Teturam (Tablets) Instructions for Use

ATC Code

N07BB01 (Disulfiram)

Active Substance

Disulfiram (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug for the treatment of alcohol dependence

Pharmacotherapeutic Group

Remedy for the treatment of alcoholism

Pharmacological Action

A drug for the treatment of alcohol dependence. It has an inhibitory effect on the enzyme aldehyde dehydrogenase, which is involved in the metabolism of ethanol.

This leads to an increase in the concentration of the ethanol metabolite, acetaldehyde, which causes facial flushing, nausea, vomiting, general malaise, tachycardia, and decreased blood pressure, making alcohol consumption extremely unpleasant after taking disulfiram.

Pharmacokinetics

After oral administration, the active substance is rapidly but incompletely (70-90%) absorbed from the gastrointestinal tract.

Due to its high lipid solubility, Disulfiram is widely distributed in the body and accumulates in various fat depots.

Disulfiram is rapidly metabolized to diethyldithiocarbamate (DDC), which is partially excreted as carbon disulfide in exhaled air and partially metabolized in the liver to methyl-DDC.

The latter is converted into an active metabolite, the methyl ester of diethylthiocarbamic acid (methyl-DTC).

C_max of methyl-DTC in blood plasma is reached 4 hours after taking disulfiram, but the maximum inhibitory activity against aldehyde dehydrogenase is first observed after 3 days of administration.

The T_1/2 of methyl-DTC is about 10 hours, while the inhibitory activity against aldehyde dehydrogenase lasts significantly longer.

The effect can thus persist for 7-14 days after discontinuation.

With mild or moderate impairment of liver function, metabolism does not change.

In contrast, in liver cirrhosis, an increase in the concentration of metabolites in the blood is observed.

Metabolites are mainly excreted in the urine.

A part is excreted in exhaled air as carbon disulfide.

20% is excreted unchanged through the intestines.

Up to 20% of the dose may remain in the body for 1 week or more.

Indications

Treatment and prevention of relapses of chronic alcoholism; as a detoxifying agent for chronic nickel poisoning.

ICD codes

Dosage Regimen

Administer orally as tablets.

Initiate therapy only after a minimum 24-hour alcohol-free period.

The typical adult dosage ranges from 125 mg to 500 mg once daily.

Determine the exact dose, regimen, and treatment duration individually under strict medical supervision.

For initial treatment, a higher dose may be used, followed by a gradual reduction to a lower maintenance dose.

Perform baseline liver function tests before starting treatment.

Monitor liver transaminase levels monthly, especially during the first three months of therapy.

Adjust the dosage with caution in patients over 60 years of age.

Discontinue therapy and re-evaluate if signs of hepatic impairment or severe neuropathy occur.

Warn the patient that the disulfiram-ethanol reaction can occur for up to 14 days after the last dose.

Ensure the patient fully understands the serious risks associated with alcohol consumption during treatment.

Adverse Reactions

From the digestive systemoften – dysgeusia (taste disturbance), infrequently – abnormal stool odor; with long-term use of disulfiram – gastritis.

From the liver and biliary tract:frequency unknown – hepatic failure, fulminant hepatitis, hepatitis (predominantly cytolytic).

From the nervous systemvery often – headache; often – drowsiness, infrequently – polyneuropathy; frequency unknown – optic neuritis, seizures, amnesia, encephalopathy; with long-term use of disulfiram – exacerbation of polyneuritis.

From the psyche:frequency unknown – neuropsychiatric disorders, confusion; with long-term use of disulfiram – psychoses resembling alcoholic psychoses.

From the cardiovascular system:frequency unknown – arterial hypertension; with long-term use of disulfiram in patients with cardiovascular diseases, cerebral vascular thrombosis is possible.

From the skin and subcutaneous tissuesfrequency unknown – allergic dermatitis.

Othervery often – asthenia.

Reactions due to the Disulfiram-ethanol associationfrequency unknown – seizures, cerebral edema, subdural hemorrhage; tachycardia, arrhythmia, angina pectoris, myocardial infarction (sometimes fatal), facial skin flushing, decreased blood pressure, cardiovascular collapse; respiratory depression; nausea, vomiting; erythema; general malaise.

When taking ethanol in doses of more than 50-80 ml (calculated as 40% ethanol) while taking disulfiram, severe disorders of the cardiovascular and respiratory systems, edema, and seizures develop.

In this case, detoxification and symptomatic therapy are urgently carried out.

