Intranasal Calcium Channel Blocker for Paroxysmal Supraventricular Tachycardia

Paroxysmal supraventricular tachycardia (PSVT) is an arrhythmia that presents as intermittent episodes of rapid heart rate with sudden onset and spontaneous termination. Common symptoms of PSVT include shortness of breath, dizziness, chest pain, and syncope, which can lead to complications such as tachycardia-induced cardiomyopathy, signs and symptoms of heart failure, and myocardial ischemia, especially in older patients and in those with underlying structural heart diseases.¹

On December 12, 2025, the FDA approved etripamil (Cardamyst), an intranasal calcium channel blocker developed by Milestone Pharmaceuticals Inc. Etripamil is used to convert acute symptomatic episodes of PSVT to sinus rhythm in adults, offering a portable and fast-acting self-treatment option for patients.²

Efficacy

Approval of etripamil was supported by the results from the phase 3 RAPID trial (NCT03464019), a double-blind, placebo-controlled study that enrolled 692 patients with a history of sustained PSVT episodes. Patients were randomly assigned 1:1 to self-administer etripamil 70 mg or placebo during episodes of perceived PSVT, with a second dose self-administered if symptoms persisted 10 minutes after the first dose.²

Etripamil demonstrated superior efficacy compared with placebo for converting PSVT to sinus rhythm, with 64% of patients in the etripamil group and 31% in the placebo group converting to sinus rhythm for at least 30 seconds within 30 minutes after the first dose (HR, 2.62; 95% CI, 1.66-4.15; P < .0001).^2,3 The etripamil regimen had a median time to conversion of 17.2 minutes (95% CI, 13.4-26.5) vs 53.5 minutes (95% CI, 38.7-87.3) for placebo.^2,3 The investigators concluded that etripamil provided an effective self-treatment option for the conversion of PSVT to sinus rhythm outside of a health care setting.³

Safety

Etripamil is generally well tolerated and has demonstrated minimal adverse events (AEs) during clinical trials. The most common AEs were nasal discomfort (23%), nasal congestion (14%), rhinorrhea (17%), increased lacrimation (17%), throat irritation (14%), sneezing (9%), nasal pruritus (6%), and headache (6%).^2,3 No serious AEs or deaths related to etripamil treatment were reported.^2,3 AEs occurred in 50% of patients receiving etripamil and 11% of patients receiving placebo, with most AEs at the administration site.^2,3 All AEs were transient and resolved without intervention.^2,3

Due to the drug’s cardiac and blood pressure effects, etripamil carries a warning for syncope. If this occurs, patients should lie down and receive supportive treatment. To minimize fall risk, patients should be seated for administration.²

Dosing and Administration

Etripamil is available as a self-administered nasal spray. Each device contains 2 sprays for a total of 70 mg. Patients should self-administer a dose of 70 mg (1 spray in each nostril) as soon as possible after PSVT symptom onset. If symptoms do not resolve after 10 minutes, a second dose of 70 mg may be administered. Patients who do not experience symptom improvement within 20 minutes after the second dose must seek emergency medical help. The maximum dose of etripamil in a 24-hour period is 140 mg. The product should be stored at room temperature and should not be test sprayed or primed before use.²

REFERENCES

1. Hafeez Y, Quintanilla Rodriguez BS, Ahmed I, Grossman SA. Paroxysmal Supraventricular Tachycardia. In: StatPearls [Internet]. StatPearls Publishing; January 2026. Accessed June 24, 2026. https://www.ncbi.nlm.nih.gov/books/NBK507699/

2. Cardamyst. Prescribing information. Milestone Pharmaceuticals Inc; 2025. Accessed March 5, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218571s000lbl.pdf

3. Stambler BS, Camm AJ, Alings M, et al; RAPID Investigators. 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