Dehydrated Alcohol (ethyl alcohol)

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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)

Sedative Hypnotics; Alcohol/Sodium Oxybate

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: Oxybate may be associated with respiratory depression. As oxybate is taken at bedtime, concurrent use with alcohol or hypnotics may increase the risk for respiratory depression or loss of consciousness.(1-3) Primidone is metabolized to phenobarbital.

CLINICAL EFFECTS: Concurrent use of sodium oxybate and sedative hypnotics or alcohol may further increase the risk for respiratory depression and profound sedation or coma.(1,2) Fatalities have been reported.(3)

PREDISPOSING FACTORS: Based upon FDA evaluation of deaths in patients taking sodium oxybate, risk factors may include: use of multiple drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Note that in oxybate clinical trials for narcolepsy 78% - 85% of patients were also receiving concomitant CNS stimulants.(1-3)

PATIENT MANAGEMENT: The FDA states that sodium oxybate is contraindicated in patients also taking hypnotics or alcohol.(1,2) Significant quantities of alcohol may be present in medicinal products. Alcohol is 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: The FDA evaluated sodium oxybate postmarket fatal adverse event reports from the FDA Adverse Event Reporting System(AERS)and from the manufacturer. Although report documentation was not always optimal or complete, useful information was obtained. Factors which may have contributed to fatal outcome: concomitant use of one or more drugs which depress the CNS, more rapid than recommended upward dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Many deaths occurred in patients with serious psychiatric disorders such as depression and substance abuse. Other concomitant diseases may have also contributed to respiratory and CNS depressant effects of oxybate.(3)

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

Alcohol/Flibanserin

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

MECHANISM OF ACTION: Flibanserin may be associated with hypotension or syncopal episodes.(1)

CLINICAL EFFECTS: Concurrent use of alcohol in patients taking flibanserin may substantially increase the risk for hypotension or syncope.(1)

PREDISPOSING FACTORS: Patients with any degree of hepatic impairment, who are CYP2C19 poor metabolizers, or who also receive concomitant therapy with moderate or strong CYP3A4 inhibitors are expected to have increased systemic concentrations of flibanserin, adding to the risk for hypotension or syncopal episodes.(1) Hypotensive or syncopal episodes are more common when flibanserin is taken during waking hours.(1)

PATIENT MANAGEMENT: To decrease the risk for hypotension or syncope, counsel patients to take flibanserin at bedtime. Advise patients to wait at least two hours after consuming one or two standard alcoholic drinks before taking flibanserin at bedtime. If three or more standard alcoholic drinks are consumed, skip the dose of flibanserin that evening. After taking flibanserin at bedtime, patients should not use alcohol until the following day.(1) One standard alcoholic drink contains 14 grams of pure alcohol and is equivalent to one 12-ounce regular beer (5% alcohol), 5-ounces wine (12% alcohol), or 1.5 ounces of distilled spirits/shot (40% alcohol). Advise patients to lie down and call for medical help for persistent pre-syncope or lightheadedness.(1) Significant quantities of alcohol may be present in medicinal products. Alcohol is 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: A dedicated alcohol interaction study included 23 men and 2 women. Subjects took flibanserin or alcohol alone, or flibanserin and either 0.4 gram/kg or 0.8 gram/kg of alcohol. The alcohol dose was consumed over 10 minutes.(1) Co-administration of flibanserin and 0.4 gram/kg alcohol (approximately equal to 2 glasses of wine or 2 cans of beer) led to hypotension or syncope requiring therapeutic intervention in 4 of 23 subjects (17%). The magnitude of systolic blood pressure reductions ranged from 28 to 54 mmHg and diastolic blood pressure reductions ranged from 24 to 46 mmHg. In the flibanserin and alcohol 0.8 gram/kg group, 6 of the 24 subjects experienced orthostatic hypotension when moving from a sitting to standing position. The magnitude of systolic blood pressure reduction ranged from 22 to 48 mmHg and diastolic reductions ranged from 0 to 27 mmHg. One of the subjects required therapeutic intervention. In contrast, there were no events requiring therapeutic intervention when flibanserin or alcohol were administered alone.(1) In a study, 96 pre-menopausal women were given flibanserin or alcohol alone, or flibanserin with 0.2 gram/kg, 0.4 gram/kg, or 0.6 gram/kg alcohol in the morning. Although no subjects had syncope or hypotension requiring therapeutic intervention, subjects were not allowed to stand for orthostatics if they were hypotensive (blood pressure <90/60 mmHg) or dizzy while semi-recumbent. More subjects who received the combination of flibanserin and alcohol than those who received flibanserin or alcohol alone had missing or delayed orthostatic measurements due to hypotension or dizziness.(1) A study of 64 pre-menopausal women who drank 0.4 g/kg of alcohol two, four, or six hours before taking a dose of flibanserin 100 mg or placebo found that there was no difference in the incidence of orthostatic hypotension or hypotension at all time points between subjects who received alcohol alone, flibanserin alone, or both.(1) A study of 24 pre-menopausal women compared flibanserin or alcohol alone, or flibanserin given 2.5 hours or 4 hours after consumption of 0.4 gram/kg alcohol. There were no cases of syncope, dizziness, or somnolence in any group.(1)

