Aversion Therapy - Alcoholism Drug Therapy

.
You are being asked to take part in AAT. You will be asked to sign this agreement which states
that the AAT has been explained, that your questions have been answered, and that you agree to
participate.
The treating doctor will explain about AAT/Disulfirm tablet. He or she will explain how the AAT
will be carried out and what you will be expected to do. The treating doctor will also explain the
possible risks and possible benefits of taking AAT. You should ask the treating doctor any
questions you have about any of these things before you decide whether you wish to take part in
the AAT.
Please read the form and talk to the treating doctor about any questions you may have. Then, if
you decide to take part in the AAT, please sign and date this form in front of the person who
explained the study to you. You will be given a copy of this form to keep.

About Disulfiram:
Disulfiram (Chemical name: Bis(diethylthiocarbamoyl, Trade name: Antabuse®)
disulfide.)was the first medication approved by the U.S. Food and Drug Administration (FDA) to
treat chronic alcohol dependence. In its pure state, disulfiram is a white to off-white, odorless,
almost tasteless powder, which is soluble in water and alcohol. Disulfiram, an alcohol-aversive
or alcohol-sensitizing agent, causes an acutely toxic physical reaction when mixed with alcohol.
Continuing research and clinical findings have clarified disulfiram's mode of action and
established its safe and effective use in the treatment of alcohol use disorders (AUDs) in some
patient groups.
Dosage/How taken:

Dosage:
Standard dosage information for disulfiram.

Initial dosage 250 mg/day in 1 morning or evening dose for 1–2 weeks

Average maintenance dosage 250 mg/day

Dosage range 125–500 mg/day

Maximum dosage 500 mg/day

Additional dosage information includes the following:

 Patients who experience sedation with disulfiram to take it at bedtime. If daytime
sedation persists, adujust in dosage downward is done.
 If a patient can drink alcohol without problems when compliant with the routine starting
dose (which is rare), increase the dosage (dosage may be increased up to 500 mg/day
with careful monitoring). Never exceed 500 mg/day.
 Patients who miss a dose to take it as soon as they remember. However, if it is almost
time for the next dose, they should skip the missed dose.
Patients never to take a double dose of disulfiram Tablet by mouth once daily (also may be
crushed and mixed with water, coffee, tea, milk, soft drink, or fruit juice).
How supplied: Bottles of 100 or 1,000 250 mg tablets or bottles of 50, 100, or 500 500 mg
tablets.
Storage: Keep out of reach of children; keep tightly closed in original container; store at room
temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard
when outdated or no longer needed.
Pharmacokinetics:
Disulfiram is a prodrug.
Absorption of disulfiram from the gastrointestinal tract is rapid but incomplete and
approximately 20% is excreted in the faeces. Because of its high lipid solubility,
disulfiram is widely distributed and accumulated in various fat depots. Disulfiram is
rapidly metabolised to diethyldithiocarbamate (DDC), which is partly excreted as carbon
disulfide in the expired air and is partly metabolised in the liver to Me-DDC. Me-DDC is
metabolised further to the active metabolite Me-DTC (diethylthiocarbaminic acid methyl
ester). The concentration of Me-DTC reaches its maximum after about four hours, but
the maximum enzyme inhibiting effect (aldehyde dehydrogenase (ALDH)) is first
reached after three daily doses. The plasma half-life for Me-DTC is about ten hours, but
the enzyme inhibiting effect of ALDH lasts considerably longer. The effect can thus
persist for 7 to 14 days after discontinuation. In patients receiving disulfiram
maintenance treatment, the ingestion of alcohol brings about a typical disulfiram-alcohol
reaction within the course of five to ten minutes. Metabolism is not appreciably affected
by a mild to moderate decrease in hepatic function. The metabolites are chiefly excreted
with the urine. A part is recovered in the expired air as carbon disulfide.
Up to 20% of a dose may remain in the body for one week or longer.
It is possible that Antabuse tablets may be more bioavailable when given with food.

