Antabus - instructions for use, dose, side effects, contraindications

Excipients: corn starch 82.5 mg Povidone 2.5 mg, 12.5 mg of tartaric acid, 24 mg of sodium hydrogencarbonate, 17 mg of talc, colloidal silicon dioxide 1 mg Magnesium stearate 1 mg microcrystalline cellulose 84.5 mg.

1 tablet effervescent 400 mg contains:

active substance: disulfiram 400 mg;

Excipients: corn starch 165 mg Povidone 5 mg, 25 mg of tartaric acid, 48 mg of sodium hydrogencarbonate, 34 mg of talc, colloidal silicon dioxide 2 mg Magnesium stearate 2 mg, microcrystalline cellulose 169 mg.

Description:

For a dosage of 200 mg: Round flat tablets of white or off-white color with beveled edges, and marked with the mark "CD" on the one hand the risks and "C" on the other hand the risks.

For a dosage of 400 mg: Round flat tablets white or almost white color with beveled edges, with cross Valium dividing the tablet into four parts, and labeled "CJ" on one side.

Pharmacotherapeutic group:An agent for the treatment of alcoholism

ATX: & nbsp

N.07.B.01.01 Disulfiram

Pharmacodynamics:The effect of the drug is based on the blockade of acetaldehyde dehydrogenase, which is involved in the metabolism of ethyl alcohol. This leads to an increase in the concentration of the metabolite of ethyl alcohol - acetaldehyde, which causes negative sensations (flushing of the face, nausea, vomiting, tachycardia, lowering of blood pressure (BP), etc.), which make it extremely unpleasant to drink alcohol after taking Antabus. This leads to a conditioned reflex aversion to the taste and smell of alcoholic beverages.

Pharmacokinetics:After oral administration, the absorption of disulfiram from the gastrointestinal tract (GIT) is from 70 to 90%, is rapidly metabolized, recovering to diethyldithiocarbamate, which itself is excreted as a glucuron conjugate or converted to di-ethylamine and carbon sulphide, part of which (4- 53%) is excreted through the lungs.

Indications:Treatment and prevention of recurrences of chronic alcoholism.

Contraindications:

- Severe diseases of the cardiovascular system (including uncompensated heart failure, coronary artery disease, for example, ischemic heart disease, hypertension).

- A history of a stroke or severe organic brain damage.

- Neuropsychiatric disorders (including psychosis, risk of suicide attempts, severe forms of diseases related to personality disorder).

- Adverse reactions in the history of the liver with previous treatment with disulfiram or severe liver function (exceeding the upper limit of the norm of activity of microsomal liver enzymes in 3 times or more).

- Increased individual sensitivity to disulfiram or any auxiliary substance of the drug.

- Reception of alcoholic beverages or medicines containing ethanol, within 24 hours before taking the drug or alcohol intoxication.

- Drug dependence.

- Pregnancy or the period of breastfeeding (due to insufficient data on efficacy and safety).

- Children and adolescents under 18 years of age (due to lack of data on effectiveness and safety).

Carefully:Diabetes mellitus, hypothyroidism, signs of irreversible brain damage, kidney failure, liver or respiratory system diseases, epilepsy or convulsive syndrome of any genesis (danger moresevere disulfiram-ethanol reaction); peripheral neuropathy, peptic ulcer of the stomach and duodenum, optic neuritis (see section Side effect).

Pregnancy and lactation:Data on the effect of disulfiram on the fetus and newborn is not enough, and therefore the use of Antabus during pregnancy and breastfeeding is contraindicated. There have been reports of the development of congenital anomalies in newborns whose mothers have taken disulfiram during pregnancy.

Dosing and Administration:

The effervescent tablet is dissolved in water in an amount sufficient to completely dissolve the preparation (not less than a half-glass) and stir the resulting solution, immediately taking it inside.

Treatment is appointed after careful examination of the patient and warning of the consequences and complications.