Alcohol/Furazolidone

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

MECHANISM OF ACTION: In vitro studies show that furazolidone produces an inhibition of aldehyde dehydrogenase.(2,3) This results in the accumulation of acetaldehyde, which is responsible for the disulfiram-like reaction.

CLINICAL EFFECTS: Concurrent use of furazolidone with alcohol has been associated with a disulfiram-type reaction resulting in symptoms of hypotension, tachycardia, nausea, sweating, facial flushing, headache, and vomiting.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of furazolidone states that alcohol is not recommended during and for at least 4 days after taking furazolidone.(1) Patients should be advised of the possible effects that may result from ingestion or application of products that contain alcohol while taking furazolidone. 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 (22): 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: In vitro studies have found that furazolidone inhibits aldehyde dehydrogenase (ALDH).(2,3) In one study, furazolidone nanoemulsion inhibited 99.75% of ALDH activity while free furazolidone inhibited 25% of ALDH activity.(3)

Ethyl Alcohol/Acitretin

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

MECHANISM OF ACTION: Ethanol trans esterifies acitretin into etretinate,(1-3) which is stored in adipose tissue and slowly eliminated.(1)

CLINICAL EFFECTS: Ingestion of ethanol, even sporadically, during acitretin usage and for 2 months after discontinuation of acitretin may result in formation of etretinate. Etretinate is also highly teratogenic and is slowly eliminated from the body over several years after discontinuation.(4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of acitretin states that use of ethanol during or for 2 months after acitretin therapy in females is contraindicated.(4) Females on acitretin therapy should be counseled to avoid consumption and use of ethanol containing products during and for two months after acitretin use.(4) 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 (6): 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: In a 2-way cross-over study in 10 subjects, consumption of a single dose of acitretin (100 mg) during ethanol ingestion (1.4 g/kg) resulted in formation of etretinate in all 10 subjects. The levels of etretinate formed were comparable to a 5 mg dose of etretinate. There was no detectable etretinate levels in any subject during administration of acitretin without ethanol.(4) In a study in 10 subjects treated with acitretin (30 mg daily for 3 months), 7 patients had detectable etretinate levels, 4 of which were teratogenic. Consumption of ethanol was linked to the formation of etretinate.(1) In a study in 86 patients treated with acitretin, 30 patients had detectable levels of etretinate. No etretinate was found in 20 subjects who reported no ethanol intake. Etretinate was found in all 16 subjects with an average weekly alcohol consumption of greater than 200 g (approximately 15 servings/week). Etretinate was found in 15 of 50 patients with an average weekly ethanol intake less than 200 g.(5) The half-life of etretinate has been estimated at 120 days (range 84-168 days). In a study of 47 patients treated with etretinate, 5 had detectable etretinate levels 2.1 years to 2.9 years after discontinuation of therapy. However, one patient who reported sporadic ethanol intake had detectable etretinate levels 52 months after discontinuation of acitretin.(4)

Ethyl Alcohol/Benzodiazepines

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

MECHANISM OF ACTION: Concurrent use may result in additive central nervous system depressant effects. Concurrent use may also result in altered absorption, altered distribution, or decreased elimination leading to higher concentrations of the benzodiazepine in the brain.(1-4)

