Consumer medicine information

Serenace Tablets and Liquid

Haloperidol

BRAND INFORMATION

Brand name

Serenace Tablets and Liquid

Active ingredient

Haloperidol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Serenace Tablets and Liquid.

SUMMARY CMI

SERENACE [Tablets and Liquid]

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using SERENACE?

SERENACE contains the active ingredient haloperidol. SERENACE is used to treat mental illness including schizophrenia, mania, severe anxiety, behaviour problems in children with mental retardation, nausea and vomiting cause by cancer treatment, Tourette's syndrome and anxiety and pain during surgery.

For more information, see Section 1. Why am I using SERENACE? in the full CMI.

2. What should I know before I use SERENACE?

Do not use if you have ever had an allergic reaction to SERENACE or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use SERENACE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SERENACE and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SERENACE?

  • Tablets: Swallow SERENACE tablets with a glass of water.
  • Liquid: Shake the bottle well and accurately measure the dose with a medicine measure.
  • Take SERENACE at about the same time each day.

More instructions can be found in Section 4. How do I use SERENACE? in the full CMI.

5. What should I know while using SERENACE?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using SERENACE.
  • Tell your doctor if you notice any worm-like movements of the tongue, or other uncontrolled movements of the tongue, mouth, cheeks or jaw, which may progress to the arms and legs.
  • If you plan to have surgery that needs a general anesthetic, tell your doctor or dentist that you are taking SERENACE.
  • If SERENACE makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position.
  • If outdoors, wear protective clothing and use at least SPF 15+ sunscreen.
Things you should not do
  • Do not stop using this medicine suddenly or lower the dosage, even if you are feeling better, without checking with your doctor.
  • Do not take any medicines that cause drowsiness while you are takin SERENACE, unless recommended by your doctor.
Driving or using machines
  • Be careful driving or operating machinery until you know how SERENACE affects you.
  • It may cause dizziness, light-headedness, tiredness and drowsiness in some people. If this occurs, do NOT drive.
Drinking alcohol
  • Be careful when drinking alcohol while taking SERENACE.
  • It may make you more sleepy, dizzy or light-headed.
Looking after your medicine
  • Keep your tablets or liquid in their container until it is time to take them.
  • Keep your tablets or liquid in a cool dry place where the temperature stays below 30°C.

For more information, see Section 5. What should I know while using SERENACE? in the full CMI.

6. Are there any side effects?

Tell your doctor or pharmacist a soon as possible if you do not feel well while you are taking SERENACE. Some mild side effects include drowsiness, restlessness, agitation, anxiety, confusion, muscle weakness, nausea and vomiting. Some more serious side effects include skin rash, hives, extremely high body temperature, dizziness, unable to pass urine and breathing difficulties.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SERENACE [Tablets and Liquid]

Active ingredient(s): Haloperidol

Consumer Medicine Information (CMI)

This leaflet provides important information about using SERENACE. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SERENACE.

Where to find information in this leaflet:

1. Why am I using SERENACE?
2. What should I know before I use SERENACE?
3. What if I am taking other medicines?
4. How do I use SERENACE?
5. What should I know while using SERENACE?
6. Are there any side effects?
7. Product details

1. Why am I using SERENACE?

SERENACE contains the active ingredient haloperidol. SERENACE is an antipsychotic that works to correct chemical imbalances in the brain, which may cause mental illness. These chemicals may also effect the parts of the brain, which control nausea and vomiting.

SERENACE is used to treat:

  • Schizophrenia, an illness with disturbances in thinking, feelings and behaviour
  • Mania, an illness where the patient experiences episodes of overactivity, elation or irritability
  • Severe anxiety, tension or excitement and severe agitation, hyperactivity or aggression in patients with mental or emotional illness
  • Behavioural problems in children with mental retardation or mental illness
  • Nausea and vomiting (caused by cancer treatment)
  • Anxiety and pain during surgery (neurolept anaesthesia)
  • Tourette's Syndrome, a condition with uncontrolled vocal outbursts and body movements (tics).

Your doctor may have prescribed SERENACE for another reason.

2. What should I know before I use SERENACE?

Before you receive SERENACE, your doctor may recommend that you have an electrocardiogram or ECG.

Your doctor may also recommend that you have an ECG on a regular basis while taking SERENACE.

There is no evidence that this medicine is addictive or habit forming.

Warnings

Do not use SERENACE if:

  • You are allergic to haloperidol, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • You have or have had any of the following medical conditions:
    - Brain damage
    - Parkinson's Disease
    - Severe depression
    - Alcohol or drug intoxication
    - Spasticity, where a group of muscles are stiff and restricted in movement
    - Parkinsonian-like symptoms together with senility
    - Breast cancer
    - serious heart condition e.g. heart attack, heart failure, unusual heartbeat
  • You are taking medicines used to treat fast or irregular heartbeat (arrhythmia)
  • If the individual is unconscious or in a coma.
  • It is after the expiry date (EXP) printed on the pack.
  • If the packaging is torn or shows signs of tampering.

Symptoms of an allergic reaction to SERENACE may include shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, skin rash, itching or hives.

Check with your doctor if you:

Take any medicines for any other condition.

If you smoke as:

  • Nicotine can affect the amount of haloperidol in your body. Sudden change in your usual smoking habits can also change the effects of haloperidol.

Will be in a hot environment or do a lot of exercise as:

  • SERENACE may make you sweat less, causing your body to overheat.

Have any other medical conditions, especially:

  • Tumour of the pituitary gland, a small gland at the base of the brain
  • Brain tumour
  • Kidney problems
  • Difficulty passing urine
  • Heart and blood vessel problems
  • Fast or irregular heartbeats (arrhythmia)
  • Unusual amount of salt in the body
  • Liver disease
  • Disease of the blood with a reduced number of red or white blood cells or platelets
  • Prostate problems
  • Breast cancer or a family history of breast cancer
  • Breathing difficulties (asthma, emphysema, respiratory infections, silent pneumonia)
  • Paralytic ileus, a condition where the small bowel does not work properly
  • Blockage in your intestines
  • Epilepsy, seizures or fits
  • Diabetes
  • Low blood pressure
  • Sleep apnoea
  • An overactive or underactive thyroid gland
  • Glaucoma, a condition in which there is usually a build-up of fluid in the eye
  • Eye problems, such as diseases of the retina or blurred vision
  • Neuroleptic malignant syndrome, a reaction to some medicines with a sudden increase in body temperature, extremely high blood pressure and severe convulsions
  • Tardive dyskinesia, a reaction to some medicines with worm-like movements of the tongue, or other uncontrolled movements of the mouth, tongue, cheeks or jaws which may progress to the arms and legs
  • Phaeochromocytoma, a rare tumour of the adrenal gland which is near the kidneys
  • Subarachnoid haemorrhage, serious bleeding around the brain
  • Alcoholism or drug dependence
  • Dementia-related psychosis, loss of memory or mental ability.