On the first day of treatment, 800 mg of Antabus are taken. The patient should be warned that it is necessary to refrain from drinking alcohol. The next day, take 600 mg of the drug, and on the third day - 400 mg. On the fourth and fifth day, the patient should take 200 mg, and then 100-200 mg of Antabus per day or 2-3 times a week. Treatment is continued on the recommendation of the doctor until the patient's social behavior is stabilized.

The physician should assess the potential severity of the disease and the need for a disulfiram-alcohol sample. It can be prescribed starting from the fifth day of treatment.

This sample initially consists of 5 ml of ethanol (about 12 ml of alcoholic beverage, about 40% by volume) on an empty stomach.

If no reaction is observed after 20 minutes, the patient can be given another 10 ml of ethanol (about 24 ml of alcoholic beverage with a strength of about 40% by volume). At a given dose of alcohol, a positive test result rarely represents something more serious than a pronounced "tide" of blood to the skin of the face with tachycardia and in some cases a slight drop in blood pressure. If there is no reaction, then the dose of disulfiram can be increased and the test should be repeated a week before receiving a positive reaction to alcohol intake.

Side effects:

The most common non-specific adverse reactions that can be associated, including the presence of the disease itself: drowsiness, headache, reactions from the gastrointestinal tract. In case of manifestations of adverse reactions, it is possible to reduce the dose of the drug.

The incidence of adverse events was classified as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000),very rarely (<1/10000, including single cases), the frequency is unknown.

From the gastrointestinal tract: often - pain in the epigastric region, diarrhea, nausea, vomiting, smell from the mouth, metallic taste in the mouth; frequency unknown - unpleasant odor in patients with colostomy, associated with the release of carbon disulfide.

General disorders and disorders at the site of administration: often - drowsiness, fatigue, a subjective feeling of discomfort.

From the liver and bile ducts: often - increased activity of microsomal liver enzymes (transaminase and gamma- glutamyltransferase); rarely jaundice; very rarely - hepatitis, clinical manifestations of hepatotoxicity, liver cell damage, fulminant hepatitis and liver necrosis, which can lead to hepatic insufficiency, hepatic coma and death. Side effects from the liver and bile ducts usually occur during the first two months of therapy and are not dose-dependent.

From the immune system: infrequently, hypersensitivity reactions.

Laboratory and instrumental data: rarely - deviations from the norm of the results of functional tests of the liver, including an increase in the concentration of bilirubin in the blood, an increase in activity aspartate aminotransferase and alanine aminotransferase.

From the nervous system: often - drowsiness, perversion of taste, headache; rarely - peripheral neuropathy, polyneuropathy, optic neuritis, encephalopathy, tremor; rarely - convulsions, confusion. Neurological disorders, most likely, dose-dependent and usually occur through several months after the start of treatment. These effects are slowly reversible. Smokers are more predisposed to development of optic neuritis.

Disorders of the psyche: often - depression, mania; rarely - psychotic reactions (paranoia, schizophrenia); rarely - behavior change, acute organic brain syndrome.

Psychotic disorders, as a rule, occur in patients with depression or a schizophrenia in the anamnesis. These symptoms, probably related to the increase in the level of dopamine, which is the result inhibition of dopamine-beta-hydroxylase.

From the genitals and dairy glands: infrequently - decreased libido, sexual dysfunction.

From the skin and subcutaneous tissues: infrequently - acne, allergic dermatitis, skin itching, rash.

Possible side effects associated with a combination of disulfiram-ethanol:

From the heart: tazycardia, sensation palpitation, dyspnea, dizziness, arrhythmias, fainting.

From the gastrointestinal tract: vomiting.

General disorders and disorders at the site of administration: fatigue.

From the musculoskeletal system: muscle spasm.

From the nervous system: loss of consciousness, headache, impaired coordination, drowsiness.

Disorders of the psyche: apathy.

From the skin and subcutaneous tissues: increased sweating, "hot flashes" of blood to the skin of the face.

