Disulfiram: Difference between revisions

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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 1-(diethylthiocarbamoyldisulfanyl)- N,N-diethyl-methanethioamide
|authorTag=
| CAS_number = 97-77-8
 
| ATC_prefix = N07
{{VP}}
| ATC_suffix = BB01
<!--Overview-->
| ATC_supplemental = {{ATC|P03|AA04}}
 
| PubChem = 3117
|genericName=
| DrugBank = APRD00767
 
| C=10 | H=20 | N=2 | S=4
 
| molecular_weight = 296.543 g/mol
 
| bioavailability =  
|aOrAn=
| protein_bound =  
 
| metabolism = [[Hepatic]] to diethylthiocarbamate
a
| elimination_half-life = 60-120 hours
 
| pregnancy_category = C <small>(US)</small>
|drugClass=
| legal_status =  
 
| routes_of_administration = Oral
 
}}
 
{{SI}}
|indication=
{{CMG}}
 
selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage
 
|hasBlackBoxWarning=
 
|adverseReactions=
 
 
 
<!--Black Box Warning-->
 
|blackBoxWarningTitle=
Title
 
|blackBoxWarningBody=
<i><span style="color:#FF0000;">ConditionName: </span></i>
 
* Content
 
<!--Adult Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Adult)-->
 
|fdaLIADAdult=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
* Dosing Information
 
:* Dosage
 
=====Condition3=====
 
* Dosing Information
 
:* Dosage
 
=====Condition4=====
 
* Dosing Information
 
:* Dosage
 
<!--Off-Label Use and Dosage (Adult)-->
 
<!--Guideline-Supported Use (Adult)-->
 
|offLabelAdultGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
 
|offLabelAdultNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
 
|fdaLIADPed=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
 
|offLabelPedGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
 
|offLabelPedNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Contraindications-->
 
|contraindications=
 
*Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be given disulfiram.
 
*Disulfiram is contraindicated in the presence of severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization.
 
<!--Warnings-->
 
|warnings=
 
* Description
 
====Precautions====
 
* Description
 
<!--Adverse Reactions-->
 
<!--Clinical Trials Experience-->
 
|clinicalTrials=
 
There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
 
=====Body as a Whole=====
 
 
 
 
=====Cardiovascular=====
 
 
 
 
=====Digestive=====
 
 
 
 
=====Endocrine=====
 
 
 
 
=====Hematologic and Lymphatic=====
 
 
 
 
=====Metabolic and Nutritional=====
 
 
 
 
=====Musculoskeletal=====
 
 
 
 
=====Neurologic=====
 
 
 
 
=====Respiratory=====
 
 
 
 
=====Skin and Hypersensitivy Reactions=====
 
 
 
 
=====Special Senses=====
 
 
 
 
=====Urogenital=====
 
 
 
 
=====Miscellaneous=====
 
 
 
<!--Postmarketing Experience-->
 
|postmarketing=
 
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
 
=====Body as a Whole=====
 
 
 
=====Cardiovascular=====
 
 
 
=====Digestive=====
 
 
 
=====Endocrine=====
 
 
 
=====Hematologic and Lymphatic=====
 
 
 
=====Metabolic and Nutritional=====
 
 
 
=====Musculoskeletal=====
 
 
 
=====Neurologic=====
 
 
 
=====Respiratory=====
 
 
 
=====Skin and Hypersensitivy Reactions=====
 
 
 
=====Special Senses=====
 
 
 
=====Urogenital=====
 
 
 
=====Miscellaneous=====
 
 
 
<!--Drug Interactions-->
 
|drugInteractions=
 
* Drug
:* Description
 
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|useInPregnancyFDA=
* '''Pregnancy Category'''
 
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
 
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There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
 
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|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
 
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
 
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
 
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
 
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
 
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
 
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
 
<!--Administration and Monitoring-->
 
|administration=
 
* Oral
 
* Intravenous
 
|monitoring=
 
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
* Description
 
<!--IV Compatibility-->
 
|IVCompat=
 
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
 
<!--Overdosage-->
 
|overdose=
 
===Acute Overdose===
 
====Signs and Symptoms====
 
* Description
 
====Management====
 
* Description
 
===Chronic Overdose===
 
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
 
<!--Pharmacology-->
 
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*
 
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*
 
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
<!--Pharmacodynamics-->
 
|PD=
 
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
 
<!--Pharmacokinetics-->
 
|PK=
 
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
 
<!--Nonclinical Toxicology-->
 
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There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
 