Side Effects of Disulfurm:

In addition to its needed effects, some unwanted effects may be caused by disulfiram. In
the event that any of these side effects do occur, they may require medical attention.
Severity: Moderate
If any of the following side effects occur while taking disulfiram, check with your
doctor or nurse as soon as possible:

Less common:
 Eye pain or tenderness or any change in vision

 mood or mental changes

 numbness, tingling, pain, or weakness in hands or feet
Rare
 Darkening of urine
 light gray-colored stools
 severe stomach pain
 yellow eyes or skin

Minor Side Effects

Some of the side effects that can occur with disulfiram may not need medical attention.
As your body adjusts to the medicine during treatment these side effects may go away.
Your health care professional may also be able to tell you about ways to reduce or
prevent some of these side effects. If any of the following side effects continue, are
bothersome or if you have any questions about them, check with your health care
professional:

More common:
 Drowsiness

Less common or rare:

 Decreased sexual ability in males

 headache
 metallic or garlic-like taste in mouth
 skin rash
 unusual tirednessFind Lowest Prices

Symptoms of Disulfiram-Induced Hepatic Impairment

Excessive tiredness Vomiting
Weakness Yellowness of the skin/eyes
Lack of energy Dark urine
Loss of appetite Fever
Upset stomach Light-colored stools

Disulfiram Cautions:

Patient Condition or Circumstance Treatment Recommendation

History of cardiac disease, diabetes mellitus, Use with caution. No evidence exists that
hypothyroidism, epilepsy, cerebral damage, patients with preexisting liver disease are
chronic or acute nephritis, hepatic cirrhosis, or more likely to suffer severe hepatotoxicity
hepatic insufficiency from disulfiram therapy.

Patients with hepatitis C According to current available evidence, if

baseline transaminase levels are normal or
only moderately elevated (less than five times
the upper limit of normal), use with careful
monitoring of liver function.

Children and adolescents Safety and efficacy for children has not been
determined. One study indicates that
disulfiram can be safe and effective with
adolescents .Administer with caution.

Patients receiving or who have recently received Do not use disulfiram until substances are out
metronidazole, paraldehyde, alcohol, or alcohol- of the patient's system.
containing preparations (e.g., cough syrups,
tonics); also patients exposed to ethylene
dibromide or its vapors (e.g., in paint, paint
thinner, varnish, shellac)

Patients using products that contain alcohol in Instruct patients to test any alcohol-containing
disguised forms (e.g., vinegars, sauces, product before using it by applying some to a
aftershave lotions, liniments) small area of the skin for 1 to 2 hours. If there
is no redness, itching, or unwanted effects, the
product may be used safely.

Age 61 or older Dosages may need to be decreased.

 How to use disulfiram:

 See also Precautions section.

 Take this medication by mouth with or without food, usually once daily in the
morning or as directed by your doctor. If this medication causes drowsiness, take
it at bedtime.
 Dosage is based on your medical condition and response to therapy. The
maximum recommended daily dose is 500 milligrams.
 Use this medication regularly to get the most benefit from it. To help you
remember, take it at the same time each day.
 This is not a complete list of possible side effects. If you notice other effects not
listed above, contact your doctor .
 Call your doctor for medical advice about side effects.

Precautions:

 Before taking disulfiram, tell your doctor or pharmacist if you are allergic to it; or
to thiuram or thiuram-related chemicals (found in pesticides and rubber); or if you
have any other allergies. This product may contain inactive ingredients, which
can cause allergic reactions or other problems. Talk to your pharmacist for more
details.
 This medication should not be used if you have certain medical conditions.
Before using this medicine, consult your doctor or pharmacist if you have: severe
heart/blood vessel disease (e.g., coronary artery disease), certain mental/mood
condition (psychosis).
 Before using this medication, tell your treating doctor/Clinical staff your medical
history, especially of: diabetes, underactive thyroid (hypothyroidism), brain
disorders (e.g., seizures, brain damage), kidney disease, liver disease, personal
or family history of regular use/abuse of drugs.
 Avoid all alcoholic beverages or alcohol-containing products/foods (e.g., cough
and cold syrups, mouthwash, aftershave, sauces, vinegars) while taking this
medication and for 2 weeks after stopping the medication. Check all product
labels carefully to make sure that there is no alcohol in the product. Using
alcohol, even a small amount, while taking this medication can lead to a reaction
that may include flushing, throbbing headache, breathing problems (e.g.,
shortness of breath, fast breathing), nausea, vomiting, dizziness, extreme
tiredness, fainting, fast/irregular heartbeat, or blurred vision. These symptoms
can last from 30 minutes to several hours. Tell your doctor right away if these
symptoms occur, especially if they persist or worsen.
 A more serious reaction with this medication and alcohol may include trouble
breathing, seizures, loss of consciousness, chest/jaw/left arm pain. Seek
immediate medical attention if you have these symptoms.
 During pregnancy, this medication should be used only when clearly needed.
Discuss the risks and benefits with your doctor.
  It is unknown if this drug passes into breast milk. Consult your treating doctor
before breast-feeding.