The elderly with dementia-related psychosis and taking SERENACE may have a rare increased risk of death. Talk to your doctor if you have any questions.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Like most antipsychotic medicines, SERENACE is not recommended for use during pregnancy. However if you need to take SERENACE during your pregnancy, your doctor will discuss the risks and benefits involved in taking it.

Babies exposed to antipsychotic medicines including SERENACE during the third trimester of pregnancy are at risk of experiencing breathing problems, difficulty in feeding, spasms, restlessness, involuntary movements and/or withdrawal symptoms following delivery.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is no recommended for us while breast-feeding as it may pass into breast milk.

Use in Children

SERENACE is not recommended for use in children under the age of 3 years, as there is not enough information on its effects in this age group.

SERENACE should not be given to children under 12 years of age, unless directed by the child's doctor.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and SERENACE may interfere with each other. These include:

  • alcohol
  • nicotine or tobacco smoke
  • pain killers
  • benzodiazepines and other medicines used to treat anxiety or to help you sleep
  • medicines used to treat hayfever, coughs and colds
  • anticonvulsants, medicines used to control epilepsy
  • medicines used to control depression or mood swings e.g. fluoxetine, fluvoxamine, nefazodone, paroxetine, venlafaxine, lithium, carbamazepine
  • antipsychotic medicines, used to treat mental illnesses
  • medicines used to treat high blood pressure (hypertension) and heart conditions
  • medicines used to treat fast or irregular heartbeat (arrhythmia)
  • medicines used to treat Parkinson's Disease
  • anticholinergic medicines, used to prevent travel sickness, relieve stomach cramps or treat Parkinson's Disease
  • anticoagulants, medicines used to prevent blood clots e.g. warfarin
  • medicines used as appetite suppressants
  • tacrine, medicine used to treat dementia in Alzheimer's disease
  • stimulants such as amphetamine
  • adrenaline, a medicine used in emergency situations
  • rifampicin, antibiotic used to treat infections

The above medicines may either reduce the effectiveness of SERENACE, reduce its own effectiveness, and/or react with SERENACE resulting in untoward or sometimes dangerous side effects.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SERENACE.

4. How do I use SERENACE?

How much to take / use

  • Follow the instructions provided and use SERENACE until your doctor tells you to stop.
  • Your doctor or pharmacist will tell you how much SERENACE you will need to take each day. This depends on your condition and whether or not you are taking any other medicines.

Adults: 1 to 15 mg per day depending on severity, up to 100 mg per day.

Elderly: 1 to 3 mg per day is usually sufficient.

Children:

  • Initial dose: 1 to 3 mg per day.
  • Maintenance dose: 0.05 mg per kg of body weight daily.

When to take / use SERENACE

  • Take SERENACE at about the same time each day.
  • Take it at the same time each day will have the best effect. It will also help you remember when to take it.
  • It does not matter if you take SERENACE before or after food.

How to use

  • Tablets: Swallow SERENACE tablets with a glass of water.
  • Liquid: Shake the bottle well and accurately measure the dose with a medicine measure.
    Shaking the bottle and using a medicine measure will make sure that you get the correct dose. You can buy a medicine measure from your pharmacist.

How Long to Take It

  • Continue taking the tablets or liquid for as long as your doctor tells you.
  • SERENACE helps control your condition, but does not cure it. Therefore, it is important that you keep taking it every day.
  • Do not stop taking SERENACE unless your doctor tells you to, even if you feel better.

If you forget to use SERENACE

SERENACE should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember and then return to taking your medicine as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

This may increase the chance of you getting an unwanted side effect.

If you use too much SERENACE (overdose)

If you think that you have used too much SERENACE, you may need urgent medical attention.

Symptoms of an overdose to SERENACE include some of the side effects listed under Section 6. Are there any side effects?, but are usually of a more severe nature.If you are given too much SERENACE you may have coma, breathing difficulty, low or high blood pressure, drowsiness, muscle weakness or stiffness, unusual heartbeat, unusual or uncontrollable movements such as shaking and trembling.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using SERENACE?

Things you should do

Tell any other doctors, dentists, and pharmacists who are treating you that you are taking SERENACE.

If you are about to be started on any new medicine, remind your doctor, dentist or pharmacist that you are taking SERENACE.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking SERENACE.

Tell your doctor If you become pregnant while taking SERENACE.

If you need to have any medical tests while you are taking SERENACE, tell your doctor. It may affect the results of some tests.

Be sure to keep all of your doctor's appointments so that your progress can be checked. Your doctor will check your progress and may want to take some blood/eye/skin tests from time to time. This helps to prevent unwanted side effects.

Call your doctor straight away if you:

Notice any worm-like movements of the tongue, or other uncontrolled movements of the tongue, mouth, cheeks, or jaw, which may progress to the arms and legs.

  • These are symptoms of a condition called tardive dyskinesia, which may develop in people taking antipsychotic medicines, including SERENACE.
  • This condition is more likely to occur during long term treatment with this medicine, especially in elderly women. In very rare cases, this may be permanent. However, if detected early, these symptoms are usually reversible.

Remind any doctor, dentist or pharmacist you visit that you are using SERENACE.

Things you should not do

  • Do not give SERENACE to anyone else, even if their symptoms seem similar or they have the same condition as you.
  • Do not take SERENACE to treat any other complaints unless your doctor tells you to.
  • Do not stop taking SERENACE, or lower the dosage, even if you are feeling better, without checking with your doctor.
  • If you stop taking SERENACE suddenly, your condition may worsen or your chance of getting an unwanted side effect may increase. To prevent this, your doctor may gradually reduce the amount of SERENACE you take each day before stopping the medicine completely.
  • Do not take any medicines that cause drowsiness while you are taking SERENACE, unless recommended by your doctor.

Dizziness

  • If SERENACE makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position.
  • Getting up slowly may help. This will allow your body to get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Sun Sensitivity

  • If outdoors, wear protective clothing and use at least a SPF 15+ sunscreen. Do not use a sun lamp or tanning bed or booth.
  • SERENACE may cause your skin to be much more sensitive to sunlight than it is normally. Exposure to sunlight may cause a skin rash, itching, redness, or severe sunburn. If your skin does appear to be burning, tell your doctor immediately.
  • Make sure you keep cool in hot weather and keep warm in cool weather.
  • SERENACE may affect the way your body reacts to temperature changes.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SERENACE affects you.

As with other antipsychotic medicines, SERENACE may cause dizziness, light-headedness, tiredness, and drowsiness in some people.

Make sure you know how you react to SERENACE before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed.