From the side of the vessels: decrease in blood pressure (BP), cardiovascular collapse.

Overdose:The combination of disulfiram-ethanol can cause oppression of consciousness up to coma, cardiovascular collapse, neurological complications. Treatment is symptomatic.

Interaction:

In addition to the effect on aldehyde dehydrogenase disulfiram inhibits other enzyme systems, including dopamine-beta-hydroxylase (which converts dopamine at norepinephrine) and microsomal enzymes of the liver.

It is possible to interact with all drugs metabolized by these enzyme systems (for example, paraldehyde, phenytoin, barbiturates, amphetamines, morphine, diazepam, chlorodiazepoxide, isoniazid, rifampicin, oral hypoglycemic agents).

Disulfiram slows down oxidation and excretion rifampicin kidneys. When used simultaneously with isoniazid may be an increase in adverse reactions from the central nervous system (dizziness, impaired coordination, irritability and insomnia).

When used simultaneously with nitroimidazole derivatives (metronidazole, secnidazole, tinidazole) there may be confusion or psychotic reactions. Isoniazid or nitroimidazole derivatives are used simultaneously with disulfiram only in case of acute necessity. In this case, the patient should be under the close supervision of a physician.

FROM ethanol there is a reaction of intolerance ("hot flushes" of blood to the skin of the face, shortness of breath, headache, palpitation, nausea, vomiting, decreased blood pressure, tachycardia, weakness or more severe reactions). When used simultaneously with amitriptyshin an increase in the reaction of intolerance to ethanol is possible. Diazepam can weaken the reaction of disulfiram-ethanol.

The reaction disulfiram-ethanol slightly weakens ascorbic acid and antihistamine preparations.

When used simultaneously with phenytoin there is a significant and rapid increase in its concentration in the blood plasma due to the inhibition of its metabolism, which leads to an increased risk of toxic effects.

If the combination can not be avoided, careful monitoring of the patient should be established, control of the concentration of phenytoin in the blood plasma during and after disulfiram treatment is necessary. If necessary, adjust the dose of phenytoin.

Strengthens the effect of indirect anticoagulants (for example, warfarin) and risk of bleeding (reduced metabolism of warfarin in the liver). It is recommended more frequent monitoring of the concentration of warfarin and correction of the dose of anticoagulants within 8 days after the cancellation of Antabus.

Disulfiram reduces metabolism theophylline. The dose of theophylline should be reduced, depending on the clinical symptoms and its concentration in the blood plasma.

Disulfiram can potentiate a sedative effect benzodiazepines by inhibiting their oxidative metabolism (especially chlordiazepoxide and diazepam).The dose of benzodiazepine should be adjusted in accordance with clinical manifestations. It is necessary to avoid the simultaneous administration of disulfiram and hepatotoxic medicines.

With simultaneous reception with pimozide in very rare cases, there was an increase in the organic brain syndrome.

Special instructions:

This drug should only be used under medical supervision.

Before starting treatment with Antabus, a determination of liver function should be performed, including the determination of the activity of microsomal liver enzymes. This examination should be carried out in the first 3 months of treatment at a frequency of at least once every two weeks, then at least every 3-6 months. When the activity of microsomal liver enzymes is increased by less than 3 times, it is necessary to evaluate the risks of using the drug and strengthen the monitoring of the patient's condition. Exceeding the upper limit of the norm of activity of microsomal enzymes of the liver 3 times or more requires immediate cessation of treatment. In this case, carefully monitor the patient prior to the normalization of the functional "hepatic" samples.

Patients should be instructed to immediately inform the attending physician of symptoms such as fatigue, anorexia (lack of appetite), nausea, vomiting, fever, itching, jaundice. darkening of the urine or discoloration of the stool, which may be symptoms of hepatitis. If they occur, stop taking the medication immediately and conduct a patient examination, including a clinical examination and a laboratory examination (assessment of the functional state of the liver).

Antabus may cause drug damage to the liver. There have been reports of fatal cases (see Side effect section).

