ANTABUS 250 mg TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Antabus 250 mg tablets

Disulfiram

Contents of the pack:

1. What is Antabus and what is it used for
2. What you need to know before you take Antabus
3. How to take Antabus
4. Possible side effects
5. Storing Antabus
6. Contents of the pack and other information

1. What is Antabus and what is it used for

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 treatment is carried out with the patient's voluntary cooperation. It is essential to have social and family support that predisposes to cessation of alcohol consumption.

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

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

2. What you need to know before you take Antabus

Do not take Antabus

• If you are allergic (hypersensitive) to disulfiram or any of the other components of Antabus.
• If you have hypersensitivity to thiuram compounds used in pesticides and vulcanization processes.
• If you have severe myocardial disease or coronary occlusion (severe heart disease).
• If you have psychotic states (psychiatric disorders).
• If you have ingested alcohol.
• If you use preparations that contain alcohol.
• If you are currently or have recently been treated with:
• • metronidazole,
  • paraldehyde or
  • medicines that contain alcohol.
• If you have severe hepatic insufficiency (severe liver disease).
• If you have severe renal insufficiency (severe kidney disease).
• If you are addicted to opiates or are being treated with opiates such as morphine, heroin, or codeine: the combined use of Antabus and opiates triggers withdrawal syndrome from the latter.
• If you are addicted to cocaine and alcohol: the combined 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 pregnant.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Antabus.

Do not take Antabus until you have been alcohol-free for at least 24 hours beforehand.

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

In the following cases, consult your doctor before starting to take Antabus:

• 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 renal insufficiency (kidney diseases).
• If you have cirrhosis or hepatic 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 analyses during treatment to monitor liver function, blood values, and biochemical parameters.

Using Antabus with other medicines

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

Especially with the following medicines:

• Propylene glycol: it can produce an increase in blood concentration and toxicity of propylene glycol.
• Hydantoin (antiepileptic and anticonvulsant medicine): it can lead to an increase in blood concentration and toxicity of hydantoins.
• Oral anticoagulants (e.g., warfarin): disulfiram can prolong prothrombin time. A dose adjustment of the anticoagulant should be assessed.
• Metronidazole (antibiotic medicine): a possible synergistic effect of both may occur, leading to acute psychotic reaction and confusion.
• Phenytoin (antiepileptic medicine): concomitant administration with phenytoin can increase blood levels of phenytoin and the possibility of phenytoin intoxication. Blood levels of phenytoin should be monitored and phenytoin adjustments made during disulfiram treatment. There is evidence that phenobarbitone is not affected by disulfiram.
• Isoniazid (medicine for the treatment of tuberculosis): an increase in the toxicity of both medicines can occur. Adverse effects associated with concomitant use of isoniazid include ataxia and changes in mood and behavior.
• Benzodiazepines (hypnotic medicines) 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 (medicine for the treatment of respiratory diseases such as asthma): it can lead to theophylline toxicity.
• Tranilcipromide (antidepressant medicine): delirium states can appear due to tranilcipromide toxicity.
• Clozapine (medicine for the treatment of schizophrenia and some psychotic disorders): disulfiram blocks the metabolism of clozapine, improving its efficacy. On the other hand, it decreases the possibility of mental disorders due to disulfiram.
• Amitriptyline (antidepressant medicine): with concomitant use with disulfiram, changes in mental status have been described.
• Rifampicin (antibiotic medicine): consult your doctor if you are being treated, as disulfiram can affect the metabolism of this medicine.
• 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 the concomitant use of disulfiram and medicines:

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

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

Taking Antabus with food and drinks

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

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

Some examples of preparations that may contain alcohol are:

• Sauces,
• Vinegar,
• Mouthwashes,
• Cough syrups,
• Aftershave preparations.

You should also be careful with low-alcohol beverages or those labeled as "alcohol-free", as taking a sufficient amount can cause unpleasant reactions.

Disulfiram-alcohol reaction

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

Redness, palpitations in the head and neck, pulsating headache, difficulty breathing, nausea, vomiting, sweating, thirst, chest pain, palpitations, shortness of breath, hyperventilation (feeling of fatigue), tachycardia (rapid heart rate), hypotension (low blood pressure), syncope (loss of consciousness), significant restlessness, weakness, dizziness, blurred vision, and confusion.