If this occurs, do NOT drive.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while taking SERENACE.

Combining SERENACE and alcohol can make you more sleepy, dizzy or light-headed. Your doctor may suggest you avoid alcohol while you are taking SERENACE.

Looking after your medicine

  • Keep your tablets or liquid in their container until it is time to take them.
  • If you take the tablets or the liquid out of the container, they may not keep well.
  • Keep your tablets or liquid in a cool dry place where the temperature stays below 30°C

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Young children or adolescents and the elderly may have an increased chance of getting side effects.

Less serious side effects

Less serious side effectsWhat to do
  • drowsiness or tiredness
  • restlessness, agitation, anxiety or excitement
  • confusion
  • headaches
  • inability to sleep
  • muscle weakness
  • difficulty in speaking and/or swallowing
  • increased or decreased sweating
  • dry mouth
  • indigestion
  • nausea and/or vomiting
  • increased appetite
  • loss of appetite
  • weight changes
  • constipation
  • diarrhoea
  • increased salivation
  • blurred vision or difficulty focusing
  • changes in skin colour (pale skin)
  • hot, dry skin
  • swelling of your hands, feet and/or ankles
  • painful, swollen breasts or breast enlargement in men
  • unusual secretion of breast milk
  • changes in your menstrual periods
  • impaired sexual function in men
  • loss of blood sugar control, including in diabetes
Speak to your doctor if you have any of these less serious side effects and they worry you.
These are the more common side effects of SERENACE. They are usually mild and short-lived.

Serious side effects

Serious side effectsWhat to do
  • skin rash
  • pinkish, itchy swellings on the skin, also called hives or nettle rash
  • red, itchy spots which may blister or form raised, red, pale-centred marks
  • extremely high body temperature (fever)
  • symptoms of sunburn (such as redness, itching, swelling or blistering of the skin) which occur more quickly than normal
  • dizziness or spinning sensation (vertigo)
  • unable to pass urine
  • fast breathing
  • fast, pounding or irregular heart beats
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers
  • asthma and other breathing difficulties
  • bleeding or bruising more easily than normal
  • tiredness, headaches, being short of breath when exercising, dizziness and looking pale (anaemia)
  • yellowing of the skin and/or eyes
  • unusual movements, including trembling and shaking of the hands and fingers, twisting movements of the body, shuffling walk and stiffness of the arms and legs
  • sudden onset of uncontrollable muscle spasms affecting the eyes, head, neck and body
  • persistent painful erection (priapism)
  • seeing, feeling or hearing things that are not there (hallucinations)
  • worm-like movements of the tongue, or other uncontrolled movements of the tongue, mouth, cheeks, or jaw which may progress to the arms and legs
  • regular episodes of irregular heartbeat, dizziness and loss of consciousness.
If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:
  • sudden signs of allergy such as skin rash, itching or hives; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • severe spasms in the muscles of the shoulders, neck and upper body
  • convulsions, fits or seizures
  • sudden increase in body temperature, with sweating, fast heart beat, muscle stiffness and fluctuating blood pressure which may lead to coma (neuroleptic malignant syndrome)
  • very fast, uneven or forceful heartbeat (palpitations), weakness, fainting (symptoms relating to QT prolongation and Torsade de Pointes)
  • collapse
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

You may notice some side effects after you have finished taking SERENACE. The effects of SERENACE may last for days after you have stopped taking it.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SERENACE contains

Active ingredient
(main ingredient)		SERENACE tablets contain:
Haloperidol 0.5 mg, 1.5 mg and 5 mg
SERENACE Liquid contains:
Haloperidol 2 mg/mL
Other ingredients
(inactive ingredients)		SERENACE tablets contain:
  • lactose
  • starch – maize
  • acacia
  • magnesium stearate
  • calcium hydrogen phosphate
SERENACE 0.5 mg tablets also contain:
  • quinoline yellow CI47005
  • green s CI44090
SERENACE 5 mg tablets also contain:
  • brilliant scarlet 4R CI16255
SERENACE Liquid contains:
  • lactic acid
  • methyl hydroxybenzoate (preservative)
  • propyl hydroxybenzoate (preservative)
  • water
Potential allergensLactose

Do not take this medicine if you are allergic to any of these ingredients.

SERENACE products do not contain any sucrose, gluten, or tartrazine.

What SERENACE looks like

SERENACE Tablets: (oral)

0.5 mg tablet is green, scored, uncoated, plain on one side, in bottles of 100. (AUST R 10259).

1.5 mg tablet is white, scored, uncoated, plain on one side, in bottles of 100. (AUST R 10258).

5 mg tablet is red, scored, uncoated, plain on one side, in bottles of 50 and 100. (AUST R 10262).

SERENACE Liquid: (oral)

2 mg per mL liquid is a clear, colourless liquid in 100 mL bottles. (AUST R 10257).

Who distributes SERENACE

Aspen Pharmacare Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia

This leaflet was prepared in October 2022.

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Serenace Tablets and Liquid

Active ingredient

Haloperidol

Schedule

S4

 

1 Name of Medicine

Serenace tablets and liquid contain haloperidol.

2 Qualitative and Quantitative Composition

Serenace tablets contain either 0.5 mg, 1.5 mg, 5 mg or 20 mg haloperidol as the active ingredient. The tablets also contain lactose monohydrate, maize starch, acacia, magnesium stearate and calcium hydrogen phosphate dihydrate. In addition, Serenace 0.5 mg tablets contain quinoline yellow and green S, Serenace 5 mg tablets contain brilliant scarlet 4R and Serenace 20 mg tablets contain indigo carmine.
Serenace liquid contains 2 mg/mL haloperidol as the active ingredient. The liquid also contains lactic acid, purified water, with methyl hydroxybenzoate and propyl hydroxybenzoate as preservatives.

3 Pharmaceutical Form

Serenace tablets.

0.5 mg tablet: A round, green, compressed tablet plain on one side and scored on the other side.
1.5 mg tablet: A round, white compressed tablet, plain on one side and scored on the other side.
5 mg tablet: A round, red compressed tablet plain on one side and scored on the other side.
20 mg tablet: A light blue tablet, scored, uncoated, stamped "SEARLE" on one side. This tablet strength is currently not marketed.

Serenace oral liquid.

2 mg/mL liquid: A clear, colourless mobile liquid free from visible contamination. Available in 100 mL amber glass bottles with a white tamper evident child-resistant polypropylene cap.

4 Clinical Particulars

4.1 Therapeutic Indications

Chronic therapy.

The management of manifestations of psychotic disorders such as schizophrenia, psychosis due to organic brain damage or mental deficiency, the manic phase of manic depressive illness, Gilles de la Tourette syndrome.

Short-term therapy.

