Etripamil

Etripamil is an L-type calcium influx inhibitor (slow channel blocker or calcium ion antagonist). Etripamil exerts its pharmacologic effect by modulating the influx of ionic calcium across the cell membrane of the AV nodal cells as well as arterial smooth muscles and contractile myocardial cells.

• CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. CARDAMYST is a calcium channel blocker indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults ( 1 ).

• CARDAMYST is contraindicated in patients with: Hypersensitivity to CARDAMYST or any of its components. Heart failure – New York Heart Association (NYHA) Class II to IV.contraindicated

For intranasal use only ( 2.1 ). Initial dosage: A dose of 70 mg is administered as two nasal sprays, one spray into each nostril. Each nasal spray device delivers two sprays. The two sprays together contain a total of 70 mg etripamil ( 2.1 ). Repeat dosage (if needed): Should symptoms persist for 10 minutes after administration of CARDAMYST, take a second dose of 70 mg administered as two nasal sprays, one spray into each nostril. Do not exceed 140 mg in a 24-hour period ( 2.1 ). 2.1 Recommended Dosage Administer as soon as possible after PSVT symptom onset. Administer CARDAMYST by the nasal route only. Each CARDAMYST device delivers two sprays for a total of 70 mg. Recommended Dosage: Using one nasal spray device, administer one spray into each nostril for a total initial dose of 70 mg. If symptoms persist after 10 minutes, use the second nasal spray device to administer a second dose of one spray into each nostril (70 mg total). Patients and caregivers should call their healthcare provider or seek emergency medical help if symptoms do not improve within 20 minutes after a second dose. Do not exceed 140 mg in a 24-hour period. See Instructions for Use for proper nasal spray technique. If a full initial dose (i.e., 2 sprays, one in each nostril) is not administered due to device malfunction or misuse, the patient should wait at least 10 minutes before self-administering a second dose, if needed.

Syncope: May cause dizziness and/or syncope, especially in patients with a history of syncope. Administer in a sitting position ( 5.1 ). 5.1 Syncope Related to Hemodynamic Effects Because of effects on blood pressure, heart rate, and cardiac conduction, CARDAMYST may cause dizziness and/or syncope, especially in patients with a history of syncope and high-grade AV block or sinus node dysfunction, or those with a history of syncope during an episode of PSVT. In clinical trials, a small percentage of patients (0.4%) experienced clinically significant hypotension during test dosing prior to randomization, which precluded further participation in the study. Patients with a history of hypotensive episodes or those at increased risk for hemodynamic instability should be monitored appropriately when initiating CARDAMYST. If syncope occurs, patients should be placed in the recumbent position and treated supportively. Patients should be cautioned about these possible adverse effects and advised to administer CARDAMYST in a sitting position, and in a location where the risk of fall is minimal.

The following clinically significant adverse reactions are described elsewhere in the labeling: Risk of syncope [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (incidence > 5%) are nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Milestone Pharmaceuticals USA, INC. at toll-free phone 1-877-207-4764 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of CARDAMYST was evaluated using pooled data from double-blind, randomized, placebo-controlled trials including NODE-1, NODE-301 Part 1, RAPID, and RAPID Extension. A total of 321 patients were treated with CARDAMYST in randomized controlled studies. In the RAPID and RAPID Extension studies, in which patients had the option of self-administering a second dose of CARDAMYST for a perceived episode of PSVT, the majority of patients (65%) self-administered a second dose of CARDAMYST (2x70mg). In NODE-301 Part 1, RAPID, and RAPID Extension, to assess tolerability, a test dose(s) was given prior to randomization. A small percentage of patients failed the test dose due to hypotension (0.4%) [see Warnings and Precautions ( 5.1 )].

Lactation: A lactating woman should pump and discard breastmilk for 12 hours after CARDAMYST administration ( 8.2 ). 8.1 Pregnancy Risk Summary There are no available data on the use of CARDAMYST during pregnancy to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Reproductive studies conducted with intravenous administration of etripamil in pregnant rats and rabbits during organogenesis did not show any evidence of fetal harm or malformations in rats at exposures up to approximately 3x the maximum concentration (C max ) and 0.4x the AUC at the maximum recommended human dose (MRHD) and in rabbits at exposures approximately equivalent to the C max and 10x the AUC at the MRHD, at which maternal toxicities were observed (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Metabolism

After one 70 mg dose of etripamil, mean (%CV) area under the concentration-time curve (AUC) is approximately 5461 (51.6%) ng*min/mL and the C max is approximately 99 (64.6%) ng/mL. After a second 70 mg dose of etripamil administered 10 minutes after the first dose, mean (%CV) AUC is approximately 7721 (50.3%) ng*min/mL and the C max is approximately 132 (59.1%) ng/mL.

