FDA Approves First Self-Administered Nasal Spray for Adults with PSVT, Milestone Pharmaceuticals Reports

The FDA has approved etripamil nasal spray (Cardamyst) for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults, according to an announcement from Milestone Pharmaceuticals today. The approval marks the first FDA-approved treatment for PSVT in more than 30 years and introduces a prescription option that patients can self-administer outside of emergency or other health care settings, the company stated.

Etripamil is a rapid-acting intranasal calcium channel blocker (CCB) designed for use at the onset of PSVT symptoms. More than 2 million Americans are diagnosed with PSVT, an arrhythmia characterized by episodes of sudden onset tachycardia that resolves spontaneously. ² The heart rate spike is unpredictable and may last up to several hours; often it affects individuals without underlying structural heart disease.² The sequalea, eg, disabling palpitations, shortness of breath, and vertigo, can force individuals to limit daily activities.

Commonly identified triggers of PSVT include physical activity, stress, caffeinated beverages, nicotine, hyperthyroidism, myocardial ischemia, infection, hypoxia, and hypovolemia.²

"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, an etripamil investigator said in a statement. “[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.”

The company said the product is expected to be available in US retail pharmacies in the first quarter of 2026.

The Phase 3 RAPID Trial

FDA approval was based on a clinical development program that included safety data from more than 1,800 participants and more than 2,000 PSVT episodes, including the phase 3 RAPID trial, a global, randomized, double-blind comparison of [etripamil] vs placebo, published in The Lancet in 2023.

In RAPID, 64% of participants who self-administered [etripamil] (N=99) converted from SVT to sinus rhythm within 30 minutes, compared with 31% of those receiving placebo (N=85) (HR = 2.62; P <.001). At 1 hour, 73% of participants treated with [etripamil] had converted to sinus rhythm, Milestone said.

Median time to conversion for [etripamil]-treated participants was 17 minutes (95% CI, 13.4–26.5) compared with 54 minutes (95% CI, 38.7–87.3) for those receiving placebo. According to the company, reductions in time to conversion were evident early and durable.

Milestone also reported that treatment effects and safety outcomes were consistent across subgroups, including participants who were concurrently using beta blockers or CCBs.

Unmet Need in PSVT Management

Many individuals experience recurrent episodes of PSVT that require treatment on an annual basis. Although episodes can be treated with oral CCBs and/or beta blockers, effective treatment has generally required intravenous CCB therapy administered in health care settings, contributing to emergency department utilization and associated costs. For those with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or susceptibility to dehydration, the post-attack morbidity can be significant, according to the Milestone statement.

Safety and Label Warnings

The most frequent adverse events (AEs) reported in randomized clinical trials, occurring in 5% or more of participants, were described as mild to moderate and transient. These included local-site nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis. Less than 2% of trial participants discontinued treatment because of adverse events.

Prescribing information includes warnings related to fainting due to effects on blood pressure, heart rate, and cardiac electrical activity. [Etripamil] is contraindicated in adults with moderate to severe heart failure, Wolff-Parkinson-White syndrome, sick sinus syndrome without a permanent pacemaker, second-degree or higher atrioventricular block, or known hypersensitivity to the product or its components.

Future development in AFib-RVR

The company also indicated that FDA approval in PSVT enables continued development of etripamil for atrial fibrillation with rapid ventricular rate (AFib-RVR) under a supplemental new drug application pathway. The company plans to initiate a phase 3 registrational program informed by the ReVeRA phase 2 trial, which was published in Circulation: Arrhythmia and Electrophysiology.

An estimated 10 million Americans have atrial fibrillation. Milestone’s market research suggests that 30% to 40% of patients with AFib experience one or more symptomatic episodes of RVR per year that require treatment, corresponding to a potential addressable population of approximately 3 to 4 million patients by 2030, according to the company.

References

1. Milestone receives FDA approval of CARDAMYST (etripamil), a self-administered nasal spray for adults with paroxysmal supraventricular tachycardia. News release. Milestone Pharmaceuticals. December 15, 2025. Accessed December 15, 2025.

2. Hafeez Y, Quintanilla Rodriguez BS, Ahmed I, Grossman SA. Paroxysmal supraventricular tachycardia. StatPearls [inthttps://www.ncbi.nlm.nih.gov/books/NBK507699/ernet]. Updated February 28, 2024. Accessed December 15, 2025.