Label: DEHYDRATED ALCOHOL- alcohol injection, solution

  • NDC Code(s): 54288-105-01, 54288-105-02, 54288-105-10, 54288-105-15
  • Packager: BPI Labs, LLC
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: New Drug Application

Drug Label Information

Updated December 30, 2020

If you are a consumer or patient please visit this version.

  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use ABLYSINOL ® safely and effectively. See full prescribing information for ABLYSINOL.

    ABLYSINOL (dehydrated alcohol) injection, for cardiac septal branch intra-arterial use

    Initial U.S. Approval: 1946

    INDICATIONS AND USAGE

    ABLYSINOL is an ablative agent indicated to induce controlled cardiac septal infarction to improve exercise capacity in adults with symptomatic hypertrophic obstructive cardiomyopathy who are not candidates for surgical myectomy. ( 1)

    DOSAGE AND ADMINISTRATION

    • Inject small volumes over 1 to 2 minutes percutaneously into septal arterial branches, using the minimal dose necessary to achieve the desired reduction in peak left ventricular outflow tract pressure gradient. ( 2.1)
    • In most situations, a dose of 1 mL to 2 mL is sufficient. The maximum dose that should be used in a single procedure is 5 mL. ( 2.1)

    DOSAGE FORMS AND STRENGTHS

    • Injection: 1 mL or 5 mL of ethyl alcohol ≥ 99% by volume as a clear, colorless liquid in a single-dose glass ampule. ( 3)

    CONTRAINDICATIONS

    • None ( 4)

    WARNINGS AND PRECAUTIONS

    • Transient heart block: Transient heart block is common at the time of injection. A temporary pacing wire is routinely inserted to mitigate transient heart block. (5.1)
    • Persistent heart block: Approximately 10% of complete heart block events become permanent and require placement of a permanent pacemaker. (5.1)
    • Remove the temporary pacemaker lead if no episode of high-degree atrioventricular block occurs. (5.1)
    • Monitor the patient for heart failure, chest pain, and arrhythmias several days after the procedure. (5.1, 5.2, 5.3)

    ADVERSE REACTIONS

    Adverse reactions include arrhythmias, including ventricular tachycardia and/or ventricular fibrillation. ( 6)

    To report SUSPECTED ADVERSE REACTIONS, contact Belcher Pharmaceuticals at (727) 471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    USE IN SPECIFIC POPULATIONS

    • ABLYSINOL is not recommended during pregnancy. Maternal use is not expected to result in fetal exposure to the drug. ( 8.1)
    • The rate of heart blocks and dysrhythmia increased with age. (8.5)

    See 17 for PATIENT COUNSELING INFORMATION

    Revised: 10/2018

  • Table of Contents
  • 1 INDICATIONS AND USAGE

    ABLYSINOL ® is indicated to induce controlled cardiac septal infarction to improve exercise capacity in adults with symptomatic hypertrophic obstructive cardiomyopathy who are not candidates for surgical myectomy.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Recommended Dosing

    Use the minimum dose necessary to achieve the desired reduction in peak left ventricular outflow tract pressure gradient. Inject small volumes over 1 to 2 minutes percutaneously into septal arterial branches, guided by assessment of the gradient. In most situations, a dose of 1 mL to 2 mL is sufficient. The maximum dose of ABLYSINOL that should be used in a single procedure is 5 mL.

    2.2 Administration

    ABLYSINOL should only be administered under the supervision of a qualified interventional cardiologist experienced in the percutaneous transluminal septal myocardial ablation procedure.

    Inspect visually for particulate matter and discoloration prior to administration. ABLYSINOL should appear as a clear, colorless solution.

  • 3 DOSAGE FORMS AND STRENGTHS

    Injection: 1 mL or 5 mL of ethyl alcohol ≥ 99% by volume as a clear, colorless liquid in a single-dose glass ampule.

  • 4 CONTRAINDICATIONS

    None.

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Heart Block

    Transient Heart Block
    Transient heart block is common at the time of dehydrated alcohol, such as ABLYSINOL, injection into a septal artery. Prior to the injection, a temporary pacing wire is routinely inserted into the apex of the right ventricle, usually via the femoral vein, to treat transient heart block. The pacing lead can be removed if no episode of high-degree atrioventricular block occurs, usually after several hours of observation following percutaneous transluminal septal myocardial ablation.

    Persistent Heart Block
    Approximately 10% of complete heart block events become permanent and require placement of a permanent pacemaker following percutaneous transluminal septal myocardial ablation. Risk factors for permanent pacemaker dependency after septal ablation include a baseline PQ interval > 160 ms, baseline minimum heart rate < 50 bpm, baseline left ventricular outflow gradient > 70 mmHg, maximum QRS during the first 48 hours > 155 ms, 3rd degree atrio-ventricular block occurring during the procedure, and no clinical recovery between 12-48 hours after the procedure.