Do not administer Antabuse until the patient has abstained from alcohol for at least 24
hours.

 Patients who stop taking Antabuse should be advised to wait at least one week before
taking alcohol and that reactions with alcohol may occur for up to three weeks after
ingesting disulfiram
 Interactions
 Your doctor or pharmacist may already be aware of any possible drug
interactions and may be monitoring you for them. Do not start, stop, or change
the dosage of any medicine before checking with your doctor first.
 This drug should not be used with the following medications because very
serious interactions may occur: alcohol-containing products (e.g., cough and cold
syrups, aftershave), metronidazole.
 If you are currently using any of these medications listed above, tell your doctor
before starting disulfiram.
 Before using this medication, tell your doctor of all prescription and
nonprescription/herbal products you may use, especially of: amitriptyline, "blood
thinners" (e.g., warfarin), certain medications for seizures (e.g., hydantoins such
as phenytoin/fosphenytoin), isoniazid, theophylline.
 This medication can increase the side effects of caffeine. Avoid drinking large
amounts of beverages containing caffeine (coffee, tea, colas) or eating large
amounts of chocolate.
 This medication may interfere with certain laboratory tests (including urine
VMA/HVA tests), possibly causing false test results. Make sure laboratory
personnel and all your doctors know you use this drug.
 Before using this product, tell your doctor of all the products you use. Keep a list
of all your medications with you, and share the list with your doctor .

Drug Interactions With Disulfiram:

Drug Effect With Disulfiram Recommended Action

Benzodiazepines Decreases plasma clearance of Substitute oxazepam (Serax®) or

Chlordiazepoxide chlordiazepoxide or diazepam lorazepam (Ativan®)
(Librium®)
Diazepam (Valium®)

Isoniazid May cause unsteady gait, changes Discontinue disulfiram if either effect
in mental state is noted
Drug Effect With Disulfiram Recommended Action

Rifampin (Rifadin®, If used with isoniazid to treat Adjust dosages as needed

Rimactane®) tuberculosis, see isoniazid effects
above

Metronidazole Leads to a greater likelihood of Do not prescribe disulfiram and

(Flagyl®) confusion or psychosis metronidazole concomitantly

Oral anticoagulant Inhibits warfarin metabolism Adjust dosages as needed

(e.g., warfarin
[Coumadin®])

Oral hypoglycemic Produces disulfiram-like Monitor carefully if prescribing oral

reactions with alcohol hypoglycemics and disulfiram
concomitantly

Phenytoin (Dilantin®) Increases serum levels through Obtain baseline phenytoin serum
CYP 450 2C9 inhibition level before disulfiram therapy;
reevaluate level during therapy;
adjust dosage if phenytoin level
increases

Theophylline Increases serum levels through Obtain baseline theophylline serum

CYP 450 1A2 inhibition level before disulfiram therapy;
reevaluate level during therapy;
adjust dosage if theophylline serum
level increases

Tricyclic May cause delirium with Adjust dosages, discontinue

antidepressants, concurrent administration disulfiram, or switch to another class
®
amitriptyline (Elavil ) of antidepressant medication

