Disulfiram 250 MG Oral Tablet
: 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.
Drug Interactions: Disulfiram appears to decrease the rate at which certain drugs are metabolized and therefore may increase the blood levels and the possibility of clinical toxicity of drugs given concomitantly.
DISULFIRAM SHOULD BE USED WITH CAUTION IN THOSE PATIENTS RECEIVING PHENYTOIN AND ITS CONGENERS, SINCE THE CONCOMITANT ADMINISTRATION OF THESE TWO DRUGS CAN LEAD TO PHENYTOIN INTOXICATION.
PRIOR TO ADMINISTERING DISULFIRAM TO A PATIENT ON PHENYTOIN THERAPY, A BASELINE PHENYTOIN SERUM LEVEL SHOULD BE OBTAINED.
SUBSEQUENT TO INITIATION OF DISULFIRAM THERAPY, SERUM LEVELS OF PHENYTOIN SHOULD BE DETERMINED ON DIFFERENT DAYS FOR EVIDENCE OF AN INCREASE OR FOR A CONTINUING RISE IN LEVELS.
INCREASED PHENYTOIN LEVELS SHOULD BE TREATED WITH APPROPRIATE DOSAGE ADJUSTMENT.
It may be necessary to adjust the dosage of oral anticoagulants upon beginning or stopping disulfiram, since disulfiram may prolong prothrombin time.
Patients taking isoniazid when disulfiram is given should be observed for the appearance of unsteady gait or marked changes in mental status, the disulfiram should be discontinued if such signs appear.
In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic.
Disulfiram alone in the rat’s diet did not lead to such tumors.
The relevance of this finding to humans is not known at this time.
: 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 is an alcohol antagonist drug.
CHEMICAL NAME: bis(diethylthiocarbamoyl) disulfide.
STRUCTURAL FORMULA: C 10 H 20 N 2 S 4 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.
Disulfiram structural formula
: Disulfiram Tablets USP: 250 mg – White, round, unscored tablets, Debossed: OP 706 Bottles of 10 NDC 54868-5034-2 Bottles of 30 NDC 54868-5034-1 Bottles of 100 NDC 54868-5034-0 Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
by PLIVA Krakow Pharmaceutical Company S.A.
Krakow, Poland for Duramed Pharmaceuticals, Inc.
Subsidiary of Barr Pharmaceuticals, L.L.C.
Pomona, New York 10970 Iss.
2/2010 11001624 Relabeling and Repackaging by: Physicians Total Care, Inc.
Tulsa, Oklahoma 74146
Geriatric Use: A determination has not been made whether controlled clinical studies of disulfiram included sufficient numbers of subjects aged 65 and over to define a difference in response from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
INDICATIONS AND USAGE
: Disulfiram is an aid in the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage.
Disulfiram is not a cure for alcoholism.
When used alone, without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect on the drinking pattern of the chronic alcoholic.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Usage in Pregnancy: The safe use of this drug in pregnancy has not been established.
Therefore, disulfiram should be used during pregnancy only when, in the judgement of the physician, the probable benefits outweigh the possible risks.
Nursing Mothers: It is not known whether this drug is excreted in human milk.
Since many drugs are so excreted, disulfiram should not be given to nursing mothers.
WARNING: 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.
DOSAGE AND ADMINISTRATION
: Disulfiram should never be administered until the patient has abstained from alcohol for at least 12 hours.
Initial Dosage Schedule: In the first phase of treatment, a maximum of 500 mg daily is given in a single dose for one to two weeks.
Although usually taken in the morning, disulfiram may be taken on retiring by patients who experience a sedative effect.
Alternatively, to minimize, or eliminate, the sedative effect, dosage may be adjusted downward.
Maintenance Regimen: The average maintenance dose is 250 mg daily (range, 125 to 500 mg), it should not exceed 500 mg daily.
Note: Occasionally patients, while seemingly on adequate maintenance doses of disulfiram, report that they are able to drink alcoholic beverages with impunity and without any symptomatology.
All appearances to the contrary, such patients must be presumed to be disposing of their tablets in some manner without actually taking them.
Until such patients have been observed reliably taking their daily disulfiram tablets (preferably crushed and well mixed with liquid), it cannot be concluded that disulfiram is ineffective.
Duration of Therapy: The daily, uninterrupted administration of disulfiram must be continued until the patient is fully recovered socially and a basis for permanent self-control is established.
Depending on the individual patient, maintenance therapy may be required for months or even years.
Trial with Alcohol: During early experience with disulfiram, it was thought advisable for each patient to have at least one supervised alcohol-drug reaction.
More recently, the test reaction has been largely abandoned.
Furthermore, such a test reaction should never be administered to a patient over 50 years of age.
A clear, detailed and convincing description of the reaction is felt to be sufficient in most cases.
However, where a test reaction is deemed necessary, the suggested procedure is as follows: After the first one to two weeks’ therapy with 500 mg daily, a drink of 15 mL (1/2 oz) of 100 proof whiskey, or equivalent, is taken slowly.
This test dose of alcoholic beverage may be repeated once only, so that the total dose does not exceed 30 mL (1 oz) of whiskey.
Once a reaction develops, no more alcohol should be consumed.
Such tests should be carried out only when the patient is hospitalized, or comparable supervision and facilities, including oxygen, are available.
Management of Disulfiram-Alcohol Reaction: In severe reactions, whether caused by an excessive test dose or by the patient’s unsupervised ingestion of alcohol, supportive measures to restore blood pressure and treat shock should be instituted.
Other recommendations include: oxygen, carbogen (95% oxygen and 5% carbon dioxide), vitamin C intravenously in massive doses (1 g) and ephedrine sulfate.
Antihistamines have also been used intravenously.
Potassium levels should be monitored, particularly in patients on digitalis, since hypokalemia has been reported.