Contraindications

Hypersensitivity to disulfiram; severe hepatic failure, severe respiratory failure, severe renal failure, diabetes mellitus, history of stroke or severe organic brain lesions, neuropsychiatric disorders, epilepsy and convulsive syndrome of any origin, cardiovascular diseases, including coronary artery disease; intake of alcoholic beverages or medicinal products containing ethanol within the previous 24 hours; pregnancy and childbearing age (in the absence of contraception), breastfeeding period; age under 18 years; simultaneous use of isoniazid, metronidazole, ornidazole, secnidazole, tinidazole, phenytoin.

With caution renal insufficiency (risk of developing a more severe Disulfiram-ethanol reaction), hypothyroidism (risk of developing a more severe Disulfiram-ethanol reaction), nickel dermatitis (increased risk of developing hepatitis), gastric and duodenal ulcer, optic neuritis, in patients taking cocaine (risk of QT interval prolongation); patients over 60 years of age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency. Should be used with caution in patients with liver diseases.

Use in Renal Impairment

Contraindicated in severe renal failure. Should be used with caution in patients with renal insufficiency (risk of developing a more severe Disulfiram-ethanol reaction).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age (due to lack of data on efficacy and safety).

Geriatric Use

Should be prescribed with caution to elderly patients to avoid worsening of concomitant diseases.

Special Precautions

Disulfiram should be used only under medical supervision.

Cases of severe toxic liver damage (including fulminant hepatitis and liver necrosis) have been reported, which can lead to liver failure, hepatic coma and death or require liver transplantation.

Before starting treatment with disulfiram, liver function tests, including determination of liver transaminase activity, should be performed.

Such tests should be repeated regularly during the use of disulfiram, especially in the first 3 months of treatment (monthly).

Should be used with caution in patients with renal insufficiency, respiratory diseases.

During the use of disulfiram, the intake of alcoholic beverages and medicines containing ethanol should be avoided.

Effect on the ability to drive vehicles and operate machinery

Special attention should be paid to the issue of the possibility of driving vehicles and working with machinery due to the risk of developing drowsiness associated with taking disulfiram.

Drug Interactions

The intake of alcoholic beverages and ethanol-containing medicines should be avoided during treatment with disulfiram to prevent the development of reactions due to the Disulfiram-ethanol association.

When used concomitantly, Disulfiram increases the risk of behavioral and coordination disorders.

With simultaneous use of disulfiram with nitroimidazole derivatives (metronidazole, ornidazole, secnidazole, tinidazole), acute delirium and confusion are possible.

With simultaneous use of disulfiram with phenytoin, a significant and rapid increase in plasma concentrations of phenytoin occurs, leading to an increased risk of toxic effects (Disulfiram inhibits the metabolism of phenytoin).

With simultaneous use of disulfiram and hepatotoxic drugs, liver damage is possible.

With simultaneous use of disulfiram with warfarin and other indirect anticoagulants, the anticoagulant effect is enhanced and the risk of bleeding increases (decreased metabolism of warfarin in the liver).

Disulfiram reduces the metabolism of theophylline. When used simultaneously, dose adjustment of theophylline is necessary.

With simultaneous use, the concentration of diazepam and chlordiazepoxide in blood plasma increases, in some cases accompanied by dizziness.

Under the influence of diazepam, a decrease in the intensity of the Disulfiram-ethanol reaction is possible. A case of increased toxicity of temazepam has been described.

With simultaneous use of disulfiram with tricyclic antidepressants, phenothiazine derivatives, MAO inhibitors, there is a risk of developing serious adverse reactions associated with drug interaction.

Disulfiram inhibits liver enzymes, so when used simultaneously with drugs metabolized in the liver, their metabolism may be impaired.

A case of mania development in a patient taking Disulfiram and buspirone has been described.

With simultaneous use, the clearance of desipramine and imipramine from the body decreases.

With simultaneous use with amitriptyline, an enhancement of the therapeutic effect of disulfiram is possible, but an enhancement of the toxic effect of amitriptyline on the central nervous system is also possible.

With simultaneous use with isoniazid, cases of dizziness and depression have been described; with caffeine – the excretion of caffeine from the body decreases; with metronidazole – acute psychosis and confusion develop; with omeprazole – a case of impaired consciousness and catatonia has been described.

With simultaneous use with perphenazine, the development of psychotic symptoms cannot be excluded.

With simultaneous use, Disulfiram inhibits the metabolism and excretion of rifampicin.

With simultaneous use with phenazone, the T_1/2 of phenazone increases; with phenytoin – the effects of phenytoin are enhanced due to an increase in its plasma concentration, toxic reactions develop.

With simultaneous use with chlorzoxazone, the concentration of chlorzoxazone in blood plasma increases; with chlorpromazine – increased arterial hypotension is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.