Desipramine Decreases total body clearance Monitor closely; adjust dosages if

®
(Norpramin ), and increases elimination half- needed
imipramine (Tofranil®) life and peak plasma levels of
desipramine or imipramine
.
The disulfiram-ethanol reaction:
Disulfiram inhibits the enzyme system responsible for the conversion of acetaldehyde to
acetate. The ingestion of ethanol subsequent to the administration of disulfiram results
in raised blood acetaldehyde levels with accumulation in the tissues producing the so
called `aldehyde reaction'. Note that the aldehyde reaction can occur 10 to 14 days after
discontinuation of disulfiram, and possibly up to three weeks after discontinuation.
A disulfiram-ethanol toxic reaction is heralded by an intense cutaneous flushing from the
head downwards, involving the face, sclera, upper limbs and chest. The cutaneous
flushing is caused by vasodilatation and is accompanied by a sensation of heat and
sweating, and palpitations, with tachycardia, dyspnoea, hyperventilation and the
development of a pounding headache. There is a feeling of constriction and irritation of
the throat and trachea, resulting in spasms of coughing. Chest pains may occur
simulating coronary spasm. Restlessness or a sense of uneasiness and fear of dying
may develop. These symptoms are accompanied by a steep rise in blood pressure,
followed by hypotension if vasodilatation is significant. Flushing is then replaced by
pallor, weakness, vertigo, and nausea develops that turns into violent vomiting with
abdominal cramps. Other symptoms reported include thirst, dizziness, blurred vision,
numbness of hands and feet, and insomnia. Severe reactions may affect the heart, and
there may be convulsions, loss of consciousness, and death from cardiorespiratory
failure.
The intensity of the reaction varies with each individual, but is generally proportional to
the amounts of disulfiram and ethanol ingested. Mild reactions may occur in the
sensitive individual when the blood ethanol concentration is increased to as little as 5 to
10 mg/100 mL. Symptoms are fully developed at 50 mg/100 mL, and unconsciousness
usually results when the blood ethanol level reaches 125 to 150 mg/100 mL.
The duration of the reaction varies from two to four hours to several hours in the more
severe cases, or as long as there is ethanol in the blood. Confusion, drowsiness and
sleep usually follow. Frequently, there are transient ECG changes, such as flattening of
T waves, depression of the ST segment, and QT prolongation in a pattern suggestive of
right ventricular strain.

Interactions:
Concomitant ingestion of antacids containing divalent cations may reduce absorption.
Large doses of ferrous salts similarly block absorption.
Disulfiram blocks the oxidation and renal excretion of rifampicin.
Disulfiram may retard the metabolism of certain drugs and thus prolong the duration of
action or increase the possibility of clinical toxicity of drugs given concomitantly. The
drugs include phenytoin and its congeners, and isoniazid.
Isoniazid. The adverse reactions associated with concurrent use of isoniazid include
ataxia and changes in mental state.
Phenytoin. Concurrent use with phenytoin may increase serum levels of phenytoin and
possibly lead to phenytoin intoxication. Phenytoin serum levels should be carried out
and dosage adjustments of phenytoin may have to be made during concurrent therapy
with Antabuse tablets. There is evidence that phenobarbitone is not affected by
disulfiram.
Benzodiazepines. The effects of chlordiazepoxide and diazepam, but not oxazepam
are increased and prolonged by the concurrent use of disulfiram.
Anticoagulants. Since disulfiram may prolong prothrombin time, it may be necessary to
adjust dosage of oral anticoagulants, e.g. warfarin, in patients receiving these drugs.
Metronidazole. Acute psychotic reaction and confusion can result.
Paraldehyde. Concurrent use, theoretically may cause a modified disulfiram-ethanol
reaction, and is not recommended.

What you should do about this interaction:

Avoid drinking alcohol while taking this medicine. Avoid the use of products that contain
alcohol. The amount of alcohol required to cause this interaction varies among patients. Use of
topical products such as creams or lotions that contain alcohol may also cause this
interaction.Contact your doctor for more information. Your healthcare professionals may be
aware of this interaction and may be monitoring you for it. Do not start, stop, or change your
medicine or diet before checking with them first.