<!--Clinical Studies-->
 
|clinicalStudies=
 
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
 
<!--How Supplied-->
 
|howSupplied=
 
*


==Overview==
<!--Patient Counseling Information-->
'''Disulfiram''' is a [[medication|drug]] used to support the treatment of chronic [[alcoholism]] by producing an acute sensitivity to [[ethanol|alcohol]]. Trade names for disulfiram in different countries are '''Antabuse''' and '''Antabus''' manufactured by Odyssey Pharmaceuticals. Disulfiram is also being studied as a treatment for [[cocaine]] dependence, as it prevents the breakdown of [[dopamine]] (a neurotransmitter whose release is stimulated by cocaine); the excess dopamine results in increased anxiety, higher blood pressure, restlessness and other unpleasant symptoms.  Several studies have reported that it has anti-protozoal activity as well.<ref name="pmid9624499">{{cite journal |author=Nash T, Rice WG |title=Efficacies of zinc-finger-active drugs against Giardia lamblia |journal=Antimicrob. Agents Chemother. |volume=42 |issue=6 |pages=1488–92 |year=1998 |pmid=9624499 |doi=}}</ref><ref name="pmid10052908">{{cite journal |author=Bouma MJ, Snowdon D, Fairlamb AH, Ackers JP |title=Activity of disulfiram (bis(diethylthiocarbamoyl)disulphide) and ditiocarb (diethyldithiocarbamate) against metronidazole-sensitive and -resistant Trichomonas vaginalis and Tritrichomonas foetus |journal=J. Antimicrob. Chemother. |volume=42 |issue=6 |pages=817–20 |year=1998 |pmid=10052908 |doi=}}</ref>


==Interaction with alcohol==
|fdaPatientInfo=
Under normal [[metabolism]], alcohol is broken down in the [[liver]] by the [[enzyme]] [[alcohol dehydrogenase]] to [[acetaldehyde]], which is then converted by the enzyme [[acetaldehyde dehydrogenase]] to the harmless [[acetic acid]].  Disulfiram blocks this reaction at the intermediate stage by blocking the enzyme acetaldehyde dehydrogenase.  After alcohol intake under the influence of disulfiram, the concentration of acetaldehyde in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone.  As acetaldehyde is one of the major causes of the symptoms of a "[[hangover]]" this produces immediate and severe negative reaction to alcohol intake. Some 5-10 minutes after alcohol intake, the patient may experience the effects of a severe [[hangover]] for a period of 30 minutes up to several hours. Symptoms include [[flushing]] of the skin, accelerated heart rate, [[shortness of breath]], [[nausea]], and [[vomiting]].


Disulfiram should not be taken if alcohol has been consumed in the last 12 hours. There is no tolerance to disulfiram: the longer it is taken, the stronger its effects. As disulfiram is absorbed slowly through the digestive tract and eliminated slowly by the body the effects may last for up to 2 weeks after the initial intake; consequently, [[medical ethics]] dictate that patients must be fully informed about the disulfiram-alcohol reaction.  Possible side effects while taking Disulfiram are numbness or tingling of the lower legs and shortness of breath.
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


==Dosage==
<!--Precautions with Alcohol-->
Disulfiram is supplied in 200 mg, 250 mg and 500 mg tablets.  The usual initial dose is 500 mg for 1 to 2 weeks, followed by a maintenance dose of 250 mg (range 125 mg - 500 mg) per day.  The total daily dosage should not exceed 500 mg.


==History and Antiprotozoal use==
|alcohol=
The drug's action was discovered by accident in 1948 by the researchers Erik Jacobsen and Jens Hald at the Danish drug company Medicinalco. The substance was intended to provide a remedy for parasitic infestations; however, workers testing the substance on themselves reported severe symptoms after alcohol consumption.


