FDA Approves Intranasal Etripamil for Type of Arrhythmia

The FDA has approved intranasal etripamil (Cardamyst; Milestone Pharmaceuticals) for the acute treatment of paroxysmal supraventricular tachycardia (PSVT), making it the first self-administered, on-demand therapy designed to treat episodes outside of a health care setting, according to an FDA news release.¹

PSVT is characterized by sudden episodes of rapid heart rate often exceeding 100 beats per minute that can cause palpitations, chest discomfort, shortness of breath, dizziness, or syncope. A single PSVT episode is typically not life-threatening, but frequent or prolonged episodes can contribute to downstream cardiac complications, including dilated cardiomyopathy.

This approval allows adults to treat episodes of abnormally fast heart rhythm using a nasal spray at symptom onset before seeing a health care provider for follow-up. Before this approval, PSVT treatment options included diltiazem, verapamil, or intravenous (IV) adenosine administered by a provider.²

“The FDA approval of CARDAMYST is a watershed moment for Milestone and a gratifying event for our team members, patients, clinical investigators, and health care providers who participated in the development program,” Joseph Oliveto, president and CEO of Milestone Pharmaceuticals, said in a news release, “all of whom I sincerely thank for their dedication, counsel, and collaboration toward this important achievement.”³

Returning to Normal Rhythm Within 30 Minutes

According to the news release, this approval was based on findings from the phase 3 RAPID trial (NCT03464019), a double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of etripamil 70-mg nasal spray using a symptom-prompted, repeat-dose regimen.⁴

Funded by Milestone Pharmaceuticals, RAPID enrolled 692 adults with a documented history of sustained, symptomatic PSVT, who were randomly assigned to receive either etripamil or placebo. Participants self-administered 1 dose at symptom onset and a second dose 10 minutes later if symptoms did not resolve. The primary end point was time to conversion of PSVT to normal heart rhythm for at least 30 seconds within 30 minutes of the first dose, adjudicated using continuous electrocardiographic monitoring (EKG).

Among patients with confirmed atrioventricular-nodal–dependent PSVT, 64% of those treated with etripamil returned to their normal heart rhythm within 30 minutes of using the spray, compared with 31% of those using placebo (HR, 2.62; 95% CI, 1.66-4.15; P < .0001). Median time to conversion was 17.2 minutes with etripamil vs 53.5 minutes with placebo.

Beyond rhythm conversion, secondary analyses showed greater improvements in patient-reported symptoms among those treated with etripamil. Compared with placebo, a significantly higher proportion of patients receiving etripamil reported improvement in rapid pulse, palpitations, shortness of breath, anxiety, and dizziness or lightheadedness following treatment; an insignificantly larger proportion saw improvements in tightness, pain, and pressure in the chest with treatment. Additionally, fewer patients in the etripamil group required additional medical interventions, such as IV antiarrhythmics.

“RAPID was not powered to detect significantly different rates between treatment groups regarding additional medical interventions and emergency department visits,” the RAPID researchers said. “Future studies will therefore be needed to confirm the potential of etripamil to decrease health-care burdens and costs.“

Etripamil Nasal Spray Safety Warnings

Safety findings were consistent with prior studies of intranasal etripamil, according to RAPID researchers. Treatment-emergent adverse events (AEs) occurred in 50% of patients receiving etripamil and 11% of those receiving placebo, with most events localized to the nasal administration site and rated as mild or moderate. The most common AEs included nasal discomfort (23%), nasal congestion (13%), rhinorrhea (9%), and epistaxis (6%). Importantly, no serious etripamil-related AEs or deaths were reported, and no cases of high-grade atrioventricular block or clinically significant bradyarrhythmias were observed on EKGs.

The FDA noted that patients with hypersensitivity to etripamil or its components, those with heart failure, and individuals with certain underlying cardiac conditions should not use the drug.¹ Because etripamil may cause dizziness or fainting, patients are advised to administer the medication while seated.

References

1. FDA approves drug for type of abnormally fast heart rhythm. News release. FDA. Updated December 15, 2025. Accessed December 16, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-type-abnormally-fast-heart-rhythm
2. Paroxysmal supraventricular tachycardia (PSVT). Cleveland Clinic. Updated October 30, 2025. Accessed December 16, 2025. https://my.clevelandclinic.org/health/diseases/22232-paroxysmal-supraventricular-tachycardia-psvt
3. 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. December 12, 2025. Accessed December 16, 2025. https://investors.milestonepharma.com/news-releases/news-release-details/milestone-receives-fda-approval-cardamysttm-etripamil-first-and
4. 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. Lancet. 2023;402(10396):118-128. doi:10.1016/S0140-6736(23)00776-6