Do not take the drug Antabus during alcohol intoxication. You can not take alcohol during treatment with Antabus, except for cases when choosing a dose by the attending physician-conducting disulfiram-ethanol sample.

When carrying out disulfiram-ethanol test in patients taking Antabus, one should be very careful. The intensity of the disulfiram-ethanol reaction depends on the dose and varies from person to person.The reaction may occur within 14 days after discontinuation of therapy with Antabus. There may be a lack of response to alcohol intake at the first time it is taken during treatment, it is also possible to manifest a reaction in a very severe form.

The drug can not be used without notifying the patient about it.

Patients should be warned about the dangers of a reaction to alcohol intolerance, which can begin 10 minutes after taking alcohol and last up to several hours. Reaction to ethanol can occur within 14 days after therapy with Antabus.

Disulfiram prevents the metabolism of ethanol, as a result of which acetaldehyde accumulates in the body, which can lead to the development of disulfiram-ethanol reaction.

Disulfiram-ethanol reaction is characterized by "hot flashes" of blood to the skin of the face, shortness of breath, headache, increased heart rate, tachycardia, lowering blood pressure, nausea and vomiting. Severe disulfiram-ethanol reactions can be manifested by the following symptoms: heart rhythm disturbances, angina attacks, collapse, myocardial infarction, sudden death, respiratory depression, neurological disorders (confusion, encephalopathy and epileptic seizures).Seldom were reported reports of deaths when taking alcohol while treating Antabus.

It is assumed that when carrying out the disulfiram-ethanol test, resources are available for carrying out measures to eliminate low blood pressure: transfer of the patient to the Trendelenburg posture, oxygenation and intravenous infusion solutions. It may be necessary to introduce pressor amines, for example, norepinephrine.

The patient and his family should be warned that some foods (for example, sauces), including products labeled "non-alcoholic" (beer, wine), as well as certain medications (such as cough syrups) may contain a slight the amount of ethanol that can provoke disulfiram-ethanol reaction. This also applies to after shaving, cosmetic products and perfumes. During the period of treatment, the patient should avoid the use and use of this product. Reaction to ethanol can be intensified by simultaneous application of amitriptyline and chlorpromazine and weakened by the intake of diazepam.

Do not drink alcohol for at least 14 days after discontinuing Antabus therapy.

Disulfiram-ethanol reaction is initiated by histamine, so that its symptoms can be masked when taking antihistamines and other drugs with antihistamine action.

When used simultaneously with indirect anticoagulants, more frequent monitoring of MHO (international normalized ratio) and correction of doses of anticoagulants at the beginning of disulfiram reception and for 8 days after its withdrawal are necessary, in connection with an increased risk of bleeding. Antibus should be taken with caution in patients with renal, hepatic insufficiency or hypothyroidism, as well as in patients with respiratory system diseases, diabetes mellitus, brain damage and epilepsy, especially at the risk of possible combination with alcohol in view of the danger of severe disulfiram-ethanol reaction.

Effect on the ability to drive transp. cf. and fur:Disulfiram can cause side reactions that affect the ability to concentrate and the speed of psychomotor reactions (including drowsiness and fatigue),therefore, during the treatment with Antabus, when these conditions appear, one should refrain from controlling vehicles and mechanisms.

Form release / dosage:Tablets effervescent 200 mg or 400 mg.

Packaging:

For 50 tablets (with a dosage of 400 mg) or 100 tablets (with a dosage of 200 mg) in a container of high-density polyethylene or a bottle of dark glass with a lid of polyethylene. 1 container with instructions for use in a cardboard box.

Storage conditions:Do not store at temperatures above 30 ° C. Keep out of the reach of children!

Shelf life:5 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005928/08

Date of registration:28.07.2008 / 14.12.2012

Expiration Date:Unlimited

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

KEMWELL BIOPHARMA, Pvt.Ltd. India

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp05.09.2017

Illustrated instructions

Instructions

Antabus® (Antabus®)