Dehydrated Alcohol (ethyl alcohol)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

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

*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 that should be used in a single procedure is 5 mL..

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Ethyl Alcohol/Disulfiram Derivatives

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Disulfiram alters the intermediary metabolism of alcohol. Acetaldehyde is produced as a result of an initial metabolism of alcohol in the liver. Acetaldehyde is normally further oxidized by aldehyde dehydrogenase. However, this step is slowed by disulfiram and results in elevated acetaldehyde levels in the blood, which produces the undesirable effects.(1-2)

CLINICAL EFFECTS: Patients taking preparations that contain alcohol or using topical preparations that contain alcohol while taking disulfiram or agents related to it may experience throbbing in the head and neck, palpitations, tachycardia, hypotension, sweating, nausea, and vomiting.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer recommends that disulfiram never be administered to a patient who is in a state of alcohol intoxication. Patients should be advised that even small amounts of alcohol may trigger the reaction. U.S. manufacturer states that taking any alcohol containing products during the course of therapy with disulfiram or its derivatives is contraindicated.(2) Patients should be informed about unsuspected sources of alcohol such as elixirs and topical preparations.(2) Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (13): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: Disulfiram is used therapeutically in the treatment of alcoholism. The quantity of alcohol required to elicit the interaction varies with individuals.(2,4-5) Consumption of even small doses (e.g., 15 ml may lead to this interaction; therefore, concomitant administration should be avoided. Patients have suffered from this interaction from ingest-ing cough mixtures(6) and using topical preparations such as aftershave lotions(7) and antipsoriatic preparations(8) that contained alcohol. The duration of this interaction varies from 30 to 60 minutes to several hours, depending on the amount of alcohol consumed.(2,9) An overdose of disulfiram and alcohol may have caused a case of severe polyneuritis in one report,(10) and another report attributes the death of a patient to this interaction.(11) This interaction has also been reported in patients who came in contact with other organic solvents (e.g., paint, "mineral spirits") through inhalation; therefore, patients should be advised of this potential hazard as well.(12)

Ethyl Alcohol/Nifurtimox

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Nifurtimox may increase the risk of the disulfiram-like reaction. In vitro studies of similar agents including other nitrofurans and nitroheterocyclic compounds demonstrated inhibition of aldehyde dehydrogenase and other alcohol-oxidizing enzymes.(1) This results in the accumulation of acetaldehyde, which is responsible for the disulfiram-like reaction.

CLINICAL EFFECTS: Concurrent use of nifurtimox with alcohol may contribute to a disulfiram-type reaction resulting in symptoms of hypotension, tachycardia, nausea, sweating, facial flushing, headache, and vomiting.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised that concurrent use of nifurtimox and alcohol is contraindicated. Caution patients of the possible effects that may result from ingestion or application of products that contain alcohol while taking nifurtimox.(1) Patients should be informed about unsuspected sources of alcohol such as elixirs and topical preparations. Caution is also warranted when using intravenous preparations containing alcohol solvents in patients receiving nifurtimox. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (2): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: Clinical studies have not been conducted. Concomitant use of nifurtimox with alcohol may increase the incidence and severity of undesirable effects similar to other nitrofurans and nitroheterocyclic compounds.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Ethyl Alcohol/Selected Cephalosporins

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Certain cephalosporins have a methyltetrazolethiol side chain that resembles part of the disulfiram molecule. It has been suggested that the cephalosporins with this side chain interfere with the activity of the alcohol-metabolizing enzyme, aldehyde dehydrogenase, resulting in elevated concentrations of acetaldehyde and a "disulfiram-like" reaction.(1)

CLINICAL EFFECTS: A disulfiram-like reaction may occur in patients who ingest alcohol during and after taking some cephalosporins. Symptoms include throbbing in the head and neck, palpitations, tachycardia, hypotension, sweating, nausea, and vomiting.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving cephalosporins with a methyltetrazolethiol side chain should be cautioned about consuming alcohol during and for several days after therapy. Patients should be informed about unsuspected sources of alcohol such as elixirs and topical preparations. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (17) : Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: A disulfiram-like reaction has been reported following the ingestion of alcohol by patients receiving cefamandole,(2-4) cefoperazone, (5-7) cefotetan,(8) and moxalactam.(9-11) The reaction has been reported in patients who had been receiving the antibiotic periodically or continuously before alcohol consumption. The reaction occurred within 30 minutes of alcohol consumption.(5-7) In one patient, the reaction occurred after an injection of 15 ml of a 67% alcohol into the paraaortic space for celiac plexus alcohol block.(11) Cefonicid and ceforanide have exhibited these effects in animal studies. (12) However, another study showed that cefonicid did not interact with alcohol.(13) No interaction was found with cefazolin, cefotaxime, cefoxitin, cephalothin, or cephradine in animal studies.(14-15) A study in humans found no interaction with ceftizoxime.(1) These cephalosporins do not have a methyltetrazolethiol side chain. A single case reported a disulfiram-like reaction in a patient taking cefonicid therapy on two separate occasions.(16)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Ethyl Alcohol/Levoketoconazole; Ketoconazole

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism of action of this reaction is unknown. Like metronidazole, ketoconazole contains a methylated imidazole ring. Due to their structural similarity, it has been suggested that alcohol dehydrogenase inhibition like that caused by metronidazole may occur.(1) Levoketoconazole is an enantiomer of ketoconazole.(2)

CLINICAL EFFECTS: Concurrent use of ketoconazole with alcohol has been associated with a disulfiram-like reaction resulting in symptoms of flushing, rash, peripheral edema, nausea, and headache. Symptoms generally resolve within a few hours.(2,3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving levoketoconazole or ketoconazole should be instructed to use caution if drinking alcohol and to avoid excessive alcohol while taking levoketoconazole or ketoconazole.(2,3) Patients should be advised of the possible affects that may result from ingestion or application of products that contain alcohol while taking levoketoconazole or ketoconazole. Caution is also warranted when using intravenous preparations containing alcohol solvents in patients receiving levoketoconazole or ketoconazole. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (4): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: Ketoconazole has been associated with disulfiram-like reactions in patients who used alcohol. An 82-year old male with a history of alcohol abuse received a 1-week course of ketoconazole for esophageal candidiasis and had symptoms of nausea, vomiting and facial flushing. These symptoms were assumed to be due to alcohol ingestion.(1)

*None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

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

Less Frequent

• Ventricular fibrillation
• Ventricular tachycardia

Rare or Very Rare

• Heart block
• Heart failure

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and effectiveness in pediatric patients have not been established.

The concentrations of alcohol in blood after PTSMA were not measured, but dehydrated alcohol 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.

Dehydrated alcohol 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.

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

Dehydrated alcohol 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.

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.