The treatment of acute alcoholism for the relief of delusions, hallucinations and confused states, and for the control of accompanying tremulousness and aggressive behaviour.
In the treatment of intractable nausea and vomiting associated with radiation or malignancy and not responding to other therapy. Neuroleptanalgesia.

4.2 Dose and Method of Administration

Warning.

Higher doses and intravenous administration of haloperidol appear to be associated with a higher risk of QT prolongation and Torsades de Pointes (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Where rapid control of an acutely disturbed patient is required, or where heavier than usual dosages are envisaged, or when parenteral administration, particularly repeated parenteral administration, is required, then the patient should be transferred as soon as possible to a situation where, ECG monitoring, parenteral antiparkinson medication and resuscitative measures are available. Appropriate precautions should be taken in patients with a history or evidence of cardiovascular disorders or epilepsy.
There is considerable variation from patient to patient in the amount of medication required for therapy. As with all antipsychotic drugs, it is important to titrate the dose of Serenace in accordance with the clinical effect and the severity of the disease. Monitoring of blood levels is not a routine procedure. Children and debilitated or geriatric patients may be more sensitive to Serenace, and the starting dose, maximum dose and maintenance doses are therefore generally lower for these patients. In all age groups, titration of dosage should be as rapid as possible, and when therapy is commenced with parenteral Serenace, a change to oral medication should be made as soon as possible.
Sedation should not be used as a control parameter, nor should Serenace be used to achieve sedation, since it may lead to gross overdose.
Once a satisfactory clinical response has been achieved by the titration method, the daily doses should be reduced to the lowest effective level.
No pharmacokinetic data are available to enable special recommendations to be given for patients with renal or hepatic impairment.
Also, no information on the effects of meals on drug absorption is available.

Oral administration.

Adults.

Moderate symptomatology.

1-5 mg per day.

Severe symptomatology.

5-15 mg per day. Daily oral dosages should be titrated against patient response and may be increased up to 20 mg. Once a satisfactory clinical response has been achieved by the titration method, the daily dose should be reduced to the lowest effective level.
Geriatric or debilitated patients. 1-3 mg per day is usually sufficient.
Children. For severely aggressive or hostile children or for the rare Gilles de la Tourette Syndrome, the initial dose should be 1-3 mg per day and Serenace liquid is recommended. Maintenance dose is usually 0.05 mg/kg body weight per day.
Oral total daily maintenance dose. Once continuous therapeutic control is achieved, there is a need to determine maintenance dosage. As pharmacokinetic studies to date have not addressed this problem, it is necessary to make an estimate by assuming plasma levels are to be maintained, that the plasma half-life of haloperidol is approximately 24 hours, and that the initial control is attained within 24 hours.
The maintenance dose may be calculated as half the total daily dose that is used to achieve control. This dose can then be given in divided doses morning and evening. To avoid excessive plasma levels, giving of the first maintenance dose should be delayed if possible until 4-8 hours after the last controlling dose.

4.3 Contraindications

Comatose states.
In the presence of central nervous system depression due to alcohol and other depressant drugs.
Severe depressive states.
Previous spastic diseases.
Senile patients with pre-existing parkinsonian symptoms.
Parkinson's disease.
Known hypersensitivity to haloperidol.
In patients with manifest occult lesions of the basal ganglia.
In patients with prolactin dependent tumours.
Serenace is also contraindicated in patients who are sensitive to haloperidol or other ingredients in the dosage form (see Section 6.1 List of Excipients).
In common with other neuroleptics, haloperidol has the potential to cause rare prolongation of the QT interval. Use of haloperidol is therefore contraindicated in patients with clinically significant cardiac disorders e.g. recent acute myocardial infarction, uncompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic medicinal products, QTc interval prolongation, history of ventricular arrhythmia or torsades de pointes, clinically significant bradycardia, second or third degree heart block and uncorrected hypokalaemia. Haloperidol should not be used concomitantly with other QT prolonging drugs (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Neuroleptic malignant syndrome (NMS).

A potentially fatal syndrome known as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of this syndrome are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and autonomic instability (irregular pulse or blood pressure). Additional signs may include elevated creatine phosphokinase (CPK), myoglobinuria and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated.
The management of NMS should include immediate discontinuation of antipsychotic drugs, intensive symptomatic treatment and monitoring, and treatment of any serious medical problems for which specific treatments are available. Dantrolene and bromocriptine have been used for the treatment of NMS. The reintroduction of antipsychotic therapy after recovery from NMS should be carefully considered since recurrences of NMS have been reported. Haloperidol should be used cautiously in patients exposed to high temperatures. Hyperpyrexia and heat stroke have been reported to be associated with haloperidol, not associated with other manifestations of NMS (see Section 4.8 Adverse Effects (Undesirable Effects)).

Tardive dyskinesia.

A syndrome consisting of potentially irreversible, involuntary dyskinetic movements may develop in patients treated with antipsychotic drugs (see Section 4.8 Adverse Effects (Undesirable Effects)). Although the dyskinetic syndrome may remit partially or completely if the medication is withdrawn, it is irreversible in some patients. The prevalence of this syndrome appears to be highest among the elderly, particularly elderly women.
At the present time, it is uncertain whether neuroleptic drugs differ in their potential to cause tardive dyskinesia. Since there is a significant prevalence of this syndrome associated with the use of neuroleptic drugs, and since there is no known effective treatment, chronic use of these drugs should generally be restricted to patients for whom there is no alternative therapy available with better risk acceptability. The risk of developing irreversible tardive dyskinesias increases the duration of treatment and total cumulative doses, although in some instances, tardive dyskinesia may develop after relatively short periods of treatment at low doses.
The risk of developing tardive dyskinesia may, therefore, be minimised by reducing the dose of the neuroleptic drug used and its duration of administration, consistent with the effective management of the patient's condition. There is no known effective treatment. If manifestations of tardive dyskinesia are noted, the neuroleptic drug should be discontinued.

QT prolongation and Torsades de Pointes.

Higher doses and intravenous administration of haloperidol appear to be associated with a higher risk of QT prolongation and Torsades de Pointes. Rare cases of sudden death have been reported even in the absence of predisposing factors. It is advisable to be particular cautious in treating patients using haloperidol who:
have other QT prolonging conditions, including electrolyte imbalance (particularly hypokalaemia, hypocalcaemia or hypomagnesaemia),
have underlying cardiac abnormalities, hypothyroidism, familial long QT syndrome, or patients with risk factors for ventricular arrhythmias, such as cardiac disease, subarachnoid haemorrhage, starvation and alcohol abuse,
are taking drugs which are known to prolong the QT interval (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Because of this risk of Torsades de Pointes and QT prolongation, a baseline ECG is recommended before haloperidol is given. If repeated doses are given, continuous ECG monitoring is also recommended.