Who is Appropriate for Treatment with Disulfiram:

 Patients motivated for treatment and committed to total abstinence

 Patients capable of understanding the consequences of drinking alcohol while taking
disulfiram
 Medically appropriate patients
 Patients who can receive supervised dosing
 Patients who are abstinent from alcohol
 Patients who maintain abstinence during treatment
Patients who are codependent on or also abuse cocaine.
Patients with severely impaired judgment or who are highly impulsive from a severe mental
illness or cognitive impairment may be inappropriate candidates for treatment with disulfiram.

Before Initiating Treatment With Disulfiram:

Physicians should not administer disulfiram until the following steps have been taken:
 Educate the patient about disulfiram and obtain informed consent.
 Wait until the patient has abstained from alcohol at least 12 hours and/or breath or blood
alcohol level is zero.
 Perform a physical exam, baseline liver and kidney function tests, and a pregnancy test
for women. Perform an electrocardiogram if clinically indicated (e.g., history of heart
disease).
  Complete a medical and psychiatric history. Determine allergies to disulfiram or other
drugs; prescription and nonprescription medications taken, including vitamins; history of
cardiovascular disease, diabetes, thyroid disease, seizure disorder, central nervous system
impairment, or kidney or liver disease; and for women, reproductive status, including
current pregnancy or plans to become pregnant or to breast-feed.

Adverse Reactions to Disulfiram and Their Management

Adverse Reaction Management

Optic neuritis Usually diagnosed after patient complains of visual disturbance.
Discontinue disulfiram and conduct an ophthalmologic examination.

Peripheral neuritis, Usually diagnosed after patient complains of paresthesias (numbness

polyneuritis, peripheral or tingling). Discontinue disulfiram and observe patient or arrange for
neuropathy neurological evaluation.

Hepatitis, including When symptoms of hepatic dysfunction are reported or observed

cholestatic and (see Exhibit 3-5), perform a medical history and physical examination
fulminant hepatitis, as and obtain followup liver function tests. When clinical or laboratory
well as hepatic failure* evidence of hepatic dysfunction is found, discontinue disulfiram
immediately. Maintain clinical monitoring of symptoms and liver
function. Follow findings to resolution.

Psychosis Psychotic reactions to disulfiram have been noted, usually attributable

to high disulfiram dosage associated with toxicity to other drugs (e.g.,
metronidazole, isoniazid) or the unmasking of underlying psychoses in
patients stressed by alcohol withdrawal. When psychosis is diagnosed
and other interacting drugs are present, reduce or discontinue
disulfiram and treat underlying psychoses as indicated.
*
Serious disulfiram-induced hepatic injury occurs rarely, and the precise etiology is
unknown.

Laboratory Testing in Disulfiram Therapy

Interval/Period Type of Test

Before starting disulfiram therapy to Breath or blood alcohol tests (if clinically indicated to
confirm abstinence and determine confirm abstinence)
baselines after stabilization Liver function tests: Alanine aminotransferase, aspartate
aminotransferase, gamma glutamyltransferase, alkaline
phosphatase, lactate dehydrogenase, bilirubin, total
protein, albumin, prothrombin time
Complete blood count, routine chemistries (if clinically
Interval/Period Type of Test

indicated)
Kidney function tests: Routine blood urea nitrogen
(BUN), creatinine
Pregnancy test (women of childbearing age)

10–14 days after initiation of therapy Liver function tests: Alanine aminotransferase, aspartate
and then monthly (or more frequently) aminotransferase, gamma glutamyltransferase, bilirubin
for first 6 months of therapy; every 3
months thereafter

Monthly during therapy Pregnancy test (women of childbearing age)

As clinically indicated during therapy Kidney function tests: BUN, creatinine

Urine toxicology screen: Perform only when concern
exists about unreported alcohol or drug use

Disulfiram overdose :
 High doses of disulfiram (up to 6 g daily) are relatively nontoxic in humans.
Symptoms of overdose include vomiting, headache, apathy, ataxia, motor
restlessness, irritability, hallucinations, psychosis, loss of consciousness and
convulsions. Death occurs by respiratory arrest, preceded by ascending
paralysis, and pathological lesions are seen in the liver, spleen, kidney and CNS,
with congestion in the adrenal gland and oedema in the heart muscle. Similar
lesions have arisen in animals following chronic administration.
 In overdosage situations, the stomach should be emptied promptly by induced
emesis or lavage. There is no specific therapy for acute overdosage with
Antabuse and general symptomatic and supportive measures should be
instituted and maintained for as long as necessary. (See Precautions, The
disulfiram-ethanol reaction.)