Overdosage is expected to cause peripheral vasodilation with possible symptomatic hypotension and reflex tachycardia. AV block and /or pauses may also occur. Treatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow calcium channel. Clinically significant hypotensive reactions or high degree AV block should be treated with fluid administration or vasopressor agents, or cardiac pacing, respectively. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. It is unknown whether etripamil is dialyzable. However, the structurally related compound, verapamil cannot be removed by hemodialysis.

• Dec 12, 2025NDANDA218571Milestone Pharms Usa

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Etripamil as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Etripamil Nasal Spray in Patients With Paroxysmal Supraventricular Tachycardia
  Completed · Phase 3 · Interventional · 130 enrolled · Milestone Pharmaceuticals Inc.
  NCT04952610updated 2026-05-15
• ReVeRA-301: Etripamil in Atrial Fibrillation Phase 3
  Not yet recruiting · Phase 3 · Interventional · 750 enrolled · Milestone Pharmaceuticals Inc.
  NCT06716021updated 2026-01-14
• The NODE-202 Study (Study of Etripamil Nasal Spray in Pediatric Patients)
  Recruiting · Phase 2 · Interventional · 60 enrolled · Milestone Pharmaceuticals Inc.
  NCT05763953updated 2025-08-01
• Efficacy and Safety Study of Etripamil Nasal Spray Self-Administration for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia
  Completed · Phase 3 · Interventional · 500 enrolled · Corxel Pharmaceuticals
  NCT05410860updated 2024-12-24
• Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia (PSVT). NODE-302
  Terminated · Phase 3 · Interventional · 169 enrolled · Milestone Pharmaceuticals Inc.
  NCT03635996updated 2024-11-05
• ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2
  Completed · Phase 2 · Interventional · 69 enrolled · Milestone Pharmaceuticals Inc.
  NCT04467905updated 2024-09-19
• Efficacy and Safety of Etripamil for the Termination of Spontaneous Paroxysmal Supraventricular Tachycardia (PSVT).
  Terminated · Phase 3 · Interventional · 1,097 enrolled · Milestone Pharmaceuticals Inc.
  NCT03464019updated 2024-07-12
• Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303
  Completed · Phase 3 · Interventional · 1,116 enrolled · Milestone Pharmaceuticals Inc.
  NCT04072835updated 2024-05-23
• A Study of Etripamil in Healthy Subjects
  Completed · Phase 1 · Interventional · 12 enrolled · Corxel Pharmaceuticals
  NCT05511870updated 2023-04-10
• Efficacy and Safety of Intranasal MSP-2017 (Etripamil) for the Conversion of PSVT to Sinus Rhythm
  Completed · Phase 2 · Interventional · 199 enrolled · Milestone Pharmaceuticals Inc.
  NCT02296190updated 2020-12-30

Frequently asked questions

How does Etripamil work?

Etripamil is an L-type calcium influx inhibitor (slow channel blocker or calcium ion antagonist). Etripamil exerts its pharmacologic effect by modulating the influx of ionic calcium across the cell membrane of the AV nodal cells as well as arterial smooth muscles and contractile myocardial cells.

What is Etripamil used for?

According to FDA labeling, Etripamil carries indications including: CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. CARDAMYST is a calcium channel blocker indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Etripamil?

Etripamil is classified as Phenylalkylamine derivatives, L-Calcium Channel Receptor Antagonists, Negative Chronotropy.

What are the brand names for Etripamil?

Etripamil is marketed under brand names including Cardamyst.

What are the contraindications for Etripamil?

Etripamil labeling lists contraindications including: CARDAMYST is contraindicated in patients with: Hypersensitivity to CARDAMYST or any of its components. Heart failure – New York Heart Association (NYHA) Class II to IV.. Always consult the full prescribing information and a clinician.