Disulfiram
(dye SUL fi ram)
Alcoholism: Management of chronic alcoholism
Hypersensitivity to disulfiram or any component of the formulation or to other thiuram derivatives used in pesticides and rubber vulcanization; patients receiving or using alcohol, metronidazole, paraldehyde, or alcohol-containing preparations (eg, cough syrup, tonics); psychosis; severe myocardial disease or coronary occlusion.
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.
Alcoholism: Oral: Note: Do not administer until the patient has abstained from alcohol for at least 12 hours.
Initial: Up to 500 mg once daily for 1 to 2 weeks (maximum: 500 mg/day)
Average maintenance dose: 250 mg once daily (range: 125 to 500 mg/day; maximum: 500 mg/day).
Refer to adult dosing; use with caution, starting at low end of dosing range.
There are no dosage adjustments provided in the manufacturer 's labeling. Use with extreme caution in chronic and acute nephritis.
There are no dosage adjustments provided in the manufacturer 's labeling. Use with extreme caution in hepatic cirrhosis or insufficiency.
Administration of any medications containing alcohol, including topicals, is contraindicated. Do not administer disulfiram if alcohol has been consumed within the prior 12 hours. Morning administration is preferred, but may be given at bedtime if sedation is experienced. Tablets may be crushed and mixed with liquids.
Do not administer disulfiram if alcohol has been consumed within the prior 12 hours.
Store at 20 пїЅ пїЅC to 25 пїЅ пїЅC (68 пїЅ пїЅF to 77 пїЅ пїЅF). Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Antabuse: 250 mg
Antabuse: 500 mg [scored]
Generic: 250 mg, 500 mg
Alcohol (Ethyl): Disulfiram may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Avoid combination
Atazanavir: May diminish the therapeutic effect of Disulfiram. Monitor therapy
Carbocisteine: Disulfiram may enhance the adverse/toxic effect of Carbocisteine. Specifically, disulfiram may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Avoid combination
ChlordiazePOXIDE: Disulfiram may increase the serum concentration of ChlordiazePOXIDE. Monitor therapy
Chlorzoxazone: Disulfiram may decrease the metabolism of Chlorzoxazone. Monitor therapy
CYP2E1 Substrates: CYP2E1 Inhibitors (Strong) may decrease the metabolism of CYP2E1 Substrates. Consider therapy modification
DiazePAM: Disulfiram may increase the serum concentration of DiazePAM. Monitor therapy
Flunitrazepam: Disulfiram may increase the serum concentration of Flunitrazepam. Monitor therapy
Fosphenytoin: Disulfiram may increase the serum concentration of Fosphenytoin. Management: Avoid concomitant use of disulfiram and phenytoin when possible. Phenytoin dose adjustment will likely be necessary when starting and/or stopping concurrent disulfiram. Monitor phenytoin response and concentrations closely. Consider therapy modification
Isoniazid: Disulfiram may enhance the adverse/toxic effect of Isoniazid. Disulfiram may increase the serum concentration of Isoniazid. Monitor therapy
Lopinavir: May enhance the adverse/toxic effect of Disulfiram. Specifically, the combination of lopinavir/ritonavir solution, which contains 42% alcohol, may result in a disulfiram-alcohol reaction if combined. Avoid combination
MetroNIDAZOLE (Systemic): Disulfiram may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Avoid combination
MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Disulfiram. Management: Warn patients and monitor for the development of serious CNS toxicity if topical metronidazole is used in a patient taking disulfiram. Some manufacturers of vaginal metronidazole products list disulfiram use within 2 weeks as a contraindication. Consider therapy modification
Paraldehyde: Disulfiram may increase the serum concentration of Paraldehyde. Avoid combination
Phenytoin: Disulfiram may increase the serum concentration of Phenytoin. Management: Avoid concomitant use of disulfiram and phenytoin when possible. Phenytoin dose adjustment will likely be necessary when starting and/or stopping concurrent disulfiram. Monitor phenytoin response and concentrations closely. Consider therapy modification
Ritonavir: May enhance the adverse/toxic effect of Disulfiram. Specifically, the combination of ritonavir oral solution, which contains 43% alcohol, may result in a disulfiram-alcohol reaction if combined. Avoid combination
Sertraline: Disulfiram may enhance the adverse/toxic effect of Sertraline. This is specifically related to sertraline oral concentrate due to its alcohol content (12%). Management: Sertraline Oral Concentrate contains 12% alcohol, and its use should be avoided with disulfiram. Avoid combination
Theophylline Derivatives: Disulfiram may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Tinidazole: May enhance the adverse/toxic effect of Disulfiram. Avoid combination
Tipranavir: Disulfiram may enhance the adverse/toxic effect of Tipranavir. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Disulfiram may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Liver function tests (baseline and after 10 to 14 days of treatment), CBC, serum chemistries
Frequency not defined.
