1. Name Of The Medicinal Product
Antabuse® tablets 200 mg.
Disulfiram tablets 200 mg.
2. Qualitative And Quantitative Composition
Each tablet contains 200 mg disulfiram.
3. Pharmaceutical Form
Tablets.
4. Clinical Particulars
4.1 Therapeutic Indications
Alcohol deterrent compound. Disulfiram may be indicated as an adjuvant in the treatment of carefully selected and co-operative patients with drinking problems. Its use must be accompanied by appropriate supportive treatment.
4.2 Posology And Method Of Administration
Adults and elderly patients only:
It is recommended that treatment with Disulfiram should be initiated only in a hospital or specialised clinic and by physicians experienced in its use. The patient should have adequate social and family support to avoid ingestion of alcohol. Suitable patients should not have ingested alcohol for at least 24 hours and must be warned that a Disulfiram-alcohol reaction is potentially dangerous.
On the first day of treatment, the patient should be given no more than 4 tablets of Disulfiram in one dose (800 mg). The next day the patient should take 3 tablets followed on the third day by 2 tablets and on the fourth and fifth days by 1 tablet. Subsequently, daily dosing should continue at 1 or half a tablet daily for as long as advised by the physician but no longer than six months without review.
In the routine management of the alcoholic it is not recommended to carry out an alcohol challenge test. If the clinician feels an alcohol challenge test is essential for the success of the therapy, full information of the procedure and risks of this test can be obtained from the company. As severe reactions can occur any alcohol challenge should be carried out in specialised units by physicians acquainted with the procedure. Full resuscitation facilities must be immediately available.
Children:
Not applicable.
4.3 Contraindications
Presence of cardiac failure, coronary artery disease, previous history of CVA, hypertension, severe personality disorder, suicidal risk or psychosis.
4.4 Special Warnings And Precautions For Use
Caution should be exercised in the presence of renal failure, hepatic or respiratory disease, diabetes mellitus and epilepsy.
Before initiating treatment it is advised that appropriate examinations should be carried out to establish the suitability of the patient for treatment. Patients must not ingest alcohol during or for 1 week after ceasing Disulfiram therapy. Patients must be warned of the unpredictable and potentially severe nature of a Disulfiram-alcohol reaction as, in rare cases deaths have been reported following the drinking of alcohol by patients receiving Disulfiram. Certain foods, liquid medicines, remedies, tonics, toiletries, perfumes and aerosol sprays may contain sufficient alcohol to elicit a Disulfiram-alcohol reaction and patients should be made aware of this. Caution should also be exercised with low alcohol and “non-alcohol” or “alcohol-free” beers and wines, which may provoke a reaction when consumed in sufficient quantities. All personnel involved in the administration of Disulfiram to the patient know that Disulfiram should not be given during a drinking episode.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Disulfiram blocks the metabolism of alcohol and leads to an accumulation of acetaldehyde in the blood stream. The Disulfiram-alcohol reaction can occur within 10 minutes of ingestion of alcohol and may last several hours. It is characterised by intense flushing, dyspnoea, headache, palpitations, tachycardia, hypotension, nausea and vomiting.
Supportive therapy should be available and measures may be necessary to counteract hypotension. Severe vomiting might occur requiring administration of intravenous fluids.
Disulfiram may potentiate the toxic effects of warfarin, antipyrine, phenytoin, chlordiazepoxide and diazepam by inhibiting their metabolism. Animal studies have indicated similar inhibition of metabolism of pethidine, morphine and amphetamines. A few case reports of increase in confusion and changes in affective behaviour have been noted with the concurrent administration of metronidazole, isoniazid or paraldehyde. Potentiation of organic brain syndrome and choreoatphetosis following pimozide have occurred very rarely. The intensity of the Disulfiram-alcohol reaction may be increased by amitriptyline and decreased by diazepam. Chlorpromazine while decreasing certain components of the Disulfiram-alcohol reaction may increase the overall intensity of the reaction. Disulfiram inhibits the oxidation and renal excretion of rifampicin.
