Disulfiram

disulfiram

(dye sul' fi ram)

Antabuse

Pregnancy Category C

Drug classes

Antialcoholic drug

Enzyme inhibitor

Therapeutic actions

Inhibits the enzyme aldehyde dehydrogenase, blocking oxidation of alcohol and allowing acetaldehyde to accumulate to concentrations in the blood 5–10 times higher than normally achieved during alcohol metabolism; accumulation of acetaldehyde produces the highly unpleasant reaction described below that deters consumption of alcohol.

Indication

·        Aids in the management of selected chronic alcoholics who want to remain in a state of enforced sobriety

Contraindications and cautions

·        Contraindicated with allergy to disulfiram or other thiuram derivatives used in pesticides and rubber vulcanization, severe myocardial disease or coronary occlusion; psychoses, current or recent treatment with metronidazole, paraldehyde, alcohol, alcohol-containing preparations (eg, cough syrups, tonics), pregnancy.

·        Use cautiously with diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic and acute nephritis, hepatic cirrhosis or dysfunction.

Available forms

Tablets—250 mg.

Dosages

Never administer to an intoxicated patient or without patient's knowledge. Do not administer until patient has abstained from alcohol for at least 12 hr.

ADULTS

·        Initial dosage: Administer maximum of 500 mg/day PO in a single dose for 1–2 wk. If a sedative effect occurs, administer hs or decrease dosage.

·        Maintenance regimen: 125–500 mg/day PO. Do not exceed 500 mg/day. Continue use until patient is fully recovered socially and a basis for permanent self-control is established.

·        Trial with alcohol (do not administer to anyone > 50 yr): After 1–2 wk of therapy with 500 mg/day PO, a drink of 15 mL of 100 proof whiskey or its equivalent is taken slowly. Dose may be repeated once, if patient is hospitalized and supportive facilities are available.

Pharmacokinetics

Route	Onset	Peak	Duration
Oral	Slow	12 hr	1–2 wk

Metabolism: Hepatic; T_1/2: Unclear

Distribution: Crosses placenta; enters breast milk

Excretion: Feces, lungs

Adverse effects

Disulfiram with alcohol

·        Flushing, throbbing in head and neck, throbbing headaches, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitations, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, confusion; severe reactions may include arrhythmias, CV collapse, acute CHF, unconsciousness, seizures, MI, death

Disulfiram alone

·        CNS: Drowsiness, fatigability, headache, restlessness, peripheral neuropathy, optic or retrobulbar neuritis

·        Dermatologic: Skin eruptions, acneiform eruptions, allergic dermatitis

·        GI: Metallic or garliclike aftertaste, hepatotoxicity

Interactions

Drug-drug

·        Increased serum levels and risk of toxicity of phenytoin and its congeners, diazepam, chlordiazepoxide

·        Increased therapeutic and toxic effects of theophyllines and caffeine

·        Increased PT caused by disulfiram may lead to a need to adjust dosage of oral anticoagulants

·        Severe alcohol-intolerance reactions with any alcohol-containing liquid medications (eg, elixirs, tinctures)

·        Acute toxic psychosis with metronidazole

Nursing considerations

Assessment

·        History: Allergy to disulfiram or other thiuram derivatives; severe myocardial disease or coronary occlusion; psychoses; current or recent treatment withmetronidazole, paraldehyde, alcohol, alcohol-containing preparations (eg, cough syrups, tonics); diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic and acute nephritis, hepatic cirrhosis or dysfunction; pregnancy

·        Physical: Skin color, lesions; thyroid palpation; orientation, affect, reflexes; P, auscultation, BP; R, adventitious sounds; liver evaluation; LFTs, renal function tests, CBC, SMA-12

Interventions

·        Do not administer until patient has abstained from alcohol for at least 12 hr.

·        Administer orally; tablets may be crushed and mixed with liquid beverages.

·        Monitor LFTs before, in 10–14 days, and every 6 mo during therapy to evaluate for hepatic dysfunction.

·        Monitor CBC, SMA-12 before and every 6 mo during therapy.

·        Inform patient of the seriousness of disulfiram-alcohol reaction and the potential consequences of alcohol use. Disulfiram should not be taken for at least 12 hr after alcohol ingestion, and a reaction may occur up to 2 wk after disulfiram therapy is stopped; all forms of alcohol must be avoided.

·        Arrange for treatment with antihistamines if skin reaction occurs.

·        WARNING: Institute supportive measures if disulfiram-alcohol reaction occurs; oxygen, carbon dioxide combination, massive doses of vitamin C IV, ephedrine have been used.

Teaching points

·        Take drug daily; if drug makes you dizzy or tired, take it at bedtime. Tablets may be crushed and mixed with liquid.

·        Abstain from forms of alcohol (beer, wine, liquor, vinegars, cough mixtures, sauces, aftershave lotions, liniments, colognes, liquid medications). Using alcohol while taking this drug can cause severe, unpleasant reactions—flushing, copious vomiting, throbbing headache, difficulty breathing, even death.

·        Wear or carry a medical ID while you are taking this drug to alert any medical emergency personnel that you are taking it.

·        Have periodic blood tests while taking drug to evaluate its effects on the liver.

·        You may experience these side effects: Drowsiness, headache, fatigue, restlessness, blurred vision (use caution driving or performing tasks that require alertness); metallic aftertaste (transient).

·        Report unusual bleeding or bruising, yellowing of skin or eyes, chest pain, difficulty breathing, ingestion of any alcohol.

Adverse effects in Italic are most common; those in Bold are life-threatening.