Alcoholism, active.

CNS depression may be potentiated and risk of stroke may be increased. Increased hypotensive effects and the potential for alcohol intoxication may also occur.

Severe cardiovascular diseases.

Haloperidol in therapeutic doses does not usually affect blood pressure significantly but care should be exercised in patients with severe cardiovascular disorders or being treated with antihypertensive drugs because of the possibility of unexpected hypotension, and/or precipitation of angina. Severe or prolonged hypotension may require vasopressors. Adrenaline should not be used since haloperidol may block its vasopressor activity and cause further decrease in blood pressure. Therefore, noradrenaline or metaraminol should be used instead.
Anginal pain may be provoked in patients with ischaemic heart disease.
Caution should be observed in patients with arteriosclerosis who may have occult lesions of the basal ganglia (see Section 4.3 Contraindications).

Epilepsy.

Haloperidol may be given to epileptics but adequate anticonvulsant therapy should be maintained as haloperidol may decrease the seizure threshold. It has been reported that haloperidol can trigger seizures in known epileptics that were previously controlled. Caution is, therefore, advised in patients receiving anticonvulsants, with a history of seizures, or with EEG abnormalities and in conditions predisposing to convulsions (e.g. alcohol withdrawal and brain damage).

Glaucoma.

Glaucoma or a predisposition to glaucoma may be triggered because of the secondary anticholinergic effects of haloperidol.

Sleep apnoea.

Sleep apnoea and related disorders have been reported in patients treated with antipsychotic medicines, with or without prior history of sleep apnoea, and with or without concomitant weight-gain. In patients who have a history of or are at risk for sleep apnoea, or who are concomitantly using central nervous system depressants, haloperidol should be used with caution.

Use in hepatic function.

Impairment of hepatic function may alter metabolism of haloperidol.

Hyperthyroidism or thyrotoxicosis.

Severe neurotoxicity such as rigidity and inability to walk or talk may result when these patients are treated with antipsychotics. Thyrotoxic patients may be more prone to develop extrapyramidal symptoms. Antipsychotic treatment in these patients should always be accompanied by appropriate monitoring and therapy.

Pulmonary insufficiency.

A number of cases of bronchopneumonia, sometimes fatal, have been reported following the use of antipsychotic drugs. Haloperidol should be used with caution in patients with pulmonary insufficiency, such as asthma, emphysema or acute pulmonary infections. Haloperidol may cause potentiation of breathing impairment and may possibly lead to 'silent pneumonia'.

Use in renal impairment.

Renal function impairment is mostly a concern at higher dosage since renal clearance of unchanged drug is relatively low.

Urinary retention.

Urinary retention may be potentiated due to secondary anticholinergic effects.

Use in the elderly.

Elderly or debilitated patients receiving haloperidol should be observed for evidence of oversedation which, unless alleviated, could result in complications such as terminal stasis pneumonia.
Elderly patients tend to develop higher plasma concentrations of haloperidol because of changes in distribution due to decreases in lean body mass, total body water, and albumin, and often an increase in total body fat composition. These patients usually require lower initial dosage and a more gradual titration of dose (see Section 4.2 Dose and Method of Administration). Elderly patients exhibit an increased sensitivity to the anticholinergic, sedative and extrapyramidal side effects of haloperidol. Careful observation during haloperidol therapy for early signs of tardive dyskinesia and reduction of dosage or discontinuation of medication may prevent a more severe manifestation of the syndrome.

Sudden death in elderly patients with dementia.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Paediatric use.

As the safety and effectiveness of haloperidol has not been generally established in children, the drug is not recommended for use in the paediatric age group except in severely aggressive and hostile children or for the treatment of the rare Gilles de la Tourette syndrome. Haloperidol should not be used in children under 3 years of age. Children are highly susceptible to the extrapyramidal side effects of haloperidol, especially dystonias.

Bipolar mood disorders.

When haloperidol is used to control mania in cyclic disorders, a rapid mood swing to depression may occur. As with all antipsychotic agents, haloperidol should not be used alone where depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis coexist. However, it should be noted that haloperidol may impair the metabolism of tricyclic antidepressants (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Dental.

Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss and toothpicks as the leukopenic and thrombocytopenic effects of haloperidol may result in an increased incidence of microbial infection, delayed healing and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts have returned to normal. The peripheral anticholinergic effects of haloperidol may decrease or inhibit salivary flow, especially in middle aged or elderly patients, thus contributing to the development of caries, periodontal disease, oral candidiasis and discomfort.

Other precautions.

It should be borne in mind that the antiemetic action of haloperidol may relieve nausea and vomiting, and so obscure the diagnosis of an underlying organic disorder which was causing these symptoms.
Ocular or cutaneous changes and decreases in serum cholesterol have occurred following administration of a butyrophenone structurally related to haloperidol. In the same study which reported these changes, haloperidol was shown to be free of these side effects. However, it is advisable to carefully observe patients who receive haloperidol for a prolonged period in order to identify any changes in the skin or eyes.
Haloperidol should be used with caution in patients with known allergies or with a history of allergic reactions to drugs.
Caution is advised in patients receiving anticoagulants since an isolated instance of interference occurred with the effects of one anticoagulant (phenindione).
If concomitant antiparkinson medication is required, it may have to be continued after haloperidol is discontinued, because of the different excretion rates, extrapyramidal symptoms may occur if both haloperidol and the antiparkinson agent are discontinued simultaneously. The physician should keep in mind the possible anticholinergic effects associated with antiparkinson agents.
Caution is advised in patients with phaeochromocytoma.
In schizophrenia, the response to antipsychotic drug treatment may be delayed. If drugs are withdrawn, recurrence of symptoms may not become apparent for several weeks or months.
With parenteral haloperidol in the acute situation, the use of a prophylactic anticholinergic agent (e.g. benztropine) is recommended to cover the period of parenteral administration and for several days afterwards.
There is considerable variation from patient to patient in the amount of medication required for therapy. Close observation is required during dosage titration in order to minimise the risk of overdosage or emergence of psychotic manifestations prior to the next dose. This is particularly important in patients with impaired liver or renal function.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacokinetic interactions.