4.6 Pregnancy And Lactation
Pregnancy: The use of Disulfiram in the first trimester of pregnancy is not advised. The risk/benefit ratio in assessing adverse effects of alcoholism in pregnancy should be taken into account when considering the use of Disulfiram in pregnant patients.
There have been rare reports of congenital abnormalities in infants whose mothers have received Disulfiram in conjunction with other medicines.
Lactation: Should not be used. No information is available on whether Disulfiram is excreted in breast milk. Its use during breast feeding is not advised especially where there is a possibility of interaction with medicines that the baby may be taking.
4.7 Effects On Ability To Drive And Use Machines
Presumed to be safe or unlikely to produce an effect.
4.8 Undesirable Effects
During initial treatment, drowsiness and fatigue may occur, nausea, vomiting, halitosis and reduction in libido have been reported. If side effects are marked the dosage may be reduced. Psychotic reactions, including depression, paranoia, schizophrenia and mania occur rarely in patients receiving Disulfiram. Allergic dermatitis, peripheral neuritis and hepatic cell damage have also been reported.
4.9 Overdose
Disulfiram alone has low toxicity. Reports of the ingestion of quantities of up to 25 g refer to central and peripheral neurological symptoms which have resolved without sequel. Treatment should be symptomatic, gastric lavage and observation are recommended.
Disulfiram blocks the metabolism of alcohol and leads to an accumulation of acetaldehyde in the blood stream. The Disulfiram-alcohol reaction can occur within 10 minutes of ingestion of alcohol and may last several hours. It is characterised by intense flushing, dyspnoea and vomiting.
Supportive therapy should be available and measures may be necessary to counteract hypotension. Severe vomiting might occur requiring administration of intravenous fluids.
Symptoms: Vomiting, headache, drowsiness, fatigue, apathy, ataxia.
Treatment: Gastric lavage. Observation. Disulfiram by itself has low toxicity.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
The effect of Disulfiram is primarily due to irreversible inactivation of liver ALDH. In the absence of this enzyme, the metabolism of ethanol is blocked and the intracellular acetaldehyde concentration rises. The symptoms of the Disulfiram-alcohol reaction (DAR) are due partly to the high levels of acetaldehyde. The conversion of dopamine to noradrenaline is also inhibited and the depletion of noradrenaline in the heart and blood vessels allows acetaldehyde to act directly on these tissues to cause flushing, tachycardia and hypotension.
In addition to its affect on acetaldehyde dehydrogenase, disulfiram inhibits other enzyme systems including dopamine-beta-hydroxylase (which converts dopamine and noradrenaline) and hepatic microsomal mixed function oxidases (which are responsible for the metabolism of many drugs). Disulfiram may thus potentiate the action of drugs which are metabolised by these enzymes.
5.2 Pharmacokinetic Properties
Following oral administration, absorption is variable, distribution is primarily to the kidney, pancreas, liver, intestines and fat. Disulfiram is rapidly metabolised to diethyldithiocarbamic acid (DDC), is conjugated with glucuronic acid, oxidised to sulphate, methylated and decomposed to diethylamine and carbon disulphide. Excretion is primarily through the kidneys.
5.3 Preclinical Safety Data
None.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose, potato starch, povidone, microcrystalline cellulose, polysorbate 20, tartaric acid, colloidal anhydrous silica, sodium bicarbonate, maize starch, magnesium stearate.
6.2 Incompatibilities
None.
6.3 Shelf Life
3 years.
6.4 Special Precautions For Storage
Store below 25°C in a dry place and keep tightly closed. Protect from light.
6.5 Nature And Contents Of Container
Polyethylene container with a polyethylene screw cap tamper evident closure, pack size of 50 tablets.
6.6 Special Precautions For Disposal And Other Handling
Not applicable.
7. Marketing Authorisation Holder
Actavis Group PTC ehf
Reykjavikuvegi 76-78
220 Hafnarfjordur
Iceland.
8. Marketing Authorisation Number(S)
PL 30306/0036
9. Date Of First Authorisation/Renewal Of The Authorisation
16 August 1994
10. Date Of Revision Of The Text
24 September 2007
No comments:
Post a Comment