Etripamil
FDA Drug Information • Also known as: Cardamyst
- Brand Names
- Cardamyst
- Route
- NASAL
- Dosage Form
- SPRAY
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION 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 27 H 36 N 2 O 4 . 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. Structural Formula
What Is Etripamil Used For?
1 INDICATIONS AND USAGE 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 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION 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.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 )]. The majority of treatment-related adverse reactions reported in clinical studies with CARDAMYST have been related to local reactions to, at, or near the nasal administration site, including the nose, throat, and eyes. These local reactions included nasal discomfort, nasal congestion, throat irritation, oropharyngeal pain, lacrimation, rhinorrhea, bleeding from the nose, upper-airway cough syndrome, and sneezing. Table 1: Most frequent (≥5.0%) Adverse Reactions 1 Observed in Randomized Controlled Studies 1) Adverse reactions that occurred within 24 hours of study drug administration (TEAE24h) for perceived PSVT in the double-blind, placebo-controlled studies, NODE-1, NODE-301 Part 1, RAPID and RAPID Extension that had an overall incidence of 5% or greater and where the incidence is at least 1% greater than the placebo group. 2) 2x70 mg: first administration of etripamil 70 mg followed by a second dose of etripamil 70 mg 10 minutes later if symptoms persisted. Placebo N=223 % CARDAMYST 70 mg N=235 % CARDAMYST 2x70 mg 2 N=86 % Nasal Discomfort 6 28 23 Nasal Congestion 1 14 12 Rhinorrhea 2 12 10 Throat Irritation 1 7 6 Epistaxis 1 6 7
Contraindications
4 CONTRAINDICATIONS 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. 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. Hypersensitivity to CARDAMYST or any of its components ( 4 ). Heart failure - New York Heart Association (NYHA) Class II to IV ( 4 ). Wolff-Parkinson-White (WPW), Lown-Ganong-Levine (LGL) syndromes, or manifest pre-excitation (delta wave) on a 12-lead ECG ( 4 ). Sick sinus syndrome (except in patients with a permanent pacemaker) ( 4 ) Second degree atrioventricular (AV) Mobitz 2 block or higher degree of AV block ( 4 )
Pregnancy and Breastfeeding
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. Data Animal Data In pregnant rats, intravenous administration of etripamil throughout the period of organogenesis did not result in any adverse effects on embryofetal development at doses up to 0.375 mg/kg/day, approximately 3x the C max and 0.4x the AUC at the MRHD. In pregnant rabbits, intravenous administration of etripamil throughout the period of organogenesis did not result in embryofetal abnormalities at doses up to 0.1 mg/kg/day, approximately equivalent to the C max and 10x the AUC at the MRHD. Abortion in one animal was noted at the high dose of 0.1 mg/kg/day, a dose that caused maternal toxicity. In the pre- and post-natal toxicity study in rats, intravenous administration of etripamil from gestation day 7 through the lactation period (post-partum day 20), did not show any adverse effects on pre- and postnatal development at doses up to 0.374 mg/kg/day, approximately 3x the C max and 0.4x the AUC at the MRHD....
Overdosage
10 OVERDOSAGE 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied CARDAMYST is supplied in cartons (NDC 83468-070-03) of 2 disposable nasal spray devices contained in a plastic carrying case. Each nasal spray device delivers two sprays containing a total of 70 mg etripamil. 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), with excursions permitted from 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). Do not test spray, prime or press the plunger before use. Discard the CARDAMYST device after use. 16.1 How Supplied CARDAMYST is supplied in cartons (NDC 83468-070-03) of 2 disposable nasal spray devices contained in a plastic carrying case. Each nasal spray device delivers two sprays containing a total of 70 mg etripamil.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.