Medical Policy:

12.01.096-001

Topic:

Cardamyst

Section:

Injections

Effective Date:

August 10, 2026

Issued Date:

June 3, 2026

Last Revision Date:

June 2026

Annual Review:

February 2027

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Cardamyst™ (etripamil) Nasal spray	Conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults		1

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member's benefit plan.

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
PA	Target Agent(s) will be approved when ALL of the following are met: 1. The patient has ONE of the following: A. A diagnosis of paroxysmal supraventricular tachycardia (PSVT) AND BOTH of the following: 1. A history of sustained PSVT episodes lasting 20 minutes or longer AND 2. Previous PSVT episodes were confirmed by electrocardiogram OR B. Another FDA labeled indication for the requested agent and route of administration OR C. An indication that is supported in compendia for the requested agent and route of administration AND 2. If the patient has an FDA labeled indication, then ONE of the following: A. The patient's age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient's age for the requested indication AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, electrophysiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The patient does NOT have any FDA labeled contraindications to the requested agent Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Module

Clinical Criteria for Approval

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has ONE of the following:

A. A diagnosis of paroxysmal supraventricular tachycardia (PSVT) AND BOTH of the following:

1. A history of sustained PSVT episodes lasting 20 minutes or longer AND

2. Previous PSVT episodes were confirmed by electrocardiogram OR

B. Another FDA labeled indication for the requested agent and route of administration OR

C. An indication that is supported in compendia for the requested agent and route of administration AND

2. If the patient has an FDA labeled indication, then ONE of the following:

A. The patient's age is within FDA labeling for the requested indication for the requested agent OR

B. There is support for using the requested agent for the patient's age for the requested indication AND

3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, electrophysiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND

4. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS

Module	Ops Set Up	Validation Options	Other Explanation
PA	Validation: Apply Baseline and go to Validation Options	Age Verification;Diagnosis

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
Universal QL	Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: 1. The requested quantity (dose) does NOT exceed the program quantity limit OR 2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: A. BOTH of the following: 1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication OR B. BOTH of the following: 1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND 2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR C. BOTH of the following: 1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months

Module

Clinical Criteria for Approval

Universal QL

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR

2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:

A. BOTH of the following:

1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND

2. There is support for therapy with a higher dose for the requested indication OR

B. BOTH of the following:

1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND

2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR

C. BOTH of the following:

1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND

2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS

Module	Ops Set Up	Validation Options	Other Explanation
Universal QL	Validation: Apply Baseline and go to Validation Options

Reference to Our Policy Information Guidelines

CLINICAL RATIONALE

Guidelines

Guidelines do not currently address use with Cardamyst. The 2015 American College of Cardiology/American Heart Association/Heart Rhythm Society Guideline for the management of adult patients with supraventricular tachycardia (SVT) categorizes recommendations into acute treatment and ongoing management of SVT with an unknown mechanism.(3)

Acute management of regular SVT begins with vagal maneuvers (Class I) and/or IV adenosine (Class I). If vagal maneuvers are ineffective or not feasible, synchronized cardioversion (Class I) is recommended for patients who are hemodynamically unstable. If the patient is hemodynamically stable, IV beta blockers or IV non-dihydropyridine calcium channel blockers are recommended (Class IIa) followed by synchoronized cardioversion (Class I) if the IV medications are ineffective or not feasible.(3)

Ongoing (chronic) management should include patient preferences along with clinical judgment. Recommendations for treatment options (drug therapy, ablation, or observation) must be considered in the context of frequency and duration of the SVT, along with clinical manifestations, such as symptoms or adverse consequences (e.g., development of cardiomyopathy). Electrophysiology (EP) study with catheter ablation (Class I) is the first-line therapy as it offers a potentially curative option. In patients who are not candidates for, or decline ablation, oral beta‑blockers, diltiazem, or verapamil are recommended (Class I) (in the absence of ventricular pre‑excitation). Flecainide or propafenone may be used in patients without structural heart disease or ischemic heart disease (Class IIa). Amiodarone, dofetilide, sotalol, and digoxin are additional pharmacotherapy options (Class IIb).(3)

Efficacy

Cardamyst was evaluated in RAPID (NCT03464019), a phase III, multicenter, randomized, double‑blind, placebo‑controlled trial evaluating Cardamyst 70 mg nasal spray for the acute, self‑administered treatment of paroxysmal supraventricular tachycardia (PSVT) in 692 adults outside of a healthcare setting. Key inclusion criteria included adults with a history of PSVT with sustained, symptomatic episodes greater than or equal to 20 minutes as documented by electrocardiogram and the ability to recognize symptomatic PSVT episodes, suitability for outpatient self‑administration. Patients also underwent supervised test dosing to assess tolerability before randomization. Participants self‑administered Cardamyst or placebo at the onset of a perceived PSVT episode, with optional redosing if symptoms persisted. The primary efficacy endpoint was the proportion of positively adjudicated PSVT episodes converting to sinus rhythm within 30 minutes after dosing. RAPID showed that approximately 64% of etripamil‑treated patients converted to sinus rhythm within 30 minutes compared with about 31% with placebo, with a median time to conversion of 17.2 minutes versus 53.5 minutes, respectively, demonstrating significantly faster and more frequent conversion with Cardamyst. The treatment was generally well tolerated, with mostly mild, transient nasal adverse events and no serious etripamil‑related safety signals, supporting Cardamyst as an effective, rapid, on‑demand, patient‑controlled therapy for acute PSVT outside of a health care setting.(1,2)

Safety

Cardamyst is contraindicated in patients with:(1)

· Hypersensitivity to Cardamyst or any of its components

· Heart failure – New York Heart Association (NYHA) Class II to IV

· Wolff-Parkinson-White (WPW), Lown-Ganong-Levine (LGL) syndromes, or manifest pre-excitation (delta wave) on a 12-lead electrocardiogram (ECG)

· Sick sinus syndrome without a permanent pacemaker

· Second degree atrioventricular (AV) Mobitz 2 block or higher degree of AV block

REFERENCES

Number	Reference
1	Cardamyst prescribing information. Milestone Pharmaceuticals USA, Inc. December 2025.
2	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
3	Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the management of adult patients with supraventricular tachycardia: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016;133(14):e506‒e574. doi:10.1161/CIR.0000000000000311

Professional Statements and Societal Positions Guidelines

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Final Module	Target Agent GPI	Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Targeted NDCs When Exclusions Exist	Final Age Limit	Preferred Status	Effective Date

	340000110020	Cardamyst	etripamil nasal soln	70 MG/DOSE	M ; N ; O ; Y

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Agent GPI	Target Brand Name(s)	Target Generic Name(s)	Strength	QL Amount	Dose Form	Days Supply	Duration	Targeted NDCs When Exclusions Exist	Age Limit	Effective Date	Term Date

34000011002030	Cardamyst	etripamil nasal soln	70 MG/DOSE	3	Cartons	180	Days

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Client Formulary

Cardamyst	etripamil nasal soln	70 MG/DOSE	Commercial ; HIM ; WY NetR-Commercial Custom

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary

Cardamyst	etripamil nasal soln	70 MG/DOSE	Commercial ; HIM ; WY NetR-Commercial Custom

Place of Service: Inpatient/Outpatient

The policy position applies to all commercial lines of business

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