DISULFIRAM

DISULFIRAM (dye-sul'fi-ram) Antabuse, Cronetal, Ro-sulfiram Classifications: enzyme inhibitor; antialcohol agent; Therapeutic: alcohol abuse deterrant Pregnancy Category: B

Availability

250 mg, 500 mg tablets

Action

Acts as a deterrent to alcohol ingestion by inhibiting the enzyme acetaldehyde dehydrogenase, which normally metabolizes alcohol in the body.

Therapeutic Effect

When a small amount of alcohol is ingested, a complex of highly unpleasant symptoms known as the disulfiram reaction occurs, which serves as a deterrent to further drinking.

Uses

Adjunct in treatment of the patient with chronic alcoholism who sincerely wants to maintain sobriety.

Contraindications

Severe myocardial disease; cardiac disease; psychosis; patients who have recently ingested alcohol, metronidazole, paraldehyde; multiple drug dependence.

Cautious Use

Diabetes mellitus; epilepsy; seizure disorders; hypothyroidism; coronary artery disease, cerebral damage; chronic and acute nephritis; renal disease; hepatic cirrhosis or insufficiency; abnormal EEG; pregnancy (category B), lactation.

Route & Dosage

Alcoholism Adult: PO 500 mg/d for 1–2 wk, then 125–500 mg/d (max: 500 mg/d)

Administration

Oral

• Give daily dose in the morning when the resolve not to drink may be strongest.
• Give at bedtime to minimize sedative effect of the drug. Decrease in dose may also reduce sedative effect.
• Make sure patient has abstained from alcohol and alcohol-containing preparations for at least 12 h and preferably 48 h before initiating therapy.
• Determine compliance periodically. Maintenance therapy may be required for months or even years.
• Store at 15°–30° C (59°–86° F) unless otherwise directed. Protect tablets from light.

Adverse Effects (≥1%)

Reaction with alcohol ingestion: Flushing of face, chest, arms, pulsating headache, nausea, violent vomiting, thirst, sweating, marked uneasiness, confusion, weakness, vertigo, blurred vision, pruritic skin rash, hyperventilation, abnormal gait, slurred speech, disorientation, confusion, personality changes, bizarre behavior, psychoses, tachycardia, palpitation, chest pain, hypotension to shock level arrhythmias, acute congestive failure. Severe reactions: Marked respiratory depression, unconsciousness, convulsions, sudden death. Body as a Whole: Hypersensitivity (allergic or acneiform dermatitis; urticaria, fixed-drug eruption). CNS: Drowsiness, fatigue, restlessness, headache, tremor, psychoses (usually with high doses), polyneuritis, peripheral neuropathy, optic neuritis. GI: Mild GI disturbances, garlic-like or metallic taste, hepatotoxicity, hypersensitivity hepatitis.

Diagnostic Test Interference

Disulfiram can reduce uptake of I¹³¹; or decreases PBI test results (rare).

Interactions

Drug: Alcohol (including in liquid OTC drugs, IV nitroglycerin, IV cotrimoxazole), metronidazole, paraldehyde will produce disulfiram reaction; isoniazid can produce neurological symptoms; may increase blood levels and toxicity of warfarin, paraldehyde, barbiturates, phenytoin.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Onset: Up to 12 h. Duration: Up to 2 wk. Distribution: Initially deposited in fat. Metabolism: Metabolized slowly in liver. Elimination: 5–20% excreted in feces; 20% remains in body for 1–2 wk; some may be excreted in breath as carbon disulfide.

Nursing Implications

Assessment & Drug Effects

• Do a complete physical examination and careful drug history prior to initiation of therapy.
• Lab tests: Baseline and follow-up transaminase studies every 10–14 d to detect hepatic dysfunction, and perform CBC and sequential multiple analysis (SMA-12) tests every 6 mo.
• Note: Disulfiram reaction occurs within 5–10 min following ingestion of alcohol and may last 30 min to several hours. Intensity of reaction varies with each individual, but is generally proportional to the amount of alcohol ingested.
• Treat patient with severe disulfiram reaction as though in shock. Monitor potassium levels, especially if patient has diabetes mellitus.

Patient & Family Education

• Understand fully the possible dangers if alcohol is ingested during disulfiram treatment before consenting to therapy.
• Report promptly to physician the onset of nausea with right upper quadrant pain or discomfort, itching, jaundiced sclerae or skin, dark urine, clay-colored stools. Withhold drug pending liver function tests.
• Note: Ingestion of even small amounts of alcohol or use of external applications that contain alcohol may be sufficient to produce a reaction. Read all labels and avoid use of anything containing alcohol.
• Prolonged administration of disulfiram does not produce tolerance; the longer the therapy, the higher the sensitivity to alcohol.
• Alcohol sensitivity may last as long as 2 wk after disulfiram has been discontinued.
• Note: Adverse effects of drug are often experienced during first 2 wk of therapy; symptoms usually disappear with continued therapy or with dose reduction.
• Carry an identification card stating you are on disulfiram therapy and describing the symptoms of disulfiram reaction. Also provide the name of the physician or institution to contact in an emergency.
• Do not drive or engage in other potentially hazardous activities until response to drug is known.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug