PATIENT INFORMATION LEAFLET

Antabus 250 mg Tablets

Disulfiram

Antabus is indicated for the treatment of alcohol dependence (chronic alcoholism), as part of integrated rehabilitation programs.

The patient must be adequately motivated, so that the treatment is carried out with the voluntary cooperation of the patient. It is essential to have social and family support that predisposes the cessation of alcohol consumption.

Disulfiram (active principle of Antabus) acts as a deterrent to alcohol consumption in patients who need help in the treatment of chronic alcoholism.

After alcohol ingestion, it leads to acetaldehyde in the body, which is further transformed. Disulfiram blocks the enzyme that degrades acetaldehyde (aldehyde dehydrogenase) causing the accumulation of acetaldehyde in the blood. The increase in acetaldehyde concentration in the blood contributes to the reaction that appears after alcohol ingestion in patients treated with disulfiram; which consists of a series of unpleasant physical effects. This reaction is also known as the Antabus effect.

Do not take Antabus

• If you are allergic (hypersensitive) to disulfiram or any of the other components of Antabus.
• If you are hypersensitive to thiuram compounds used in pesticides and vulcanization processes.
• If you have severe myocardial disease or coronary occlusion (serious heart diseases).
• If you have psychotic states (psychiatric alterations).
• If you have ingested alcohol.
• If you use preparations containing alcohol.
• If you are currently or recently treated with:
• • metronidazole,
  • paraldehyde or
  • medications containing alcohol.
• If you have severe liver disease (serious liver disease).
• If you have severe kidney disease (serious kidney disease).
• If you are addicted to opioids or are being treated with opioids such as morphine, heroin, or codeine: the concurrent use of Antabus and opioids triggers opioid withdrawal syndrome.
• If you are addicted to cocaine and alcohol: the concurrent use of Antabus, alcohol, and cocaine increases blood levels of cocaine.
• If you are addicted to cocaine: it increases dopamine levels.
• If you are pregnant or think you may be.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Antabus.

Do not take Antabus until you have been without alcohol for at least 24 hours.

If you are being treated with disulfiram, do not be exposed to ethylene dibromide or its vapors.

Consult your doctor before starting to take Antabus in the following cases:

• If you have diabetes mellitus
• If you have hypothyroidism
• If you are epileptic.
• If you are being treated with phenytoin due to the risk of intoxication
• If you have cerebrovascular diseases.
• If you have acute and chronic nephritis or kidney insufficiency (kidney diseases).
• If you have cirrhosis or liver insufficiency (liver diseases).
• If you are being treated with oral anticoagulants, as you may need to adjust the dose.

It is recommended to perform periodic blood tests during treatment to control liver function, blood values, and biochemistry.

Use of Antabus with other medications

Inform your doctor or pharmacist if you are taking or have recently taken or may need to take any other medication, including those purchased without a prescription, homeopathic, herbal, and other health-related products.

Especially with the following medications:

• Propylene glycol: it may cause an increase in blood concentration and toxicity of propylene glycol.
• Hydantoin (antiepileptic and anticonvulsant medication): it may cause an increase in blood concentration and toxicity of hydantoins.
• Oral anticoagulants (e.g. warfarin): disulfiram may prolong prothrombin time. The dose of the anticoagulant should be adjusted.
• Metronidazole (antibiotic medication): it may cause a possible synergistic effect of both, leading to acute psychotic reaction and confusion.
• Phenytoin (antiepileptic medication): concurrent administration with phenytoin may increase phenytoin blood levels and the risk of phenytoin intoxication. Phenytoin blood levels should be monitored and adjustments made during disulfiram treatment. There is evidence that phenobarbital is not affected by disulfiram.
• Isoniazid (tuberculosis treatment medication): it may cause an increase in toxicity of both medications. Adverse effects associated with concomitant use of isoniazid include ataxia and changes in mood and behavior.
• Benzodiazepines (hypnotic medications) with oxidative metabolism (e.g. diazepam, chlordiazepoxide): the effects of these benzodiazepines but not oxazepam are increased or prolonged with concomitant use of disulfiram. Increase in blood concentration and toxicity of these benzodiazepines.
• Theophylline (medication for respiratory diseases such as asthma): it may cause toxicity of theophylline.
• Tranilcipromide (antidepressant medication): delirious states may appear due to toxicity of tranilcipromide.
• Clozapine (medication for schizophrenia and some psychotic disorders): disulfiram blocks clozapine metabolism, improving its efficacy. On the other hand, it decreases the likelihood of mental alterations due to disulfiram.
• Amitriptyline (antidepressant medication): concomitant use with disulfiram has been described to cause alterations in mental state.
• Rifampicin (antibiotic medication): consult your doctor if you are being treated, as disulfiram may affect its metabolism.
• Others. The toxicity of certain drugs has been increased in rats. Among these drugs are morphine, pethidine, amphetamine, and barbiturates.

Important interactions may occur due to concomitant use of disulfiram and drugs:

• that affect blood pressure regulation
• that act on the central nervous system.

Consult your doctor before taking antacids or iron salts, as they may affect disulfiram metabolism.

Antabus intake with food and drinks

You should avoid using alcohol in disguised forms. Some products, foods, and medications contain alcohol in their composition, so you should read the composition of these products carefully.

The disulfiram-alcohol reaction can occur even with a small amount of alcohol.

Some examples of preparations that may contain alcohol are:

• Sauces,
• Vinegar,
• Mouthwashes,
• Cough syrups,
• After-shave preparations.

You should also be particularly cautious with low-alcohol beverages or those labeled as "without alcohol," as taking a sufficient amount may cause unpleasant reactions.

Disulfiram-alcohol reaction

The effects of the disulfiram-alcohol reaction appear 10 minutes after alcohol ingestion. Even small amounts of alcohol cause this reaction, leading to:

Flush, headache, difficulty breathing, nausea, vomiting, sweating, thirst, chest pain, palpitations, shortness of breath, tachycardia, hypotension, syncope, notable restlessness, weakness, dizziness, blurred vision, and confusion.

In severe cases, there may be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, congestive heart failure, loss of consciousness, seizures, and even death.

If you consume alcohol within 3 weeks of stopping disulfiram, you may experience this reaction.

The intensity of the reaction varies from person to person, but it is generally proportional to the amount of disulfiram and alcohol ingested.

The duration of the reaction varies from 2 to 4 hours or several hours in most cases, or as long as there is alcohol in the blood.

Pregnancy, lactation, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Your doctor should evaluate the benefit-risk ratio during pregnancy and the effects of alcoholism during this period.

Lactation

If you are breastfeeding, consult your doctor before using this medication, who should decide whether to interrupt breastfeeding or interrupt treatment after considering the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Fertility

No effects on fertility have been observed.

Driving and operating machinery

The influence of disulfiram on the ability to drive and operate machinery is negligible or insignificant. However, patients should exercise caution when driving or operating machinery until they are sure that disulfiram treatment does not cause adverse effects.

Follow exactly the administration instructions for Antabus indicated by your doctor. If you have any doubts, consult your doctor again.

Antabus is administered orally with a little water. Preferably, Antabus should be taken upon rising, although in patients who experience sedative effects, it may be taken at bedtime.

The dosage will be established on a case-by-case basis. Alternatively, to minimize sedative effects, the initial dose may be reduced.

It is essential that you do not drink alcohol at least 24 hours before taking the first dose of Antabus.

It should only be administered by a doctor. It is recommended that the initial treatment with Antabus be carried out in a hospital or specialized clinics.

Adults

• Initial regimen

In the first phase of treatment, 1 to 2 tablets (250-500mg) will be administered per day in a single dose for one or two weeks. The initial dose should not exceed 500 mg (2 tablets) of disulfiram per day.

It is recommended that the initial treatment with disulfiram be carried out in a hospital or specialized clinics.

• Maintenance regimen

The maintenance dose is 250 mg per day (1 tablet). It should not exceed 500 mg (2 tablets) per day in any case.

Duration of treatment

Antabus administration should be continued daily and uninterrupted until the patient has fully reintegrated socially and a permanent self-control base has been established. Depending on the patient, maintenance treatment may be required for months or even years.

Geriatric patients

The same doses as in adults. No dose adjustment is necessary.

Use in children

No data are available, so there is no recommendation for the use of Antabus in children.

If you take more Antabus than you should

High doses of disulfiram (up to 6 g/day) have low toxicity in humans. Symptoms of overdose include vomiting, headaches, apathy, ataxia, irritability, hallucinations, psychosis, loss of consciousness, and seizures.