    5.2 Myocardial Infarction

    Injection of dehydrated alcohol is intended to create a controlled myocardial infarction for therapeutic purposes. However, excessive myocardial necrosis and subsequent heart failure have been reported. Factors increasing the risk of excessive tissue necrosis include higher volume of alcohol used and a higher number of septal branches injected to reduce the left ventricular outflow tract gradient.

    5.3 Ventricular Arrhythmia

    Ventricular tachycardia and ventricular fibrillation requiring electrocardioversion occurred at a frequency of approximately 1%. Perform continuous electrocardiographic monitoring for 48 hours after the procedure.

  • 6 ADVERSE REACTIONS

    Heart block [ see Warnings and precautions (5.1)]

    The following other adverse reactions associated with percutaneous transluminal septal myocardial ablation with the use of dehydrated alcohol, such as ABLYSINOL, were identified in the literature: Ventricular tachycardia and ventricular fibrillation.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary
    The concentrations of alcohol in blood after PTSMA were not measured, but ABLYSINOL is not expected to increase significantly the systemic concentrations of endogenous alcohol following administration into a septal artery during percutaneous transluminal septal myocardial ablation. Maternal use is not expected to result in fetal exposure to the drug.

    Clinical Considerations
    ABLYSINOL for percutaneous transluminal septal myocardial ablation has not been evaluated in pregnant women and is not recommended during pregnancy. When possible, the percutaneous transluminal septal myocardial ablation procedure should be postponed in women until the postpartum period.

    Data
    Animal reproduction studies have shown an adverse effect on the fetus and chronic fetal alcohol exposure is known to cause developmental defects in human. The developmental effects of acute ethanol exposure, such as from percutaneous transluminal septal myocardial ablation, have not been studied in pregnant or lactating women.

    8.2 Lactation

    ABLYSINOL is not expected to increase significantly the systemic concentrations of endogenous alcohol following administration into a septal artery during percutaneous transluminal septal myocardial ablation and breastfeeding is not expected to result in exposure of the child to the drug.

    8.4 Pediatric Use

    Safety and effectiveness in pediatric patients have not been established.

    8.5 Geriatric Use

    A comparison of the outcomes in patients with hypertrophic obstructive cardiomyopathy in patients < 60 years old and in patients ≥ 60 years old showed similar improvement in exercise capacity after ablation. The rate of heart blocks and dysrhythmia increased with age. Permanent pacemaker dependency increased to 34% in patients > 60 years old.

  • 10 OVERDOSAGE

    There is a direct correlation between the volume of alcohol and size of iatrogenic myocardial infarction. Stop the procedure if there is failure to reduce the left ventricular outflow tract pressure gradient to less than 10 mmHg when reaching a total dose of 5 mL.

  • 11 DESCRIPTION

    ABLYSINOL (dehydrated alcohol) injection is a sterile, preservative free solution of ≥ 99% by volume ethyl alcohol and no excipients. ABLYSINOL is for cardiac septal branch intra-arterial use. It has a molecular formula of C 2H 6O and a molecular weight of 46.07.

    Dehydrated Alcohol Injection, USP is a potent tissue toxin. Ethanol is a clear, colorless, volatile, and flammable liquid miscible with water. It has the following structural formula:

    chemicalstructure

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Dehydrated alcohol is a tissue toxin that produces a myocardial infarction when injected through an intra-arterial catheter into a target septal vessel, which causes the hypertrophied septum to thin.

    12.2 Pharmacodynamics

    A dose independent, approximate 70% reduction of the peak pressure gradient across left ventricular outflow tract is observed after injection of alcohol volumes in the range of 1-4 mL. Remodeling contributes about 20% to the 70% total reduction in peak pressure gradient across the left ventricular outflow tract measured 12 months after septal ablation. Other markers, such as infarct size or peak concentration of creatine kinase-MB (CK-MB), in contrast to peak pressure gradient across the left ventricular outflow tract, vary in proportion to the injected alcohol volume in the 1-4 mL range.

    12.3 Pharmacokinetics

    Because injection of ABLYSINOL during septal ablation is not expected to increase the systemic concentrations of endogenous alcohol significantly, the pharmacokinetics of dehydrated alcohol are not expected to be clinically significant.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Ethanol (of alcohol beverages) was added to Group 1 International Agency for Research on Cancer (IARC) Carcinogenicity Ratings (IARC monographs). Substances in this group are either carcinogenic to humans, or there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the substance acts through a relevant mechanism of carcinogenicity. Alcohol consumption has been associated with various cancers, including liver, esophageal, breast, prostate, and colorectal cancer. Since ABLYSINOL is not expected to reach the systemic circulation following administration into a septal artery during percutaneous transluminal septal myocardial ablation, the recommended clinical use of the drug product is not expected to have carcinogenic risk in patients.

    Literature reports suggest that ethanol is not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or in vitro chromosomal aberration assays. Ethanol is metabolized to acetaldehyde, which is a known mutagen.

    There are no data from either animal or human studies regarding potential for the impairment of fertility.

    13.2 Animal Toxicology and/or Pharmacology

    The median lethal dose (LD 50) values for ethyl alcohol given by intravenous and oral routes are 1440 and 7060 mg/kg in rats and 1973 and 3450 mg/kg in mice, respectively. The LD 50 for ethyl alcohol given by subcutaneous injection is 8285 mg/kg in mice.

  • 14 CLINICAL STUDIES

    Evidence of the effectiveness of ethanol on exercise capacity in adults with symptomatic hypertrophic obstructive cardiomyopathy who are not candidates for surgical myectomy was obtained from literature involving over 4000 patients.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    ABLYSINOL (dehydrated alcohol) injection is a clear, colorless liquid supplied in clear, glass, single-dose ampules. Each mL contains ≥99% by volume ethyl alcohol.

    NDC
    VolumeSingle ampuleCarton of 10 ampules
     1 mL 54288-105-01 54288-105-10
     5 mL 54288-105-02 54288-105-15

    Store at room temperature, between 20°C and 25°C (68°F and 77°F). Do not refrigerate or freeze. Highly flammable, store away from any heat source.

  • SPL UNCLASSIFIED SECTION

    Manufactured for:

    BPIlogo

    BPI Labs, LLC, Largo, FL 33777 USA

    Manufactured by:
    Sintetica SA
    Via Penate 5
    6850 Mendrisio, Switzerland

  • PRINCIPAL DISPLAY PANEL - 1 mL 

    ABLYSINOL® (Dehydrated Alcohol Injection, USP)

    1 mL

    NDC 54288-105-01

    For Cardiac Septal Branch Intra-Arterial Use.

    Usual Dose: see prescribing information.

    Store away from any heat source.

    Each mL contains:
    ≥ 99% by volume ethyl alcohol
    (a sterile, preservative free solution)

    WARNING: Do not use if discolored or precipitated.

    10 Single Dose Ampules x 1 mL

    HIGHLY FLAMMABLE

    Rx Only

    LOT

    EXP

    Rev.R-1806

    ablysinol1mL

  • PRINCIPAL DISPLAY PANEL - 5 mL 

    ABLYSINOL® (Dehydrated Alcohol Injection, USP)

    5 mL

    NDC 54288-105-02

    For Cardiac Septal Branch Intra-Arterial Use.

    Usual Dose: see prescribing information.

    Store away from any heat source.

    Each mL contains:
    ≥ 99% by volume ethyl alcohol
    (a sterile, preservative free solution)

    WARNING: Do not use if discolored or precipitated.

    10 Single Dose Ampules x 5 mL

    HIGHLY FLAMMABLE

    Rx Only

    LOT

    EXP

    Rev. R-1806

    ablysinol5mL

  • PRINCIPAL DISPLAY PANEL - 5 mL Carton

    ABLYSINOL® (Dehydrated Alcohol Injection, USP)

    5 mL

    NDC 54288-105-15

    For Cardiac Septal Branch Intra-Arterial Use.

    Usual Dose: see prescribing information.

    Store away from any heat source.

    Each mL contains:
    ≥ 99% by volume ethyl alcohol
    (a sterile, preservative free solution)

    WARNING: Do not use if discolored or precipitated.

    10 Single Dose Ampules x 5 mL

    HIGHLY FLAMMABLE

    Rx Only

    LOT

    EXP

    Rev. R-1806

    ablysinol5mlcover

  • INGREDIENTS AND APPEARANCE
    DEHYDRATED ALCOHOL 
    alcohol injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:54288-105
    Route of AdministrationPERCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ALCOHOL (UNII: 3K9958V90M) (ALCOHOL - UNII:3K9958V90M) ALCOHOL1 mL  in 1 mL
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:54288-105-1010 in 1 CARTON10/24/2018
    1NDC:54288-105-011 mL in 1 AMPULE; Type 0: Not a Combination Product
    2NDC:54288-105-1510 in 1 CARTON10/24/2018
    2NDC:54288-105-025 mL in 1 AMPULE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA20798710/24/2018
    Labeler - BPI Labs, LLC (078627620)
    Establishment
    NameAddressID/FEIBusiness Operations
    Sintetica SA480895478manufacture(54288-105) , analysis(54288-105) , label(54288-105) , pack(54288-105)
    Establishment
    NameAddressID/FEIBusiness Operations
    Sintetica-Bioren SA483148768analysis(54288-105)
    Establishment
    NameAddressID/FEIBusiness Operations
    Sigma-Aldrich Ireland Ltd989299516api manufacture(54288-105) , analysis(54288-105) , label(54288-105) , pack(54288-105)