CLINICAL EFFECTS: Concurrent use of benzodiazepines and alcohol-containing products may result in enhanced disruption of psychomotor performance and increased central nervous system depression. Increased CNS depression may result in profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be informed that alcohol consumption may result in significant decreased psychomotor performance and its associated risks. Use of a short acting benzodiazepine may minimize the potential for extreme effects. If suicide or drug abuse is a concern, benzodiazepine use may be ill advised, since alcohol tends to greatly increase benzodiazepine-induced CNS depression in acute overdosage. Patients should be informed about unsuspected sources of alcohol such as medications. 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 (18): 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: Several articles have detailed enhanced disruption of psychomotor performance and increased CNS depression with concurrent use of diazepam and alcohol.(1-6) Evidence shows that temazepam and the other short-acting or intermediate-acting benzodiazepines (e.g., alprazolam, halazepam, triazolam) tend to result in less profound alcohol interactions.(7) Although one study showed no effect on triazolam pharmacokinetics, a clinically significant pharmacodynamic interaction cannot be ruled out.(8) Other reports have shown clinically significant effects from concurrent triazolam and alcohol use.(9,10) In 8 healthy subjects, concurrent midazolam and alcohol resulted in impairment of immediate recall.(11) In a similar study, the hypnotic effect of midazolam was augmented by alcohol.(12) In a study involving 9 subjects, measurements of total reaction time were longer after concurrent alcohol and lorazepam as compared to the use of either agent alone.(13) Reports have been conflicting regarding the actions of chlordiazepoxide when combined with alcohol. Differences in time of exposure, dosage, and response parameters have been used to explain the inconsistent findings with chlordiazepoxide.(14)

Ethyl Alcohol/Fexinidazole;Metronidazole;Tinidazole

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

MECHANISM OF ACTION: In vitro studies show that metronidazole produces an inhibition of aldehyde dehydrogenase and other alcohol-oxidizing enzymes.(1-5) This results in the accumulation of acetaldehyde, which is responsible for the disulfiram-like reaction. A similar process may occur with fexinidazole(6) and tinidazole.(7)

CLINICAL EFFECTS: Concurrent use of oral metronidazole with alcohol has been associated with a disulfiram-type reaction resulting in symptoms of hypotension, tachycardia, nausea, sweating, facial flushing, headache, and vomiting.(7-10) It has been suggested that some patients find this combination of agents a pleasant experience, citing giddiness and excitement as rationale for abuse.(11)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving fexinidazole should be instructed to avoid alcohol during and for at least 48 hours after taking fexinidazole.(6) Patients should be advised of the possible affects that may result from ingestion or application of products that contain alcohol while taking metronidazole. Patients receiving tinidazole should be instructed to avoid alcohol during and for 3 days after taking tinidazole.(7) 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 metronidazole or tinidazole. 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 (22): 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: In a case report,(13) a patient developed disulfiram-like reactions after receiving concurrent metronidazole and intravenous sulfamethoxazole-trimethoprim, which is solubilized in a 10% alcohol base. In another case report, a female patient using vaginal inserts containing metronidazole once daily at bedtime ingested two or three drinks containing 30ml of vodka on the fifth day of metronidazole therapy.(14) About a half hour later, the patient inserted the metronidazole vaginal tablet and awoke one hour later with a severe burning sensation in her stomach, a severe headache, and nausea accompanied by a cold sweat. These symptoms resolved in about four hours. Other studies have failed to observe a disulfiram-like reaction between alcohol and metronidazole.(15-21)

Ethyl Alcohol/Fomepizole

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

MECHANISM OF ACTION: Fomepizole inhibits the activity of alcohol dehydrogenase, an enzyme needed to help eliminate alcohol. Additionally, alcohol can decrease the rate of elimination of fomepizole by the same mechanism.