There is evidence to suggest that haloperidol is a substrate of CYP3A4 and CYP2D6, and inhibitor, as well as a stimulator of CYP2D6. Studies also suggested that reduced haloperidol, one of the metabolites of haloperidol, is a substrate of CYP3A4 and an inhibitor of CYP2D6. Involvement of these isoforms in the biotransformation of haloperidol may explain some of the drug interactions observed.
Haloperidol inhibits the metabolism of tricyclic antidepressants, increasing the blood levels of these drugs. This may result in increased tricyclic antidepressant toxicity as well as increased anticholinergic effects. It is thought that inhibition of CYP2D6 by haloperidol or reduced haloperidol is responsible for this inhibitory effect. On the other hand, it is not known whether the metabolism of haloperidol is affected when tricyclic antidepressants is coadministered.
In pharmacokinetic studies, mild to moderately increased haloperidol levels have been reported when haloperidol was given concomitantly with quinidine, buspirone or fluoxetine. It may be necessary to reduce the dosage of haloperidol when any of these drugs are used concomitantly with haloperidol. The exact mechanism responsible for the interactions is not known but may be secondary to inhibition of CYP2D6 by quinidine, competition with CYP3A4 by buspirone and inhibition of CYP2D6 and CYP3A4 by fluoxetine. It is not known whether haloperidol affects the levels of quinidine or buspirone whereas fluoxetine levels appear to be unaffected when used concomitantly with haloperidol. Antidepressants such as fluvoxamine, nefazodone, paroxetine and venlafaxine may increase haloperidol concentrations by possibly inhibiting CYP2D6 mediated metabolism of haloperidol similarly to that seen with fluoxetine.
Due to competitive inhibition of CYP2D6 mediated haloperidol metabolism and increased dopamine2 blockade, coadministration of haloperidol and olanzapine may result in an increased risk of Parkinsonism.
A significant fall in haloperidol plasma levels occurs when prolonged treatment with enzyme inducing drugs such as carbamazepine, phenobarbitone, phenytoin or rifampicin is added to haloperidol therapy. This is thought to be the result of the ability of these drugs to induce CYP3A4, thereby accelerating the metabolism of haloperidol; serum concentrations of haloperidol may be significantly reduced. Therefore, during therapy with this combination, the dosage of haloperidol may need to be increased. Conversely, after stopping therapy with such drugs, it may be necessary to reduce the dosage of haloperidol. Haloperidol does not appear to influence the pharmacokinetics of carbamazepine and phenobarbitone. Whether or not haloperidol affects the plasma level of rifampicin is at present unclear.
The clearance of haloperidol is greater in tobacco smokers as compared with nonsmokers, and serum concentrations of haloperidol are lower in smoking patients. It is suggested that plasma concentrations of haloperidol be monitored in patients who either start or stop smoking.

Pharmacodynamic interactions.

Haloperidol may block the vasopressor activity of adrenaline and related sympathomimetic agents and cause a paradoxical further lowering of blood pressure in hypotensive patients. Haloperidol may also reverse the blood pressure lowering effects of adrenergic blocking agents such as guanethidine. Concomitant use of propranolol and haloperidol therapy has been reported to result in hypotension and cardiopulmonary arrest. This is due to alpha-receptor binding and intrinsic relaxant effects on peripheral blood vessels by haloperidol and relaxant effects on peripheral vessels by propranolol.
Drugs known to prolong the QT interval may affect haloperidol therapy (see Section 4.4 Special Warnings and Precautions for Use, QT prolongation and Torsades de Pointes). Concurrent use of haloperidol with antiarrhythmic agents may result in additive cardiac effects (see Section 4.4 Special Warnings and Precautions for Use, QT prolongation and Torsades de Pointes).
High doses of haloperidol may potentiate the action of methyldopa. This combination has reportedly resulted in dementia and enhanced CNS effects (e.g. disorientation, memory loss, slowed or difficult thought, aggression, irritability and mental retardation) in several patients.
Haloperidol blocks dopamine receptors. Haloperidol may therefore interfere with the antiparkinsonian effects of levodopa. Cabergoline, a long acting dopamine2 receptor agonist, should not be used concurrently with haloperidol, a dopamine2 antagonist, due to the antagonistic pharmacologic effects and therefore, decreased therapeutic effect of both drugs.
Parkinsonian syndrome has been reported with concomitant use of tacrine and haloperidol due to increased acetylcholine activity in striatal region of the brain.
Alcohol may potentiate the sedative effect of haloperidol, thereby impairing the ability of patients to perform activities requiring mental alertness. Concurrent use of alcohol and haloperidol may cause hypotension and increase alcohol intoxication (see Section 4.4 Special Warnings and Precautions for Use).
Haloperidol will potentiate the action of other central nervous system depressants (e.g. anaesthetics, opiates, barbiturates and alcohol).
The combination of lithium with an antipsychotic agent such as haloperidol, has occasionally produced an acute encephalopathic syndrome characterised by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leucocytosis, elevated serum enzymes and serum urea and followed by irreversible brain damage. Although a casual relationship has not been established, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity, and treatment discontinued should such signs appear.
Dextromethorphan is metabolised by CYP2D6. Concomitant use of dextromethorphan and haloperidol, an inhibitor of this isoenzyme, may result in elevated concentrations of dextromethorphan and increased adverse effects (CNS excitement, mental confusion, respiratory depression, nervousness, tremors, insomnia, and diarrhoea). A reduction of dextromethorphan doses may reduce or resolve adverse effects.
Haloperidol has been reported to antagonise the anticoagulant activity of phenindione and coumarin anticoagulants.
Increases in intraocular pressure may occur in patients receiving anticholinergic agents, including anti-Parkinsonian agents, concurrently with haloperidol.
Concurrent use of amphetamines and haloperidol may decrease both the stimulant effects of amphetamines as well as the antipsychotic effects of haloperidol.
The anticholinergic effects of other drugs may be intensified when used concurrently with haloperidol e.g. anticholinergic agents, antihistamines, tricyclic antidepressants, MAO inhibitors and antidyskinetic agents.
Concurrent use of anticonvulsants with haloperidol may cause a change in the pattern and/or frequency of seizures; dosage adjustments of anticonvulsants may be necessary. Tramadol may increase the seizure risk in patients taking other medications that lower the seizure threshold, such as haloperidol.
Haloperidol may interfere with the effects of bromocriptine; concurrent use may increase serum prolactin levels and dosage adjustment of bromocriptine may be necessary.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The animal data falls into three broad areas: female fertility, male fertility and effects in offspring.
There are no human data on the effects of haloperidol on male or female fertility. In female rats, administration of haloperidol induced oestrus cycle disruptions. In female mice, delays in the implantation, cleavages, and blastocele formation followed subcutaneous administration of haloperidol prior to ovulation. In male rats, oral administration of haloperidol prior to mating reduced fertility, increased pre-implantation loss, and induced histopathological changes in the reproductive organs. Following intraperitoneal administration of haloperidol to female rats from early pregnancy to weaning, the frequency of ejaculation in offspring was reduced.
Various dose levels were used in the above animal studies and in some studies a no effect level was not established. The relationship between the effects at the given dose levels in mice and rats and potential toxicity in humans is unknown.
(Category C)
The Australian categorisation definition of Category C: "Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details."
When given in high doses during late pregnancy, butyrophenones may cause prolonged neurological disturbances in the newborn infant. In pregnant mice, rats and hamsters, administration of haloperidol during the period of organogenesis has produced a range of adverse effects, including embryolethality, gross malformations such as cleft palate and neuronal tube defects, and reduced brain and body weight and behavioural effects in offspring. The significance of these findings for human exposure to therapeutic doses of haloperidol is unknown.