In severe reactions, there may be respiratory depression (respiratory failure), cardiovascular collapse, arrhythmias, myocardial infarction, congestive heart failure (heart disease), loss of consciousness, convulsions, and even death.

If you consume alcohol in the 3 weeks following discontinuation of 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 to several hours in most cases, or as long as there is alcohol in the blood.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

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

Breastfeeding

If you are breastfeeding, consult your doctor before using this medicine, who will decide whether it is necessary 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 using machines

Disulfiram's influence on the ability to drive and use machines is zero or insignificant. However, patients should be cautious when driving or operating machinery until they are sure that treatment with disulfiram does not cause adverse effects.

3. How to take Antabus

Follow your doctor's instructions for taking Antabus exactly. If you have any doubts, consult your doctor again.

Antabus is administered orally with a little water. Preferably, Antabus should be taken when getting up, although in patients who present sedative effects, it can be taken at bedtime.

The dosage will be established according to each case. Alternatively, to minimize the sedative effect, the initial dose can be reduced.

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

It should only be administered by a doctor. It is recommended that 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 one dose for one or two weeks. The initial dose should not exceed 500 mg (2 tablets) of disulfiram per day.

It is recommended that 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). In any case, the dose should not exceed 500 mg (2 tablets) per day.

Duration of treatment

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

Elderly patients

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 (loss of movement control), irritability, hallucinations, psychosis, loss of consciousness, and convulsions.

Death occurs due to respiratory failure, preceded by ascending paralysis and damage to 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, Telephone 915 620 420, indicating the medicine and the amount ingested.

If you forget to take Antabus

Do not take a double dose to make up for forgotten doses.

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

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

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

If you stop taking Antabus

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

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

4. Possible side effects

Like all medicines, Antabus can cause side effects, although not everybody gets 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
• Tachycardia with changes in the electrocardiogram

The following side effects may occur during treatment with Antabus:

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

• Psychiatric disorders (depression, mania)
• Somnolence, headache,
• Pain and tingling in arms and legs, muscle problems such as weakness or difficulty controlling muscles, digestion problems or even difficulty swallowing, dizziness or fainting, sexual problems such as erection problems, inability to detect the need to urinate (peripheral neuritis(1))
• Loss of vision in one eye in the course of a few hours, changes in the way the pupil reacts to bright light, loss of color vision, pain when moving the eye (optic neuritis)
• Tingling in lower limbs, pain, decreased sensitivity, muscle pain, muscle atrophy (polyneuritis).
• Nausea, vomiting, diarrhea
• Changes in liver function tests (increased transaminases and bilirubin)
• Numbness, fatigue, general malaise, halitosis (bad breath), abdominal pain, loss of taste, metallic or garlic-like taste

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

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

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

• Changes in vision
• Yellowing of the skin (jaundice)
• Decreased libido (sexual desire)

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) hepatotoxicity, hepatocellular damage, fulminant hepatitis, and (liver cell death) hepatic necrosis, which can cause liver failure, hepatic coma, and death

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

• Papillary edema (swelling in the optic papilla) characterized by blurred vision or decreased vision
• Acne-like skin rashes. Cases of phototoxicity have been described
• Erectile dysfunction (erection problems)
• Congenital malformations (fetal malformations)
• Increased cholesterol
• Hypertension (high blood pressure)

(1) Patients on maintenance treatment 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 rashes can be easily controlled by concomitant administration of an antihistamine (allergy medicine).

Reporting side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Antabus

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

Do not use Antabus after the expiration date stated on the packaging after "EXP". The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Packaging Content and Additional Information

Antabus Composition

• 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, Sodium Carboxymethylcellulose Type A (potato starch).

Product Appearance and Packaging Content

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

Marketing Authorization Holder and Manufacturer

LABORATORIOS BOHM, S.A.

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

28947 Fuenlabrada. (Madrid)

91 642 18 18

Date of the Last Revision of this Leaflet

May 2014.