Paroxysmal Supraventricular Tachycardia (PSVT) Treatments

CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults.

Nasal Spray: Clear colorless to yellow solution. 70 mg of etripamil per device.

CARDAMYST is contraindicated in patients with:

The following clinically significant adverse reactions are described elsewhere in the labeling:

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.

Etripamil, the active ingredient of CARDAMYST is a calcium channel blocker.

The chemical name of etripamil is benzoic acid, 3-[2-[[(4S)-4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]methylamino]ethyl]-, methyl ester.

Its molecular weight is 452.59 and its molecular formula is C

The structural formula is:

Etripamil is a colorless to slightly yellow oil. Etripamil has a pKa of 8.57 and is very soluble in methyl tert-butyl ether, freely soluble in methanol, dichloromethane and acetone, sparingly soluble in ethanol and hexane, and insoluble in water.

CARDAMYST is a spray intended for nasal administration. Each device of CARDAMYST delivers two metered sprays of etripamil with a total of 70 mg. CARDAMYST contains 350 mg/mL of etripamil and the following inactive ingredients: acetic acid, edetate disodium, sulfuric acid for pH adjustment, and water for injection.

The RAPID study (NCT #03464019) was a randomized, double-blind, placebo-controlled, multicenter, event-driven, phase 3 study designed to evaluate the efficacy and safety of CARDAMYST in patients with a history of symptomatic PSVT. Six hundred ninety-two (692) patients were randomized 1:1 to CARDAMYST 70 mg or placebo. Patients with an episode of perceived PSVT were to self-administer the study drug intranasally in a medically unsupervised setting and self-administer a second dose of the study drug if symptoms persisted at 10 minutes after the first dose. Continuously obtained electrocardiographic data during the episode of PSVT were blindly adjudicated. The primary endpoint was time-to-conversion of confirmed PSVT to sinus rhythm for at least 30 seconds within 30 minutes of the first dose.

Of the 692 randomized patients, 255 patients perceived an episode of PSVT and self-administered the study drug; 184 (72%) episodes were confirmed by blinded adjudication to be PSVT. Patients had a median age of 54 years (range 19 to 78 years) and were 71% female, 93% Caucasian, 3% Black and 4% other. Sixty-three percent (63%) of patients with confirmed PSVT episode were taking concomitant beta blocker or calcium channel blocker.

In the study's primary analysis, patients with confirmed episodes of PSVT, Kaplan-Meier Estimates of those who converted to sinus rhythm within 30 minutes were 64% and 31% for CARDAMYST and placebo, respectively, with a hazard ratio of 2.6 [95% CI: (1.7, 4.2)], p-value <0.001. Median time-to-conversion was 17.2 minutes (95% CI: 13.4, 26.5) with CARDAMYST versus 53.5 minutes (95% CI: 38.7, 87.3) with placebo. Kaplan-Meier estimates of conversion remained in favor of CARDAMYST at 300 minutes; hazard ratio 1.7 [95% CI: (1.2, 2.4)].

Kaplan-Meier plot of estimated probabilities of achieving sinus rhythm following treatment with CARDAMYST are shown in

1) 71/255 (28%) patients who self-administered CARDAMYST for a perceived episode of PSVT did not have confirmed PSVT and are excluded.

Seventy-one (71) of 255 (28%) patients who self-administered CARDAMYST for a perceived episode of PSVT did not have PSVT confirmed due to missing ECG data (4%), resolution of PSVT prior to dosing (5%), or other rhythm diagnoses (19%). In an analysis assuming all 71 of these patients did not convert, the Kaplan-Meier estimates for conversion to sinus rhythm within 30 minutes were 50% and 23% for the CARDAMYST and placebo groups, respectively, with a hazard ratio of 2.6 [95% CI: (1.6, 4.1)].

In RAPID, the results for the primary efficacy endpoint were generally consistent across major subgroups including geographic region, sex, age group, concomitant medications, and duration from onset of symptoms to first dose (

Advise the patient to read the FDA-approved patient labeling (