Death occurs due to respiratory failure, preceded by ascending paralysis and lesions in various organs (liver, spleen, kidney, central nervous system, adrenal glands, heart).

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, Teléfono 915 620 420, indicating the medication and the amount ingested.

If you forget to take Antabus

Do not take a double dose to compensate for the missed doses.

If you forget to take the dose and 12 hours or more have passed, do not take another dose.

If you do not remember whether 12 hours have passed since the last dose, do not take another dose.

In these cases, take the dose as you were taking it (at the time you should take it).

If you interrupt treatment with Antabus

Do not interrupt treatment, even if you notice improvement in symptoms. Your doctor will tell you the duration of treatment.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medicines, Antabus can cause side effects, although not everyone will experience them.

If you develop any of these signs, stop taking Antabus and talk to your doctor immediately:

• yellowing of the skin (jaundice). These are signs of liver problems.
• mental changes
• blindness
• rapid heartbeat with changes in the electrocardiogram

The following side effects may occur during treatment with Antabus:

Frequent side effects (may affect up to 1 in 10 patients):

• psychiatric changes (depression, mania)
• drowsiness, headache,
• pain and numbness in arms and legs, muscle problems such as weakness or difficulty controlling muscles, problems digesting food or even swallowing, dizziness or fainting, sexual problems such as erectile dysfunction, inability to detect the need to urinate (peripheral neuritis(1) )
• loss of vision in one eye within a few hours, changes in how the pupil reacts to bright light, loss of color vision, eye pain (optic neuritis)
• tingling in lower extremities, pain, decreased sensitivity, muscle pain, muscle atrophy (polyneuritis)
• nausea, vomiting, diarrhea
• changes in liver function tests (increased transaminases and bilirubin)
• numbness, fatigue, general discomfort, bad breath (halitosis), abdominal pain, loss of taste, metallic or garlic taste

Rare side effects (may affect up to 1 in 100 patients):

• fatigue, dystonic reactions (involuntary muscle contractions).
• skin itching, redness or inflammation of the skin, skin sensitivity, localized skin inflammation, skin rash, any type of skin lesions: redness, hives, papules (similar to pimples), vesicles and blisters (allergic dermatitis (skin lesions)(2) )

Very rare side effects (may affect up to 1 in 1,000 patients):

• changes in vision
• yellowing of the skin (jaundice)
• reduced libido (sex drive)

Very rare side effects (may affect up to 1 in 10,000 patients):

• psychotic episodes (mental changes), including paranoia, schizophrenia, mood changes
• seizures, confusion
• hepatitis (inflammatory liver disease), liver damage, fulminant hepatitis, and liver cell necrosis, which can cause liver failure, hepatic coma, and death

Side effects of unknown frequency (cannot be estimated from available data):

• papilledema (swelling of the optic disc) characterized by blurred vision or decreased vision
• skin eruptions similar to acne. Cases of phototoxicity have been reported
• erectile dysfunction (erection disorder)
• congenital malformations (fetal malformations)
• high cholesterol
• high blood pressure

(1)Patients on maintenance therapy with disulfiram 500 mg/day tend to develop peripheral neuropathy. This neuropathy improves when disulfiram treatment is discontinued.

(2)As a general rule, occasional skin eruptions are easily controlled by administering an antihistamine (allergy medication) simultaneously.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.

By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use Antabus after the expiration date that appears on the packaging after “Cad”. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Antabus

• The active ingredient is Disulfiram. Each tablet contains 250 mg of disulfiram.
• The other components are: Magnesium Stearate, Microcrystalline Cellulose PH-101, Talc, Povidone K30, Anhydrous Colloidal Silica, Dibasic Calcium Phosphate Dihydrate, Carboxymethyl Sodium Starch Type A (Potato Starch).

Appearance of the product and content of the packaging

Antabus 250 mg tablets are presented in white/PVC aluminum blisters containing 40 tablets per package.

Holder of the marketing authorization and responsible for manufacturing

LABORATORIOS BOHM, S.A.

C/ Molinaseca, 23-25. Industrial Estate Cobo Calleja.

28947 Fuenlabrada. (Madrid)

91 642 18 18

Date of the last review of this leaflet

May 2014.