Central nervous system: Aftertaste (metallic or garlic-like), drowsiness, fatigue, headache, peripheral neuritis, peripheral neuropathy, polyneuropathy, psychosis
Dermatologic: Acneiform eruption, allergic dermatitis, skin rash
Genitourinary: Impotence
Hepatic: Cholestatic hepatitis, fulminant hepatitis, hepatic failure (multiple case reports)
Ophthalmic: Optic neuritis
Concerns related to adverse effects:
- Disulfiram-reaction: Ingesting alcohol, even in small amounts, during treatment with disulfiram may result in flushing, throbbing in head and neck, nausea, copious vomiting, respiratory difficulty, diaphoresis, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision and confusion. Severe reactions may involve respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, seizure and death. The intensity of the reaction is generally proportional to the amounts of disulfiram and alcohol ingested. The reaction can last from 30 minutes to several hours in more severe cases, or as long as it takes the alcohol to be metabolized.
- Hepatotoxicity: Severe (sometimes fatal) hepatitis and/or hepatic failure resulting in transplantation have been associated with use; may occur in patients with or without prior history of abnormal hepatic function. Monitor for hepatotoxicity and educate patients about signs and symptoms.
Disease-related concerns:
- Cerebral damage: Use with extreme caution in patients with cerebral damage.
- Contact dermatitis: Evaluate patients with a history of rubber contact dermatitis for hypersensitivity to thiuram derivatives before administering disulfiram.
- Diabetes: Use with extreme caution in patients with diabetes mellitus.
- Hepatic impairment: Use with extreme caution in patients with hepatic cirrhosis or impairment.
- Hypothyroidism: Use with extreme caution in patients with hypothyroidism.
- Nephritis: Use with extreme caution in patients with acute or chronic nephritis.
- Seizures: Use with extreme caution in patients with a history of seizure disorder.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Alcohol intoxication: [US Boxed Warning]: Should never be administered to a patient when he/she is in a state of alcohol intoxication, or without his/her knowledge. The physician should instruct relatives accordingly.
- Patient information: Patients must receive appropriate counseling, including information on the disulfiram reaction, "disguised " пїЅ forms of alcohol (eg, tonics, mouthwashes, cough mixtures, sauces, vinegars, aftershave lotions, back rubs) and the duration of the drugs activity (up to 14 days).
Safety in pregnancy has not been established; there is limited data on maternal use during pregnancy (Reitnauer,1997).
Disulfiram is a thiuram derivative which blocks the oxidation of alcohol at the acetaldehyde stage. When taken concomitantly with alcohol, there is an increase in serum acetaldehyde levels. High acetaldehyde causes uncomfortable symptoms including flushing, throbbing in head and neck, nausea, vomiting, diaphoresis, thirst, palpitations, chest pain, dyspnea, hyperventilation, tachycardia, syncope, weakness, blurred vision, confusion, vertigo, and hypotension. This reaction is the basis for disulfiram use in post-withdrawal long-term care of alcoholism.
Slow
Reduction of disulfide linkage to diethyldithiocarbamic acid, then further metabolized via glucuronidation, non-enzymatic degradation, methylation and oxidation (Eneanya 1981)
Feces (20% unchanged) and exhaled gases (as metabolites), urine (50% metabolites). (Eneanya 1981)
Full effect: 12 hours
~1 to 2 weeks after last dose
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, loss of strength and energy, sexual dysfunction, acne, headache, or change in taste. Have patient report immediately to prescriber vision changes, burning or numbness feeling, mood changes, behavioral changes, or signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.