Disulfiram, commonly known by its brand name Antabuse, is a medication primarily used in the management of alcohol dependence or alcoholism. It works by creating an unpleasant reaction when alcohol is consumed, thus acting as a deterrent to drinking. Disulfiram is typically used as part of a comprehensive treatment program that includes counseling and support.

When a person takes disulfiram and then consumes alcohol, it inhibits the enzyme aldehyde dehydrogenase, leading to an accumulation of acetaldehyde in the body. Acetaldehyde is a toxic substance that causes symptoms such as nausea, vomiting, flushing, palpitations, and headache. These unpleasant effects serve as a deterrent to drinking alcohol while the medication is in the system.

Antabus (Disulfiram) inhibits the enzyme acetaldehyde dehydrogenase, causing sensitivity to ethanol. Severe unpleasant effects are seen immediately after alcohol intake even in small amounts.

Antabus (Disulfiram) Uses:

• Alcohol use disorder:
  • It is used in the management of chronic alcohol use disorder.

Note:

• can be considered for use in patients with alcohol use disorder (moderate to severe) who want to refrain from alcohol and either prefer disulfiram or are unable to tolerate or are non-responsive to naltrexone and acamprosate.

Antabus (Disulfiram) dose in Adults

Antabus (Disulfiram) dose in the treatment of alcohol use disorder: 

Note: It's important to remember not to take disulfiram until you've stopped drinking alcohol for at least 12 hours. Taking it while there's still alcohol in your body can cause some unpleasant side effects.

• Starting Dose: At the beginning of treatment, you might take up to 500 milligrams once a day. This usually lasts for 1 to 2 weeks.
• Regular Dose: After the first couple of weeks, the typical dose is 250 milligrams once a day. However, your doctor might adjust this based on how you're doing. The dose could range from 125 to 500 milligrams a day, but the maximum you should take in a day is 500 milligrams.

Antabus (Disulfiram) dose in Childrens

Not indicated in children.

Antabus (Disulfiram) Pregnancy Risk Category: C

• It's not clear if disulfiram is safe to use during pregnancy because there hasn't been enough research on it.
• If a pregnant woman needs treatment for alcohol withdrawal or another condition, medications should only be used if absolutely necessary, and disulfiram isn't usually the first choice for treating alcohol withdrawal.
• There are other medications that are recommended instead.
• It's essential for pregnant women to talk to their doctor about the risks and benefits of any medication they might need.

Disulfiram use during breastfeeding:

• It's uncertain whether disulfiram passes into breast milk, and the manufacturer advises against breastfeeding while using it.
• For women who are breastfeeding and need treatment for alcohol use disorder or other conditions, medications should only be used if necessary, and disulfiram isn't usually the first choice.
• There are other medications recommended for treating alcohol withdrawal in breastfeeding women.

Antabus (Disulfiram) Dose in Kidney disease:

• The manufacturer's instructions don't specify any dosage changes for people with kidney problems.
• However, if you have chronic or acute nephritis (inflammation of the kidneys), you should be extremely careful when using disulfiram.
• It's essential to discuss your kidney condition with your doctor before starting this medication, as they may want to monitor you more closely or adjust your dosage based on your kidney function.

Antabus (Disulfiram) Dose in Liver disease:

• The manufacturer's instructions don't mention any changes to the dosage for people with liver problems.
• However, if you have hepatic cirrhosis (a serious liver condition) or liver insufficiency, you should be extremely cautious when using disulfiram.
• Your doctor may want to monitor you more closely or adjust your dosage based on your liver function.

Side effects of Antabus (Disulfiram):

• Central Nervous System:
  • Bitter Taste (Garlic)
  • Drowsiness
  • Fatigue
  • Headache
  • Metallic Taste
  • Peripheral Neuritis
  • Peripheral Neuropathy
  • Polyneuropathy
  • Psychosis
• Dermatologic:
  • Acneiform Eruption
  • Allergic Dermatitis
  • Skin Rash
• Genitourinary:
  • Impotence
• Hepatic:
  • Cholestatic Hepatitis
  • Fulminant Hepatitis
  • Hepatic Failure (Multiple Case Reports)
• Ophthalmic:
  • Optic Neuritis

Contraindications to Antabus (Disulfiram):

• Disulfiram should not be used in individuals who have a hypersensitivity to disulfiram itself or any ingredient in the formulation.
• Additionally, those who are allergic to other thiuram derivatives, commonly used in pesticides and rubber vulcanization, should avoid disulfiram.
• It's crucial to avoid disulfiram if you're currently using or receiving alcohol, metronidazole (an antibiotic), paraldehyde (a sedative), or any alcohol-containing products like cough syrup or tonics, as it can lead to severe reactions.
• Furthermore, disulfiram should be avoided in individuals with psychosis or severe heart conditions such as severe myocardial disease or coronary occlusion.

Warnings and precautions

Antabus (Disulfiram), reaction:

• Consuming alcohol, even in small amounts, while taking disulfiram can lead to a range of symptoms including flushing, headache, nausea, vomiting, difficulty breathing, sweating, thirst, chest pain, rapid heartbeat, low blood pressure, fainting, weakness, dizziness, blurred vision, and confusion.
• Severe reactions may include respiratory depression, heart problems, unconsciousness, seizures, or even death.
• The severity of the reaction depends on the amount of disulfiram and alcohol taken.
• Symptoms can last from 30 minutes to several hours, or until the alcohol is metabolized.
• Patients should avoid alcohol for at least 12 hours before taking disulfiram, as reactions can occur up to 14 days after taking the medication if alcohol is consumed.

Hepatotoxicity:

• Disulfiram use has been associated with severe, sometimes fatal, liver damage and failure, including the need for liver transplantation.
• This risk exists regardless of whether the patient had previous liver problems.
• Patients should be monitored for signs of liver damage, and they should be educated about symptoms to watch for.

Cerebral damage:

• Disulfiram should be used with extreme caution in patients with brain damage or related conditions.

Contact dermatitis:

• Patients with a history of allergic reactions to thiuram derivatives (found in rubber) should be evaluated before taking disulfiram.

Diabetes:

• Disulfiram should be used with extreme caution in patients with diabetes mellitus (diabetes).

Hepatic impairment

• Extreme caution should be exercised when using disulfiram in patients with liver cirrhosis or impairment.

Hypothyroidism:

• Disulfiram should be used with extreme caution in patients with hypothyroidism (underactive thyroid).

Nephritis:

• Extreme caution is advised in patients with acute or chronic nephritis (kidney inflammation).

Seizures:

• Disulfiram should be used with extreme caution in patients with a history of seizure disorders.

Disulfiram: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Liver Function Tests:

• Baseline liver function tests should be conducted before starting disulfiram treatment.
• Liver function tests should be repeated after 10 to 14 days of starting treatment to monitor for any changes.

Complete Blood Count (CBC) and Serum Chemistries:

• CBC and serum chemistry tests may also be performed before starting disulfiram treatment to assess overall health and detect any abnormalities.

Cardiac Function Assessment:

• If clinically appropriate, cardiac function should be assessed before starting disulfiram treatment to ensure the heart is healthy enough for the medication.

How to administer Antabus (Disulfiram)?

Avoid Alcohol-Containing Medications:

• Medications containing alcohol, even topically applied ones, should not be used while taking disulfiram.

Time Restrictions:

• Disulfiram should not be administered if alcohol has been consumed within the past 12 hours to avoid a potentially severe reaction.

Preferred Administration Time:

• It is preferable to take disulfiram in the morning. However, if it causes sedation, it may be taken at bedtime.

Administration with Liquids:

• Tablets can be crushed and mixed with liquids for easier ingestion.

Mechanism of action of Antabus (Disulfiram):

• Disulfiram is a medication that stops the breakdown of alcohol in the body, leading to a buildup of a chemical called acetaldehyde.
• This buildup causes a range of unpleasant symptoms like flushing, nausea, vomiting, sweating, chest pain, and confusion when alcohol is consumed.
• These effects make it easier for people to avoid drinking alcohol and are why disulfiram is used to help treat alcohol use disorder over the long term after someone has stopped drinking.

Onset of Action:

• Full effect typically takes around 12 hours to occur after taking disulfiram.

Duration:

• The effects of disulfiram can last for approximately 1 to 2 weeks after the last dose.

Absorption:

• Disulfiram is absorbed slowly into the body.

Metabolism:

• Disulfiram is metabolized in several ways:
  • It undergoes reduction of disulfide linkage to diethyldithiocarbamic acid.
  • Further metabolism occurs through processes such as glucuronidation, non-enzymatic degradation, methylation, and oxidation.

Excretion:

• Disulfiram and its metabolites are excreted from the body through various routes:
  • Approximately 20% is excreted unchanged in feces.
  • Metabolites are also eliminated through exhaled gases.
  • About 50% of metabolites are excreted in urine.

International Brands of Disulfiram:

• Antabuse
• Alcobuse
• Alcohol Stop
• Alcolbing
• Alfiram
• Antabus
• Antabuse
• Antaethyl
• Antalcol
• Anticol
• Antietanol
• Busetal
• Chronol
• Deadict
• Difiram
• Disulfix
• Esperal
• Etabus
• Refusal
• Sarcoton
• Tetidis
• Tetradin
• Zincfrin

Disulfiram Brand Names in Pakistan: