301). ClinicalTrials.gov Identifier: NCT03464019. Last Updated July 12, 2024. Accessed December 15, 2025. https://clinicaltrials.gov/study/NCT03464019