Dehydrated Alcohol

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 dehydrated alcohol injection that should be used in a single procedure is 5 mL.

Dehydrated alcohol injection 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. Dehydrated alcohol injection should appear as a clear, colorless solution.

Discard unused portion.

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.

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

Dehydrated alcohol injection 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.

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.

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.

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 dehydrated alcohol injection 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.

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 dehydrated alcohol injection 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.

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.

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.