Disulfiram (Antabuse): Side Effects, Interactions, Uses & More

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Last Updated - 05/17/2024

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Updated 05/17/2024

Key Takeaways

  • Disulfiram, or Antabuse, is a medication that creates a sensitivity to alcohol by blocking the enzyme ALDH, leading to unpleasant reactions when alcohol is consumed.
  • Disulfiram’s history dates back to the 1940s when its alcohol-aversive properties were discovered accidentally in the vulcanized rubber industry.
  • Combining disulfiram with behavioral therapy is crucial for treating alcohol use disorder, as it acts as a deterrent while behavioral therapies address psychological aspects of addiction.
  • Disulfiram can cause side effects ranging from mild symptoms like headache and fatigue to severe reactions such as psychosis and liver damage.
  • Management of disulfiram’s side effects involves close monitoring by healthcare professionals, avoiding alcohol, and discussing any medical conditions that may influence the likelihood of adverse effects.
  • A disulfiram-like interaction can occur when alcohol is consumed with medications that inhibit ALDH, leading to symptoms similar to those caused by disulfiram.
  • Disulfiram can interact with substances and medications such as alcohol, antibiotics, and anticoagulants, which can lead to adverse effects.
  • Disulfiram is quickly absorbed and converted to its active form in the stomach, blocking ALDH and leading to an unpleasant reaction to alcohol.

What Is Disulfiram?

Disulfiram, commonly known by its brand name Antabuse, is a medication with a specific chemical composition that serves as an alcohol deterrent. Its primary use is in the treatment of chronic alcoholism, where it produces a sensitivity to alcohol, leading to unpleasant reactions when alcohol is consumed. 

When ingested, disulfiram blocks the enzyme aldehyde dehydrogenase (ALDH), which is involved in metabolizing alcohol in the liver. This inhibition leads to an accumulation of acetaldehyde in the blood, causing symptoms such as flushing, nausea, and palpitations if alcohol is consumed. These reactions are intended to discourage individuals from drinking alcohol while on the medication. disulfiram’s effects can persist for up to two weeks after the last dose due to its slow absorption and elimination rates.

Aside from its primary use in alcoholism treatment, disulfiram has been investigated for other potential therapeutic applications, including as a treatment for certain cancers, parasitic infections, and other conditions. However, these uses are experimental and not widely adopted in clinical practice. It’s important to note that disulfiram does not reduce alcohol cravings but acts as a deterrent by making the act of drinking alcohol unpleasant. This pharmacological strategy aims to support individuals in their recovery journey from alcohol dependence.

History of Disulfiram in Addiction Treatment

Disulfiram, commonly known by its trade name Antabuse, has a rich history dating back to the 1940s when it was discovered. Initially explored for its potential in treating parasitic infections, its unique interaction with alcohol was serendipitously uncovered in the vulcanized rubber industry, where workers exposed to a related chemical compound became ill after consuming alcohol. This discovery led researchers in Copenhagen to investigate disulfiram’s effects, which culminated in the revelation of its alcohol-aversive properties. Research during this period also tested disulfiram for treating scabies and intestinal worms.

Following these developments, disulfiram received FDA approval for the treatment of alcohol use disorder. Over the years, disulfiram has been the cornerstone of alcohol addiction treatment, although its use has been somewhat supplanted by newer pharmacotherapies like naltrexone and acamprosate. Nonetheless, disulfiram remains a significant player in addiction treatment, particularly due to its ability to produce an unpleasant hypersensitivity to alcohol, thereby discouraging alcohol consumption.

In recent times, disulfiram has been studied for its potential to treat a variety of other conditions, including cancer, parasitic infections, anxiety disorders, and latent HIV infection. Its role in the medical field continues to evolve as researchers explore disulfiram’s mechanisms and applications beyond its traditional use in alcoholism treatment, highlighting the drug’s versatility and the ongoing interest in its therapeutic potential.

Disulfiram and Behavioral Therapy in Alcohol Addiction Treatment

Combining disulfiram with behavioral therapy represents a comprehensive approach in treating alcohol use disorder (AUD). Disulfiram creates an adverse reaction to alcohol consumption, thereby supporting abstinence. Behavioral therapies, such as cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), and 12-step facilitation, are equally vital in promoting long-term recovery by addressing psychological aspects of addiction.

Research underscores the importance of combining pharmacotherapy with behavioral interventions. Disulfiram’s efficacy is enhanced when patients are aware of the potential adverse reactions to alcohol, which serves as a deterrent. Meanwhile, behavioral therapies equip patients with coping strategies and relapse prevention skills, addressing the underlying psychological triggers of addiction. A study suggested that patient-centered approaches blending elements of CBT, MET, and 12-step facilitation can lead to better outcomes when combined with medications like disulfiram.

Furthermore, a meta-analysis indicates that cognitive-behavioral therapy, when combined with pharmacotherapies, is efficacious in treating AUD. The combination is superior to usual care and brief intervention controls, with effect sizes ranging from small to moderate. This integrated treatment model is pivotal for achieving sustained recovery, reducing the risk of relapse, and improving social functioning and quality of life for individuals with AUD.

Disulfiram Side Effects

Disulfiram has a range of potential side effects ranging from mild to severe. 

Mild side effects, which often present within the first two weeks of treatment, include:

  • Headache
  • Fatigue
  • Drowsiness
  • Erectile dysfunction
  • Acne
  • Rash 
  • Metallic or garlic taste in the mouth 

These symptoms typically resolve without medical intervention. However, patients may experience more severe reactions, such as:

  • Psychosis
  • Nerve damage
  • Liver damage indicated by dark urine or jaundice

It’s essential for patients to report any severe side effects to their healthcare provider immediately.