A study reported that it may be potentially useful in the treatment of ''[[Giardia]]'' infection.<ref name="pmid9624499" />    Another study found that it had activity against ''[[Trichomonas vaginalis]]'' which was resistant to the most common treatment, [[Metronidazole]].<ref name="pmid10052908" /> 
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


== Similarly acting substances ==<!-- This section is linked from [[Edible mushroom]] -->
<!--Brand Names-->
Coprine (N5-1-hydroxycyclopropyl-L-glutamine) which metabolises to 1-aminocyclopropanol, a closely-related chemical having the same metabolic effects, occurs naturally in several edible [[mushroom]] species, such as the [[Coprinopsis atramentaria|Common Ink Cap]].


Temposil, or citrated calcium carbamide, has the same function as disulfiram, but is weaker and safer.
|brandNames=


== Dangerous drug interactions ==
* ®<ref>{{Cite web | title = | url =  }}</ref>
Disulfiram should not be administered to patients who take certain stimulant drugs and antidepressants.  Disulfiram has been found to inhibit the enzyme dopamine-beta-hydroxylase, blocking the metabolism of [[dopamine]] into [[norepinephrine]]. Combined with the [[dopamine]] agonist and/or [[reuptake]] effect of [[stimulant]]s, this can cause a dramatic rise in synaptic dopamine levels, resulting in sleeplessness, paranoia, and, in extreme cases, stimulant psychosis.


Drugs that are known to interfere with the dopamine / norepinephrine system include, but are not limited to:
<!--Look-Alike Drug Names-->


*[[Bupropion]] (Wellbutrin IR/SR/XL, Buspar, Amfebutamone)
|lookAlike=
*[[Amphetamine]]s (Adderall, Dexedrine, etc.)
*[[Methylphenidate]] (Ritalin, Concerta, Focalin, etc.)
*[[Cocaine]] (Occasionally used in dental procedures, and a known substance of abuse.)


The metabolism of other drugs may be inhibited by disulfiram, increasing their potential for toxic effects.  Drugs known to have adverse effects when used concurrently with disulfiram include [[amitriptyline]], [[isoniazid]], and [[metronidazole]] (all with acute changes in mental state), [[phenytoin]], some [[benzodiazepines]], [[morphine]], [[pethidine]], and [[barbiturates]].
* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>


==Organic chemistry==
<!--Drug Shortage Status-->
Disulfiram is an example of a thiuram [[disulfide]], that is the oxidized derivative of [[diethyldithiocarbamate]].


== See also ==
|drugShortage=
*[[Naltrexone]]
}}


==References==
<!--Pill Image-->
{{Reflist|2}}


{{Drugs used in addictive disorders}}
{{PillImage
{{Ectoparasiticides}}
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|NDC=
|drugAuthor=
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[[Category:Antiprotozoal agents]]
<!--Label Display Image-->
[[Category:Abuse]]
[[Category:Drug]]
[[Category:Thiuram disulfides]]


{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}


{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}


{{WH}}
<!--Category-->


{{WS}}
[[Category:Drug]]

Revision as of 15:44, 18 December 2014

Disulfiram
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Disulfiram is a that is FDA approved for the {{{indicationType}}} of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1
  • Dosing Information
  • Dosage
Condition2
  • Dosing Information
  • Dosage
Condition3
  • Dosing Information
  • Dosage
Condition4
  • Dosing Information
  • Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Disulfiram in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Disulfiram in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Disulfiram in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Disulfiram in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Disulfiram in pediatric patients.

Contraindications

  • Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be given disulfiram.
  • Disulfiram is contraindicated in the presence of severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization.

Warnings

  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Disulfiram in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Disulfiram in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Disulfiram in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Disulfiram during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Disulfiram with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Disulfiram with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Disulfiram with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Disulfiram with respect to specific gender populations.

Race

There is no FDA guidance on the use of Disulfiram with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Disulfiram in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Disulfiram in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Disulfiram in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Disulfiram in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Disulfiram in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Disulfiram in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Disulfiram in the drug label.

Pharmacology

There is limited information regarding Disulfiram Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Disulfiram in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Disulfiram in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Disulfiram in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Disulfiram in the drug label.

How Supplied

Storage

There is limited information regarding Disulfiram Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Disulfiram |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Disulfiram |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Disulfiram in the drug label.

Precautions with Alcohol

  • Alcohol-Disulfiram interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)


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