Nonteratogenic class effect.

Neonates exposed to antipsychotic drugs (including haloperidol) during the third trimester of pregnancy are at risk of experiencing extrapyramidal neurological disturbances and/or withdrawal symptoms following delivery. There have been postmarket reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self limited, in other cases neonates required additional medical treatment or monitoring.
Haloperidol should be used during pregnancy only if the anticipated benefit outweighs the risk. The administered dose and duration of treatment should be as low, and as short as possible.
 Haloperidol is distributed into breast milk. Safe use of haloperidol by nursing mothers has not been established; therefore, its use is not recommended. The frequency of ejaculation in offspring was reduced following intraperitoneal administration of haloperidol to female rats from early pregnancy to weaning (see Effects on fertility).

4.7 Effects on Ability to Drive and Use Machines

Haloperidol may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be warned accordingly.

4.8 Adverse Effects (Undesirable Effects)

In the low dosage range (1-2 mg daily), adverse effects from haloperidol have been infrequent, mild and transitory. In patients receiving higher doses, some adverse effects are seen more frequently. Neurological effects are the most common. See Table 1.

Akathisia.

May appear within the first 6 hours after dose; often indistinguishable from psychotic agitation. Akathisia is best managed by a reduction in dosage in conjunction with the temporary use of an oral antiparkinson drug.

Dystonias.

Appear most often in children and young adults and early in treatment; may subside within 24 to 48 hours after discontinuation of haloperidol. Dystonias, which can produce laryngeal spasm or bronchospasm, may be controlled by intravenous or intramuscular administration of benztropine mesylate (1-2 mg IM or IV) or biperiden (2-10 mg IM or IV), or intravenous diazepam (10 mg IV). A pseudo Parkinson rigidity syndrome may occur later during the course of treatment and may respond to antiparkinson agents.

Parkinsonian effects.

Are characterised by difficulty in speaking or swallowing; loss of balance control; mask-like face; shuffling gait; stiffness of arms or legs; trembling and shaking of hands and fingers. Parkinsonian effects are more frequent in the elderly; symptoms may be seen in the first few days of treatment or after prolonged treatment, and can recur after even a single dose. They sometimes remit spontaneously as treatment continues, or can be relieved by a reduction in dose or the temporary use of antiparkinson medication.
It has been reported that some extrapyramidal reactions may persist even after a reduction in dosage and/or treatment with antiparkinson drugs. In such cases, the drug should be discontinued.

Tardive dyskinesia.

(Lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements; uncontrolled movements of the arms and legs) is more frequent in elderly patients, women, and patients with brain damage. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of the drug increases. Less commonly, the syndrome can develop after relatively brief treatment periods at low doses. It may persist after discontinuation of haloperidol.
The syndrome may become clinically recognisable either during treatment, upon dosage reduction or upon withdrawal of treatment. The dosage of antipsychotic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder, since the syndrome may be masked by a higher dose. In patients requiring long-term treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be prescribed. The need for continued treatment should be reassessed periodically.
There is no known effective treatment for tardive dyskinesia. Antiparkinson agents usually do not alleviate the symptoms. It is suggested that antipsychotic agents be discontinued if symptoms of tardive dyskinesia appear.

Neuroleptic malignant syndrome (NMS).

Characterised by difficult or unusually fast breathing; fast heartbeat or irregular pulse; high fever; high or low blood pressure; increased sweating; loss of bladder control; severe muscle stiffness; seizures; unusual tiredness or weakness; unusually pale skin. Additional signs may include elevated creatinine phosphokinase, rhabdomyolysis and acute renal failure. May occur at any time during neuroleptic therapy, but is most commonly seen after start of therapy or after patient has switched from one neuroleptic to another, during combination therapy with other psychotropic medication, or after a dosage increase.
The management of neuroleptic malignant syndrome should include immediate discontinuation of antipsychotic drugs, intensive monitoring and treatment of symptoms, and treatment of any associated medical problems (e.g. pneumonia, systemic infection).

Tardive dystonia.

Increased blinking or spasm of eyelid; unusual facial expressions or body positions; uncontrolled twisting movements of neck, trunk, arms, or legs.

Other central nervous system effects.

Drowsiness, depression, anxiety, euphoria, lethargy, agitation, insomnia, headache, confusion, sedation, anorexia, vertigo, restlessness, apprehension, grand mal seizures. Toxic psychosis may occur with overdose.

Cardiovascular effects.

Orthostatic hypotension, tachycardia, increased respiratory rate, QT prolongation, ventricular arrhythmias, polymorphous configuration of torsade de pointes.

Haematological effects.

Agranulocytosis (sore throat and fever, unusual bleeding or bruising), mild and usually transient leukopenia and leucocytosis, minor decreases in red blood cell counts, anaemia, tendency toward lymphocytosis and monocytosis.

Hepatobiliary effects.

Impaired liver function and/or jaundice or cholestatic hepatitis (no causal relationship has been established).

Respiratory effects.

Laryngospasm, bronchospasm, increased depth of respiration, bronchopneumonia sometimes fatal.

Dermatological and hypersensitivity reactions.

Hypersensitivity reactions, local reactions as erythema, swelling or tender lumps, maculopapular and acneiform skin reactions and isolated cases of photosensitivity and loss of hair, urticaria, exfoliative dermatitis and erythema multiforme.

Endocrine effects.

Hyperprolactinaemia, gynaecomastia, menstrual irregularities including oligo or amenorrhoea, mastalgia, breast engorgement, impotence or increased libido, lactation, hyperglycaemia, hypoglycaemia, hyponatraemia, inappropriate antidiuretic hormone secretion (very rare).

Gastrointestinal effects.

Constipation, anorexia, nausea, vomiting, diarrhoea, dyspepsia, heartburn, hypersalivation.

Autonomic effects.

Blurred vision, dryness of mouth, urinary retention, excessive perspiration or salivation, priapism and erectile dysfunction.

Ocular effects.

Cataract, retinopathy, visual disturbances.

Other effects.