Managing Disulfiram Side Effects

Management of disulfiram’s side effects involves close monitoring by healthcare professionals and, in some cases, adjusting the dosage or discontinuing the medication. Patients should avoid any alcohol consumption and products containing alcohol since they can worsen side effects. For safe use, patients are advised to carry an identification card indicating their use of disulfiram and to follow special dietary instructions to avoid alcohol.

The presence of certain medical conditions, such as liver or kidney disease, heart disease, diabetes, or a history of mental health disorders, may influence the likelihood of experiencing adverse effects and should be discussed with a doctor before starting treatment.

What Is a Disulfiram-Like Interaction?

A disulfiram-like interaction refers to a reaction that occurs when alcohol is consumed while taking certain medications that inhibit the enzyme aldehyde dehydrogenase (ALDH). Disulfiram is a medication used to treat alcohol use disorder that works by inhibiting ALDH. This can lead to the accumulation of acetaldehyde, a toxic byproduct of alcohol metabolism. 

Similarly, other medications can also inhibit ALDH and cause a disulfiram-like reaction when combined with alcohol. These include:

  • Metronidazole (Flagyl), an antibiotic
  • Tinidazole, an antiprotozoal
  • Trimethoprim (Bactrim), an antibiotic
  • Nitrate medications for the heart (nitroglycerin, isosorbide dinitrate) 
  • Sulfonylureas for diabetes, such as glyburide

Symptoms of a disulfiram-like reaction can include:

  • Flushing
  • Headache
  • Sweating
  • Blurred vision
  • Excessive thirst
  • Confusion
  • Anxiety
  • Weakness
  • Vertigo
  • Nausea
  • Vomiting
  • Rapid heartbeat
  • Breathing issues
  • Low blood pressure
  • Loss of consciousness

Disulfiram Drug Interactions

It’s also crucial to be aware of potential drug interactions. Disulfiram can interact with substances and medications like:

  • Alcohol
  • Amitriptyline, a tricyclic antidepressant
  • Antibiotics like metronidazole and Isoniazid
  • Anticoagulants, such as warfarin
  • Barbiturates
  • Caffeine 
  • Phenytoin, an anti-epileptic medication

Proper storage and disposal of the medication are important to prevent accidental exposure or misuse.

Disulfiram’s Pharmacokinetics

After you swallow it, disulfiram is quickly absorbed and changed, probably in the stomach, to its active form, diethyldithiocarbamate (DDC). Both the original drug and its copper compound are taken in through the stomach lining and then spread into the bloodstream.

When disulfiram and its complexes enter the bloodstream, they quickly break down into a substance called diethyldithiocarbamic acid (DDC). DDC is unstable and further breaks down into diethylamine and carbon disulphide. This breakdown is part of how the drug is processed in the body. It also includes the blocking of the enzyme aldehyde dehydrogenase (ALDH1A1), which stops the normal breakdown of alcohol. This leads to an unpleasant reaction when alcohol is consumed.

How Long Does Disulfiram Stay in the Body?

A drug’s half-life is the duration it takes for half of a single dose to be removed from the body. It typically requires five half-lives for a drug to be completely eliminated from the system. Disulfiram has a half-life of approximately 7.3 hours, which means a dose remains in the body for about 36 hours, explaining why the medication is taken once daily.

Nevertheless, the drug’s effects can lead to side effects in the body for a much longer duration. When combined with alcohol, the drug can continue to cause side effects for up to 14 days. Therefore, it is crucial to refrain from drinking while taking disulfiram unless your doctor advises you that it is safe to do so.

Factors Influencing Disulfiram’s Duration in the Body

Many factors can affect the body’s processing of disulfiram. Disulfiram is a pill taken by mouth in doses of 250–500 mg every day. When taken, 80–90% of the drug is absorbed in the stomach and intestines. This means the drug quickly enters the bloodstream, where different factors determine how long it stays in the body and how it works.

  • The dosage and frequency of administration play a crucial role. Higher doses may result in prolonged drug activity and an increased likelihood of adverse effects, as the body requires more time to metabolize and eliminate the substance.
  • Individual differences in metabolic rate can significantly affect how long disulfiram stays in the system. A faster metabolism may expedite clearance, while a slower rate may prolong its presence and effects.
  • Variations in age, weight, and gender also impact the drug’s duration within the body. These factors influence the body’s pharmacokinetic processes and can modify the metabolism and excretion rates of disulfiram.
  • Certain health conditions, particularly those affecting liver function and potential drug interactions, may alter the metabolic pathway of disulfiram, thereby influencing its systemic duration. The liver’s role in metabolizing disulfiram and the potential for enzyme inhibition or induction by concurrent medications must be considered.

Research has shown that disulfiram’s effects can last up to two weeks. However, the exact duration in the system is not precisely known and is likely subject to these individual and pharmacological variables.

Get Help for Alcohol Use Disorder Today

If you’re looking for drug & alcohol addiction treatment in Columbus or surrounding areas, you should seek out a center that offers medical detox, as opioid withdrawal symptoms can be extremely uncomfortable and potentially dangerous. It is also beneficial to seek an accredited treatment center that employs licensed addiction professionals. 

At The Recovery Village Columbus, we offer comprehensive addiction treatment in Ohio. We provide a full continuum of care, beginning with medical detox. After completing detox, patients can transition to residential treatment, partial hospitalization services or intensive outpatient care. We employ licensed and certified addiction professionals, and we are accredited by the Joint Commission, so you can rely on us for quality opioid addiction treatment. It’s time to get your life back. Call our Recovery Advocates to get started on your recovery journey. Same-day admission is often available.


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