disulfiram (Antabuse)

Introduction

Tradename: Antabuse.

Indications

• management of alcoholics who want enforced sobriety

Contraindications

• use with caution in the elderly {potential cardiac toxicity}

pregnancy category = c

safety in lactation = ?

Dosage

Sobriety: 250-500 mg PO QD

Tabs: 250 & 500 mg.

Pharmacokinetics

• rapidly absorbed after oral administration
• metabolized by liver to:
  • diethyldithiocarbamate (t1/2 of 15 hours)
  • carbon disulfide (t1/2 of 9 hours)
• t1/2 of 7 hours
• 20% of the drug remains in the body 1 week after administration
• patients may be alcohol sensitive 1-2 weeks after the last dose taken

elimination via liver

1/2life = 7 hours

Monitor

• liver function tests at baseline, 10-14 days after initiation, then periodically

Adverse effects

• drowsiness (common, > 10%)
• fatigue
• peripheral neuritis
• blurred vision
• skin eruptions
• metallic or garlic taste
• hepatotoxicity
• mood changes
• encephalopathy (uncommon, < 1%)
• cardiac toxicity

Drug interactions

• alcohol: produces intolerance reaction
• disulfiram inhibits warfarin metabolism
• disulfiram increased phenytoin levels
• may result in psychosis/behavioral changes when used in combination with metronidazole or INH
• may result in organic brain syndrome when used in combination with tricyclic antidepressants (TCA)

Laboratory

• specimen: plasma; analyze promptly
• methods: GLC, HPLC

Mechanism of action

• inhibits aldehyde dehydrogenase resulting in accumulation of acetaldehyde
• metabolites:
  • diethyldithiocarbamate
  • carbon disulfide
• reaction with alcohol (intolerance reaction)
  • flushing
  • throbbing headache
  • nausea/vomiting
  • hypotension
  • palpitations
  • chest pain
  • blurred vision
  • confusion

More general terms

• miscellaneous pharmacologic agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3117