These Highlights Do Not Include All The Information Needed To Use Ablysinol ®

Ampules:                            

Manufactured for:

BPI Labs, LLC, Largo, FL 33773 USA

Manufactured by:

Sintetica SA

Via Penate 5

6850 Mendrisio, Switzerland

Vials:

Manufactured by:

BPI Labs, LLC

12393 Belcher Rd S, Suite 450

Largo, FL 33773

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.

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.

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.

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 C₂H₆O 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:

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, 3^rd degree atrio-ventricular block occurring during the procedure, and no clinical recovery between 12-48 hours after the procedure.

Safety and effectiveness in pediatric patients have not been established.

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.

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.

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.

None.

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.

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.

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.

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.

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.

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.

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.

• 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)

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

• 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)

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

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

• 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

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-144-01

5 mL - VIAL - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-144-10

5 mL - VIAL - CARTON - 10 PACK

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

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.

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-01

1 mL - AMPULE - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-10

1 mL - AMPULE - CARTON - 10 PACK

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-02

5mL - AMPULE - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-15

5mL - AMPULE - CARTON - 10 PACK

The median lethal dose (LD₅₀) 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 LD₅₀ for ethyl alcohol given by subcutaneous injection is 8285 mg/kg in mice.

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.

Ampules:                            

Manufactured for:

BPI Labs, LLC, Largo, FL 33773 USA

Manufactured by:

Sintetica SA

Via Penate 5

6850 Mendrisio, Switzerland

Vials:

Manufactured by:

BPI Labs, LLC

12393 Belcher Rd S, Suite 450

Largo, FL 33773

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.

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.

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.

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 C₂H₆O 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:

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, 3^rd degree atrio-ventricular block occurring during the procedure, and no clinical recovery between 12-48 hours after the procedure.

Safety and effectiveness in pediatric patients have not been established.

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.

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.

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.

None.

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.

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.

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.

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.

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.

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.

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.

• 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)

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

• 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)

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

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

• 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

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-144-01

5 mL - VIAL - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-144-10

5 mL - VIAL - CARTON - 10 PACK

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

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.

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-01

1 mL - AMPULE - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-10

1 mL - AMPULE - CARTON - 10 PACK

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-02

5mL - AMPULE - LABEL

ABLYSINOL® (Dehydrated Alcohol Injection, USP)

NDC 54288-105-15

5mL - AMPULE - CARTON - 10 PACK

The median lethal dose (LD₅₀) 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 LD₅₀ for ethyl alcohol given by subcutaneous injection is 8285 mg/kg in mice.

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.