Heat stroke (hot, dry skin, inability to sweat, muscle weakness, confusion), increased sensitivity of skin to sun, weight gain, peripheral oedema.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms and findings would be an exaggeration of the known pharmacological effects and adverse reactions. The most prominent symptoms would be:
1. Severe extrapyramidal reactions;
2. Hypotension;
3. Sedation.
Sometimes coma with respiratory depression and hypotension, which could be severe enough to produce a shock-like state, can occur. Extrapyramidal reactions may consist of muscular weakness or rigidity and a generalised or localised tremor. Hypertension, rather than hypotension, is also possible. Convulsions, QT prolongation and ventricular arrhythmias including torsade de pointes may occur.

Treatment of overdose.

There is no specific antidote. Treatment is largely symptomatic and supportive. Activated charcoal may be administered to decrease drug absorption.

Note.

Dialysis is not effective in removing excessive systemic haloperidol.
For comatose patients, establish a patent airway by use of an oropharyngeal airway or endotracheal tube. Respiratory depression may necessitate artificial respiration.
Convulsions may be treated with IV diazepam, however, respiratory status should be monitored during its administration.
Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma or concentrated albumin and vasopressor agents such as dopamine or noradrenaline.
Adrenaline should not be used, since haloperidol may reverse its action and cause profound hypotension.
In cases of severe extrapyramidal reactions, antiparkinson medication (e.g. benztropine mesylate 1-2 mg IM or IV) should be administered parenterally.
ECG and vital signs should be monitored. Hypothermia should be managed with external warming.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Although the complex mechanism of the therapeutic effect of haloperidol is not clearly established, it is known that it produces a selective effect on the central nervous system by competitive blockade of postsynaptic dopamine (D2) receptors in the mesolimbic dopaminergic system, and an increased turnover of brain dopamine to produce its tranquillising effects. With subchronic therapy, depolarisation blockade, or diminished firing rate of the dopamine neurone (decreased release) along with D2 postsynaptic blockade results in the antipsychotic action.
Blockade of dopamine receptors in the nigrostriatal dopamine pathway produces extrapyramidal motor reactions; blockade of dopamine receptors in the tuberoinfundibular system decreases growth hormone release and increases prolactin release by the pituitary. There is also some blockade of alpha-adrenergic receptors of the autonomic system.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Haloperidol is rapidly absorbed from the gastrointestinal tract following oral administration but appears to undergo first-pass metabolism in the liver. Peak plasma levels of haloperidol occur within two to six hours of oral dosing and about twenty minutes after intramuscular administration.

Distribution.

Haloperidol is approximately 92% bound to plasma proteins. The distribution of haloperidol into the human body tissues and fluids has not been fully determined. In animal studies, the drug is mainly distributed into the liver, with lower concentrations being distributed into the brain, lungs, kidneys, spleen and heart. Haloperidol is also distributed into breast milk.

Metabolism.

Metabolism of haloperidol occurs in the liver. Haloperidol is metabolised by oxidative N-dealkylation of the piperidine nitrogen to form flurophenylcarbonic acids and piperidine metabolites which appeared to be inactive, and by reduction of the butyrophenone carbonyl to the carbinol, forming the alcohol hydroxyhaloperidol. Limited data suggest that reduced metabolite, hydroxyhaloperidol, has some pharmacological activity, although its activity appears to be less than that of haloperidol. There is evidence of enterohepatic recycling and due to the influence of the first-pass effect of metabolism in the liver, plasma concentrations following oral administration are lower than those following intramuscular administration. Haloperidol and its metabolites are excreted in the urine, via the bile and in the faeces. The plasma half-life of haloperidol after oral administration ranges from 12 to 38 hours. Studies have shown that CYP3A4 and/or CYP2D6 are involved in the metabolic biotransformation of haloperidol.

Excretion.

The mean plasma half-life (terminal elimination) has been determined as 20.7 ± 4.6 (SD) hours, and although excretion begins rapidly, only 24 to 60% of ingested radioactive drug is excreted (mainly as metabolites in urine; some in faeces) by the end of the first week, and very small but detectable levels of radioactivity persist in the blood and are excreted for several weeks after dosing. In humans, haloperidol glucuronide is a major metabolite excreted in the urine. About 1% of the ingested dose is recovered unchanged in the urine. The slow excretion may be related to a high degree of plasma protein binding. Haloperidol is highly lipid soluble and may remain in fatty tissue for some weeks.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

There was no evidence of carcinogenicity in Wistar rats following oral administration of haloperidol for 24 months at doses up to 5 mg/kg/day (about fivefolds the maximum recommended human dose based on body surface area). In female mice, there was a statistically significant increase in mammary gland neoplasia and total tumour incidence following oral administration of haloperidol at doses of 1.25 and 5 mg/kg/day (less than, and about twice, the maximum recommended human dose based on body surface area), and a statistically significant increase in pituitary gland neoplasia at 5 mg/kg/day. In male mice, there were no carcinogenic effects. Haloperidol increases prolactin levels, which may affect human breast cancers, one-third of which are prolactin dependent in vitro. Although clinical studies have not shown a clear association between chronic administration of antipsychotic drugs (including haloperidol) and an increase in the incidence of breast cancers, it may be a factor of importance when prescribing haloperidol for patients in which breast cancer was previously detected.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

Tablets: 2 years.
Oral liquid: 3 years.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Serenace tablets.

Serenace tablets contain either 0.5, 1.5, 5 or 20 mg of haloperidol. The tablets are supplied in white HDPE bottles with white child-resistant polypropylene caps.

0.5 mg tablet.

A round, green, compressed tablet plain on one side and scored on the other side. Bottles of 100 and 500 tablets.

1.5 mg tablet.

A round, white compressed tablet, plain on one side and scored on the other side. Bottles of 100 and 1000 tablets.

5 mg tablet.

A round, red compressed tablet plain on one side and scored on the other side. Bottles of 50, 100 and 500 tablets.

20 mg tablet.

A light blue tablet, scored, uncoated, stamped "SEARLE" on one side, in bottles of 100 and 500. This tablet strength is currently not marketed.

Serenace oral liquid.

2 mg/mL liquid.

A clear, colourless mobile liquid free from visible contamination. Available in 15 mL, 100 mL and 500 mL amber glass bottles with a white tamper evident child-resistant polypropylene cap.
(Note: Not all presentations may be marketed).

6.6 Special Precautions for Disposal

In Australia, an unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Haloperidol is a psychotropic drug of the butyrophenone series and is not related chemically to phenothiazines. Haloperidol is chemically described as 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1 -butanone. Its molecular formula is C21H23ClFNO2 and the molecular weight is 375.90.
Haloperidol presents as an odourless, tasteless, white to faintly yellowish amorphous or microcrystalline powder. It is insoluble in water but sparingly soluble in alcohol. Solutions are affected by light and can become discoloured after a few hours exposure; the discolouration is prevented by storage in brown glass containers.

CAS number.

Haloperidol (CAS- 52-86-8) has the following chemical structure:

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes