Disulfiram Information
Disulfiram () Description
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. Disulfiram () is designated chemically as Thioperoxydicarbonic diamide ([HN)C(S)]S, tetraethyl-. The chemical structure of Disulfiram () is:
Each tablet for oral administration contains 250 mg or 500 mg Disulfiram () , USP. Tablets also contain dicalcium phosphate, hydroxypropyl cellulose, microcrystalline cellulose, polyoxy (40) stearate, sodium starch glycolate, and stearic acid.
Disulfiram () Clinical Pharmacology
Disulfiram () produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol.
Disulfiram () blocks the oxidation of alcohol at the acetaldehyde stage. During alcohol metabolism following Disulfiram () intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone.
Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the Disulfiram () -alcohol reaction. This reaction, which is proportional to the dosage of both Disulfiram () and alcohol, will persist as long as alcohol is being metabolized. Disulfiram () does not appear to influence the rate of alcohol elimination from the body.
Disulfiram () is absorbed slowly from the gastrointestinal tract and is eliminated slowly from the body. One (or even two) weeks after a patient has taken his last dose of Disulfiram () , ingestion of alcohol may produce unpleasant symptoms.
Prolonged administration of Disulfiram () does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol.
Disulfiram () 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.
Disulfiram () Contraindications
Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be given Disulfiram () .
Disulfiram () is contraindicated in the presence of severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to Disulfiram () or to other thiuram derivatives used in pesticides and rubber vulcanization.
Disulfiram () Warnings
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 () .
Disulfiram () Precautions
Patients with a history of rubber contact dermatitis should be evaluated for hypersensitivity to thiuram derivatives before receiving Disulfiram () (see ).
It is suggested that every patient under treatment carry an Identification Card stating that he is receiving Disulfiram () and describing the symptoms most likely to occur as a result of the Disulfiram () -alcohol reaction. In addition, this card should indicate the physician or institution to be contacted in an emergency. (Cards may be obtained from PAR PHARMACEUTICALS COMPANIES, INC. upon request.)
Alcoholism may accompany or be followed by dependence on narcotics or sedatives. Barbiturates and Disulfiram () have been administered concurrently without untoward effects; the possibility of initiating a new abuse should be considered.
Hepatic toxicity including hepatic failure resulting in transplantation or death have been reported. Severe and sometimes fatal hepatitis associated with Disulfiram () therapy may develop even after many months of therapy. Hepatic toxicity has occurred in patients with or without prior history of abnormal liver function. Patients should be advised to immediately notify their physician of any early symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, vomiting, jaundice, or dark urine.
Baseline and follow-up liver function tests (10 – 14 days) are suggested to detect any hepatic dysfunction that may result with Disulfiram () therapy. In addition, a complete blood count and serum chemistries, including liver function tests, should be monitored.
Patients taking Disulfiram () tablets should not be exposed to ethylene dibromide or its vapors. This precaution is based on preliminary results of animal research currently in progress that suggest a toxic interaction between inhaled ethylene dibromide and ingested Disulfiram () resulting in a higher incidence of tumors and mortality in rats. A correlation between this finding and humans, however, has not been demonstrated.
Disulfiram () Adverse Reactions
(See , and )
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 () Overdosage
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 () Dosage And Administration
Disulfiram () should never be administered until the patient has abstained from alcohol for at least 12 hours.
The average maintenance dose is 250 mg daily (range, 125 to 500 mg), it should not exceed 500 mg daily.
Note:
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 15mL (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 30mL (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.
Disulfiram () How Supplied
Disulfiram () Tablets, USP are available as follows:
250 mg are white, round, scored tablets, debossed “par-153” and supplied in bottles of 100
(NDC 49884-153-01).
500 mg are white, round, scored tablets, imprinted “par-154” and supplied in bottles of 100
(NDC 49884-154-01).
Dispense in a tight, light-resistant container as defined in the USP.
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature].
Manufactured By:
Spring Valley, New York 10977