CLINICAL EFFECTS: This interaction may cause an increase in the adverse events associated with both increased alcohol levels as well as increased fomepizole levels. Increase fomepizole levels may result in headache, nausea, dizziness, and drowsiness. Increased alcohol levels may cause sedation, decreased motor skills, and loss of consciousness.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised of this potential hazard and should be encouraged not to ingest alcohol containing products during the course of therapy with fomepizole. Patients should be informed about unsuspected sources of alcohol, such as medications. 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: Fomepizole (10-20 mg/kg) significantly reduced the rate of elimination of ethanol by approximately 40%, given in moderate doses to healthy volunteers. This occurred because of inhibition of alcohol dehydrogenase. Similarly, ethanol decreased the rate of elimination of fomepizole by approximately 50%, by the same mechanism.(1)

Ethyl Alcohol/Levamisole

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

MECHANISM OF ACTION: The exact mechanism of this interaction is unknown.

CLINICAL EFFECTS: Levamisole hydrochloride has been reported to produce disulfiram-like side effects following the ingestion of alcohol. Some signs of this interaction include throbbing in the head and neck, flushing, palpitations, tachycardia, hypotension, sweating, nausea, and vomiting.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised of the possible affects that may result from the concurrent use of levamisole and alcohol or alcohol containing products. Patients should be informed about unsuspected sources of alcohol such as medications. 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: The duration of this interaction may vary depending on the amount of alcohol consumed. The quantity of alcohol needed to elicit this interaction varies with individuals.

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.

Alcohol/Apomorphine

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

MECHANISM OF ACTION: Apomorphine is associated with hypotension or syncopal episodes. High doses of alcohol (0.6 gram/kg) may increase the levels of apomorphine.(1)

CLINICAL EFFECTS: Concurrent use of alcohol in patients taking apomorphine may substantially increase the risk for hypotension or syncope.(1)

PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in renal and hepatic impairment.

PATIENT MANAGEMENT: Counsel patients to avoid alcohol while using apomorphine due to the increased risk of hypotension.(1) Significant quantities of alcohol may be present in medicinal products. Alcohol is 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 (3): 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: Healthy volunteers who had high dose ethanol (0.6 gram/kg, or 3 standardized alcoholic beverages) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.1 mm Hg and in supine diastolic blood pressure (DBP) of 10.5 mm Hg, and a mean largest decrease in standing SBP and DBP of 11.3 mm Hg and 12.6 mm Hg, respectively. The maximum decrease in SBP and DBP was 61 mm Hg and 51 mm Hg, respectively. With low dose ethanol (0.3 gram/kg), a mean largest decrease in supine SBP and DBP of 10.2 mm Hg and 9.9 mm Hg, respectively, and in standing SBP and DBP of 8.4 mm Hg and 7.1 mm Hg were seen. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively. High dose ethanol increased the maximum concentration (Cmax) of apomorphine by 63 %. Low dose ethanol did not significantly affect the pharmacokinetics of apomorphine. However, an increase in the hypotensive effect of apomorphine was still noted, as described above.(1)

Alcohol; Propylene Glycol/Secnidazole

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

MECHANISM OF ACTION: Alcohol and propylene glycol may potentiate the adverse effects of secnidazole.(1)

CLINICAL EFFECTS: Concurrent use of alcohol or preparations containing ethanol or propylene glycol in patients taking secnidazole may increase the risk of side effects, including nausea, vomiting, diarrhea, abdominal pain, headache and dizziness.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Counsel patients to avoid alcohol and preparations containing ethanol or propylene glycol until at least 2 days after completing therapy with secnidazole.(1) Significant quantities of alcohol may be present in medicinal products. Alcohol is 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 (3): 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: In vitro studies showed that secnidazole had no effect on aldehyde dehydrogenase activity. However, postmarketing observations of adverse reactions of nausea, vomiting, diarrhea, abdominal pain, dizziness, and headache with concomitant use of secnidazole and alcohol have been reported.(1)

Ethyl Alcohol/Chloral Hydrate Derivatives

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

MECHANISM OF ACTION: Alcohol stimulates the reduction of chloral hydrate to trichloroethanol, which is longer-acting than the parent compound.(1) Trichloroethanol in turn inhibits the oxidation of alcohol to acetaldehyde by alcohol dehydrogenase. Enhanced CNS depression occurs. The mechanism for the development of vasodilation is not known but is not related to increased acetaldehyde levels.(1,2,4)

CLINICAL EFFECTS: Concurrent ingestion of chloral hydrate and alcohol results in greater CNS depression than that occurring when either agent is taken alone.(2,3) In addition, a disulfiram-like reaction characterized by vasodilation, flushing, tachycardia, hypotension, or headache may occur when alcohol is ingested by a patient who has been receiving chloral hydrate for several days.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: All patients taking chloral hydrate should be warned that the CNS depressant effects of both chloral hydrate and alcohol are increased by concurrent ingestion and the possibility of a disulfiram-like reaction. Patients should be informed about unsuspected sources of alcohol such as medications. 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 (5): 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: Patients with cardiovascular disease who receive chloral hydrate long-term should be especially careful about ingesting alcohol in view of the tachycardia and hypotension that can result from the vasodilation reaction.

