Disulfiram

Disulfiram is an alcohol antagonist drug.

Chemical Name: bis(diethylthiocarbamoyl) disulfide.

Structural Formula:

C10H20N2S4     M.W. 296.54

Disulfiram occurs as a white to off-white, odorless, and almost tasteless powder, soluble in water to the extent of about 20 mg in 100 mL, and in alcohol to the extent of about 3.8 g in 100 mL.

Each tablet for oral administration contains 250 mg or 500 mg disulfiram, USP. Tablets also contain colloidal silicon dioxide, anhydrous lactose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and stearic acid.

(See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS.)

OPTIC NEURITIS, PERIPHERAL NEURITIS, POLYNEURITIS, AND PERIPHERAL NEUROPATHY MAY OCCUR FOLLOWING ADMINISTRATION OF DISULFIRAM.

Multiple cases of hepatitis, including both cholestatic and fulminant hepatitis, as well as hepatic failure resulting in transplantation or death, have been reported with administration of disulfiram.

Occasional skin eruptions are, as a rule, readily controlled by concomitant administration of an antihistaminic drug.

In a small number of patients, a transient mild drowsiness, fatigability, impotence, headache, acneform eruptions, allergic dermatitis, or a metallic or garlic-like aftertaste may be experienced during the first two weeks of therapy. These complaints usually disappear spontaneously with the continuation of therapy, or with reduced dosage.

Psychotic reactions have been noted, attributable in most cases to high dosage, combined toxicity (with metronidazole or isoniazid), or to the unmasking of underlying psychoses in patients stressed by the withdrawal of alcohol.

Disulfiram should never be administered to a patient when he is in a state of alcohol intoxication, or without his full knowledge.

The physician should instruct relatives accordingly.

The patient must be fully informed of the disulfiram-alcohol reaction. He must be strongly cautioned against surreptitious drinking while taking the drug, and he must be fully aware of the possible consequences. He should be warned to avoid alcohol in disguised forms, i.e., in sauces, vinegars, cough mixtures, and even in aftershave lotions and back rubs. He should also be warned that reactions may occur with alcohol up to 14 days after ingesting disulfiram.

The Disulfiram-Alcohol Reaction

Disulfiram plus alcohol, even small amounts, produce flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.

The intensity of the reaction varies with each individual, but is generally proportional to the amounts of disulfiram and alcohol ingested. Mild reactions may occur in the sensitive individual when the blood alcohol concentration is increased to as little as 5 to 10 mg per 100 mL. Symptoms are fully developed at 50 mg per 100 mL, and unconsciousness usually results when the blood alcohol level reaches 125 to 150 mg.

The duration of the reaction varies from 30 to 60 minutes, to several hours in the more severe cases, or as long as there is alcohol in the blood.

Concomitant Conditions

Because of the possibility of an accidental disulfiram-alcohol reaction, disulfiram should be used with extreme caution in patients with any of the following conditions: diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic and acute nephritis, hepatic cirrhosis or insufficiency.

Serious side effects have been reported with disulfiram including the following:

• Liver toxicity. Tell your healthcare provider right away if you have some or all of the following symptoms of liver toxicity:
  • excessive fatigue or weakness
  • loss of appetite
  • nausea
  • vomiting
  • yellowing of the skin or eyes
  • dark urine

Disulfiram can also cause blurred vision and drowsiness. Do not drive or operate heavy machinery until you know how disulfiram affects you.

Do not take disulfiram if you:

• are allergic to disulfiram or to any of its ingredients
• are allergic to thiuram derivatives used in pesticides and rubber vulcanization
• have recently taken metronidazole, paraldehyde, alcohol, or alcohol-containing preparations such as cough syrups and tonics
• have severe myocardial disease or coronary occlusion
• have psychoses

• Alcoholism
• Liver Disease

Disulfiram blocks an enzyme that is involved in metabolizing alcohol intake. Disulfiram produces very unpleasant side effects when combined with alcohol in the body.

Disulfiram is used in certain people with chronic alcoholism. This medicine can help keep you from drinking because of the unpleasant side effects that will occur if you consume alcohol while taking disulfiram.

Disulfiram is used together with behavior modification, psychotherapy, and counseling support to help you stop drinking. This medicine is not a cure for alcoholism.

Disulfiram may also be used for purposes not listed in this medication guide.

Usual Adult Dose for Alcohol Dependence:

-Initial dose: 500 mg orally once a day (this dose is generally continued for the first 1 to 2 weeks)
-Maintenance dose: 250 mg orally once a day (range: 125 mg to 500 mg once a day)
Maximum dose: 500 mg once a day
-Duration of therapy: Depending on the individual, therapy may last months or even years

Comment:
-Although usually taken in the morning, this drug may be dosed in the evening by patients who experience a sedative effect. Also, the dosage may be adjusted downward.

