disulfiram ANTABUSE
Class: Aldehyde Dehydrogenase InhibitorFDA Indications: Deterrent To Alcohol Consumption
Off-Label Use:
Prescribing
Forms: 250, 500mg tabletDose Range: 125-500 mg/day
Starting: 125 mg QPM, and to increase to 250 mg QPM after several days. Maintenance dose is usually 250 mg QPM, but some patients can drink without a reaction on this dose; if so, increase to 375 mg or 500 mg QPM.
Monitoring: Monitor LFTs
Precautions
Contraindications: Contraindicated in combination with alcohol; s/sx of a DER are due to ↑ acetaldehyde concentrations and include facial and body warmth and flushing, conjunctival injection, pruritus, urticaria, diaphoresis, lightheadedness, vertigo, headache, nausea, vomiting, and abdominal pain. Cardiac effects include dyspnea, palpitations, and chest pain.Do not give to patients with severe cardiac disease or to patients who are acutely psychotic.
Serious Side Effects: Can cause elevated liver function tests and even hepatitis. Can cause peripheral neuropathy and optic neuritis.
Side Effects: drowsiness, fatigue, headache, acne, sexual dysfunction, neuropathy, transient transaminitis (30%)
Pharmacodynamics
1° MOA: Irreversibly inhibits the oxidation of acetaldehyde, causing a considerable increase in acetaldehyde concentrations following ethanol ingestion, i.e. DER2° MOA: ↑'s [DA] by ↓ the DA-catabolizing enyzme, dopamine β-hydroxylase
Target: Aldehyde dehydrogenase, Dopamine β-hydroxylase
Pharmacokinetics
t½: 90 (60-120)° TMAX: 4-8°Substrate of: CYP3A4, 3A5, 2B6, 2E1, FMO
Inhibits: 2E1; 1A2 & 3A4 (w/ chronic use); Induces: ∅
Active Metabolites: DDC, Me-DDC
DDIs
- - do not combine with: metronidazole, paraldehyde, isoniazid, or any OTC medications that contain small amounts of alcohol, i.e. cough syrups, Nyquil
- - as a 2E1 inhibitor, can increase levels of 2E1 substrates (e.g. theophylline, halogenated inhalational anesthetic agents)
Misc
- - disulfiram is a prodrug
- - due to its long long t½, avoid alcohol for up to 14 days after treatment has been stopped
- - alcohol is rapidly metabolized, so patients can take their first dose 12 hours after their last drink
- - common advice to patients: "You'll wish you were dead but it won't kill you."
Special Populations
Category C—The lack of teratogenicity in animals and the absence of a clustering of similar birth defects in human pregnancies exposed to disulfiram suggest that this drug is not a major human teratogen. Obviously, women taking disulfiram should not drink alcohol, but this is occasionally the case because of the findings of fetal alcohol syndrome and defects that are suggestive of fetal alcohol exposure.
No reports describing the use of disulfiram during lactation have been located. Because of the relatively low molecular weight, excretion into milk should be expected. The potential effect of this exposure on a nursing infant is unknown.
Cardiovascular tolerance decreases with age, thus increasing severity of alcohol reactions
Contraindicated in severe renal disease
If baseline transaminase levels are normal or only moderately elevated (less than five times the upper limit of normal), use with careful monitoring of liver function.