Ethyl Alcohol/Glinides; Sulfonylureas

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

MECHANISM OF ACTION: Alcohol can induce hypoglycemia and interfere with gluconeogenesis in the liver by means of intrinsic hypoglycemic activity.(1-3) Some alcoholic beverages may increase serum glucose levels from their high carbohydrate content.(4) Chronic alcohol intake may decrease half-life of sulfonylureas by increasing liver metabolism.(1, 5-8)

CLINICAL EFFECTS: Alcohol consumption while on a glinide or sulfonylureas may result in a range of reactions, from mild flushing to severe hypoglycemic reactions. Alcohol consumption during chlorpropamide therapy has resulted in a disulfiram-like reaction.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Diabetics should be cautioned about the effects of alcohol consumption on diabetic control, possible flushing with concurrent use, and about unsuspected sources of alcohol such as medications. Patients on chlorpropamide therapy should be counseled about the possibility of a disulfiram-like reaction to alcohol consumption. 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 (21): 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: Chlorpropamide has been reported to induce facial flushing (5,9-18) and a disulfiram-like reaction(4,9,10,18,19) following alcohol consumption. Tolbutamide has been shown to interact with alcohol in nonalcoholic diabetic patients, alcoholics, and normal subjects.(2,3,6-8,16,17) There is one report of reduced tolerance for alcohol in a patient on tolazamide therapy.(20) In a study in 10 normal subjects, administration of ethanol with glipizide resulted in a delay in return to fasting glucose levels. The time of onset and the extent of hypoglycemia were not altered.(21) Glipizide and glyburide have been reported to have a very low incidence of disulfiram-like reactions with concurrent alcohol; however, in one study, 5 of 11 patients taking glyburide developed flushing after a test dose of alcohol.(18)

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)

Ethyl Alcohol/Varenicline

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

MECHANISM OF ACTION: The mechanism of this interaction has not been described.

CLINICAL EFFECTS: Concurrent use of varenicline and alcohol-containing products may result in increased intoxicating effects of alcohol, aggressive behavior and/or amnesia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised that varenicline can change the way they react to alcohol. Case reports have described decreased alcohol tolerance, sometimes associated with aggressive behavior and/or amnesia with alcohol consumption which was previously tolerated. Patients and providers should be aware of unsuspected sources of alcohol such as medications. Reduce the use of non-essential alcohol containing drugs (e.g. cough and cold products) when possible. 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 - For comparison, the US National Institute on Alcohol Abuse and Alcoholism definition of a Standard Drink (e.g. 12oz of 5% beer, 5oz of 12% wine) contains 14 grams of alcohol.

DISCUSSION: A search of the FDA Adverse Event Reporting System (FAERS) identified 48 cases of adverse events due to the combination of varenicline and alcohol.(1) Aggressive behavior was described in 37 cases. In these cases, the amount of alcohol consumed was insufficient to explain the event. More than half of the patients involved described their behavior as a significant change from their behavior prior to varenicline treatment. In 16 of the 37 cases, patients reported no or impaired memory of the event; most of these cases were also associated with physical harm to a person and/or property. Decreased alcohol tolerance was observed in 11 cases in patients who consumed quantities of alcohol which previously did not cause adverse effects. Outcomes included an automobile accident leading to arrest and a significant facial injury. Most of the patients in these cases described poor memory of their experience.

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• Diabetic coma
• Seizure disorder
• Urinary tract infection

• Alcohol use disorder
• Diabetes mellitus
• Disease of liver
• Invasive procedure on brain
• Porphyria
• Postpartum hemorrhage
• Pregnancy
• Severe renal impairment
• Shock

• Hypotension

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There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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