Use: An alcohol deterrent in the treatment of carefully selected and cooperative patients with drinking problems; its use should be accompanied by appropriate supportive treatment.

General

• Initiate therapy in a hospital or physician’s office after a complete physical examination.a

• Patient must be fully aware of therapy, thoroughly understand the disulfiram-alcohol reaction, and be supervised by regular office visits and psychotherapy.a b

Disulfiram-Alcohol Test Reaction

• Considered by most clinicians to be unnecessary and may be associated with increased drug toxicity.a

• If deemed necessary, perform only under careful medical supervision (e.g., in a hospital) and with adequate facilities (including oxygen) available for treatment of a severe reaction.a b Do not perform test reaction in patients >50 years of age.a b

• After 1–2 weeks of disulfiram therapy, slowly administer 15 mL of 100-proof whiskey (or its equivalent) to the patient; dose of alcohol may be repeated once but should not exceed 30 mL of whiskey.a b Discontinue alcohol as soon as symptoms develop.a b (See Disulfiram-Alcohol Reaction under Cautions.)

Adherence to Therapy

• Assume patients on maintenance doses who report ability to drink alcoholic beverages without symptoms are disposing of disulfiram tablets without ingesting.b Observe daily intake of tablets (preferably crushed and well mixed with liquid) before concluding disulfiram is ineffective.b

Administration

Oral Administration

Administer orally once daily, usually in the morning.b If sedation occurs, may administer at bedtime.b

Do not administer until patient has abstained from alcohol for ≥12 hours.b Never administer without the patient’s knowledge.b (See Boxed Warning.)

If adherence is a problem, administer under close supervision, preferably as crushed tablets well mixed with liquid.a b

Dosage

Adults

Initially, maximum 500 mg once daily for 1–2 weeks.a b May reduce dosage if sedation occurs.b

Average maintenance dosage: 250 mg daily (range: 125–500 mg daily) until patient is fully recovered socially and a basis for permanent self-control is established.a b Treatment may be required for months or years.a b

Prescribing Limits

Adults

Maximum 500 mg daily.a b

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.a b Use with extreme caution.b (See Hepatic Effects and also Concomitant Diseases under Cautions.)

Renal Impairment

No specific dosage recommendations at this time.a b Use with extreme caution in patients with acute or chronic nephritis.b (See Concomitant Diseases under Cautions.)

Geriatric Patients

Select dosage with caution, usually starting at low end of dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.b

In the U.S.

• Antabuse

Available Dosage Forms:

• Tablet

Therapeutic Class: Ethanol Dependency

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Eye pain or tenderness or any change in vision
• mood or mental changes
• numbness, tingling, pain, or weakness in hands or feet

• Darkening of urine
• light gray-colored stools
• severe stomach pain
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Drowsiness

• Decreased sexual ability in males
• headache
• metallic or garlic-like taste in mouth
• skin rash
• unusual tiredness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to disulfiram or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have heart problems.
• If you have psychosis.
• If you drink alcohol or take any drugs that have alcohol.
• If you are taking metronidazole.
• If you are breast-feeding. Do not breast-feed while you take disulfiram.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take disulfiram with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Disulfiram, USP is an alcohol antagonist drug.

CHEMICAL NAME

bis(diethylthiocarbamoyl) disulfide.

STRUCTURAL FORMULA

C10H20N2S4 M.W. 296.54

Disulfiram, USP occurs as a white to off-white, odorless, and almost tasteless powder, soluble in water to the extent of about 20 mg in 100 mL, and in alcohol to the extent of about 3.8 g in 100 mL.

Each tablet for oral administration contains 250 mg or 500 mg Disulfiram, USP. Tablets also contain colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and stearic acid.

No specific information is available on the treatment of overdosage with Disulfiram. It is recommended that the physician contact the local Poison Control Center.

Disulfiram Tablets USP 250 mg 100s Label Text

NDC 0093-5035-01

Disulfiram
Tablets USP
250 mg

See Side Panel for Warnings

Rx only

100 TABLETS

TEVA

• Antabuse

~1 to 2 weeks after last dose

There are no dosage adjustments provided in the manufacturer’s labeling. Use with extreme caution in hepatic cirrhosis or insufficiency.

-Initial dose: 500 mg orally once a day (this dose is generally continued for the first 1 to 2 weeks)
-Maintenance dose: 250 mg orally once a day (range: 125 mg to 500 mg once a day)
Maximum dose: 500 mg once a day
-Duration of therapy: Depending on the individual, therapy may last months or even years

Comment:
-Although usually taken in the morning, this drug may be dosed in the evening by patients who experience a sedative effect. Also, the dosage may be adjusted downward.

Use: An alcohol deterrent in the treatment of carefully selected and cooperative patients with drinking problems; its use should be accompanied by appropriate supportive treatment.

Data not available

Data not available