Treatment Duration and Discontinuing Disulfiram:

Prolonged disulfiram administration does not produce tolerance. Daily, uninterrupted dosing may
be continued until the patient has established stable, long-term alcohol abstinence. Depending on
the patient, disulfiram therapy may continue for months or years
For some patients who have completed successful treatment with disulfiram and who are facing
anticipated high-risk relapse situations such as social events or travel, it may be appropriate to
restart disulfiram along with behavioral interventions to help them cope with the high-risk
situation and avoid relapse.
No withdrawal syndrome is associated with discontinuing disulfiram, but patients must be
warned that disulfiram-alcohol reactions may occur within 2 weeks of discontinuing the
medication.
Confidentiality:
All of your records from this study will be treated as confidential medical records. The records
will be safeguarded according to the policy of the Lifespan institution. This policy is based on
Rhode Island law, which promotes protection of confidential health care information. State law
requires health care providers to report abuse or neglect of children to the Department of
Children, Youth and Families (DCYF). State law also requires health care providers to report
abuse or neglect of persons age 60 and older to the Department of Elderly Affairs.
While the results of the research study will probably be shared with other people and may be
published in scientific reports, your name and the fact that you were in the study will be kept
confidential.
In addition, we will obtain a federal certificate of confidentiality to ensure that your responses to
our questions are kept private.
Refusal/Withdrawal:
The decision whether undergo AAT is entirely up to you. Participation is voluntary. Also, if
you decide now to participate, you will be able to change your mind later and withdraw from the
study.
There will be no penalty or loss of health care benefits if you decide not to participate, or if you
withdraw from the AAT. If your doctor feels it is in your best interest, they may choose to end
your participation in this AAT at any time.
The treating doctor will provide you with additional information as it becomes available, that
may affect your decision to continue in the AAT.
Rights and Complaints:
If you have any complaints about your participation in this AAT, or would like more information
about the AAT/Disulfurm medicine or the rights of people who take part in in this AAT, you
may contact Dr.Mahesh Gowda,Telephone Number: 9845134915

I have reviewed this form with my provider and have had the chance to ask any questions. I
understand each of the statements written here and by signing give my consent for treatment of
my AAT.
.
I understand that I may withdraw this consent at any time, either verbally or in writing
except to the extent that action has been taken on reliance on it. This consent will last
while I am being treated for Alcohol dependence by the provider specified above unless
I withdraw my consent during treatment. This consent will expire 365 days after I
complete my treatment.
I understand that the records to be released may contain information pertaining to
psychiatric treatment and/or treatment for alcohol and/or drug dependence. These
records may also contain confidential information about communicable diseases
including HIV (AIDS) or related illness. I understand that these records are protected by
the Code of Federal Regulations Title 42 Part 2 (42 CFR Part 2) which prohibits the
recipient of these records from making any further disclosures to third parties without
the express written consent of the patient.
I acknowledge that I have been notified of my rights pertaining to the confidentiality of
my treatment information/records.
I acknowledge that i have read the above explanation of this study, that all of my questions have
been satisfactorily answered, and i agree to participate in this aat
I certify that i have explained fully to the above patient the nature and purpose, procedures and
the possible risk and potential benefits

_____________________ _________________________ __________

Patient Signature Patient Name (Print) Date
______________________ ___________________________ _________
Parent/Guardian Signature Parent/Guardian Name (Print) Date
______________________ ______________________________ _________
Witness Signature Witness Name (Print) Date

______________________ ______________________________ _________

Signature of Treating Doctor Treating Doctor Name (Print) Date

Signature of Treating Doctor Name of Treating DoctorDate

It is now far more difficult to arrange involuntary commitment for addiction treatment, but
it can happen if it is believed that the individual is an imminent danger to themselves or
other people.