Consumer medicine information

Haldol Decanoate

Haloperidol decanoate

BRAND INFORMATION

Brand name

Haldol Decanoate

Active ingredient

Haloperidol decanoate

Schedule

What is in this leaflet

This leaflet answers some common questions about Haldol injection. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of treating you with Haldol against the benefits this medicine is expected to have for you.

If you have any concerns about being treated with Haldol, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What Haldol is used for

Haldol contains the active substance haloperidol (as haloperidol decanoate). This belongs to a group of medicines called ‘antipsychotics’.

Haldol is a long-acting antipsychotic. It works by correcting the chemical imbalances in the brain, which may cause mental illness.

Haldol is used in adults whose condition has previously been treated with haloperidol taken by mouth. It is used for illnesses affecting the way you think, feel or behave. These include mental health problems (such as schizophrenia).

These illnesses may make you:

Feel confused (delirium)
See, hear, feel or smell things that are not there (hallucinations)
Believe things that are not true (delusions)
Feel unusually suspicious (paranoia)
Feel very excited, agitated, enthusiastic, impulsive or hyperactive
Feel very aggressive, hostile or violent.

Your doctor may have prescribed Haldol for another use.

Ask your doctor or healthcare professional if you have any questions about why this medicine has been prescribed for you.

Haldol is not addictive.

Before you are given Haldol

When you must not be given it:

Do not give Haldol to anyone who is unconscious or in a coma.

You must not be given Haldol if you:

have severe drowsiness and slowness due to illness or the use of alcohol or medicine
feel unusually confused, dizzy or sleepy
suffer from severe depression
have or have ever had muscle stiffness, restricted or uncontrollable movement due to certain medical conditions, such as Parkinson's disease
have a type of dementia called 'Lewy body dementia'
have progressive supranuclear palsy (PSP).
have an allergy to Haldol or any of the ingredients. See Product Description at the end of this leaflet for a list of ingredients.
Signs of allergy may include skin rash, itching, shortness of breath, and/or swollen face that may lead to difficulty breathing or swallowing.
If you think you are having an allergic reaction, tell your doctor immediately or go to the Accident and Emergency department at the nearest hospital.

Do not give Haldol if the packaging is torn or shows signs of tampering and if it is beyond the expiry date (month and year) printed on the pack.

Before you are given it:

You must tell your doctor if you:

are pregnant or planning to become pregnant.
Like most antipsychotic medicines, Haldol is not recommended for use during pregnancy. Discuss with your doctor the risks and benefits involved in using it.
are breast feeding or wish to breastfeed.
Small amounts of the medicine may pass into the mother's milk and on to the baby. Discuss with your doctor the risks and benefits involved in using it.
suffer from loss of contact with reality and inability to think and judge clearly, or from a general decline mental ability (e.g. dementia related psychosis)
have ever had bleeding in the brain, or your doctor has told you that you are more likely than other people to have a stroke
have or have ever had a heart problem or a family history of heart problems, such as an unusual heart beat or a fast heartbeat, or are taking a heart medication
have or have ever had low blood pressure
have or have ever had a rare heart disorder known as QT-prolongation which sometimes runs in families
have or have ever had uncontrolled movements of the tongue, mouth, cheeks or jaws which may progress to the arms and legs (also known as tardive dyskinesia)
have or have ever had a sudden increase in body temperature, extremely high blood pressure and severe convulsions (also known as neuroleptic malignant syndrome)
have or have ever had epileptic fits or convulsions (seizures)
have depression
have or have ever had kidney or liver disease
have a very active thyroid gland (hyperthyroidism)
have had blood clots, or a family history of blood clots. Blood clots in the lungs and legs have been seen in patients taking antipsychotic medicines
experience a significant increase in weight while taking other antipsychotic medications. Clinically significant weight gain has also been reported in patients using this medicine.

Tell your doctor if:

you are taking medicines or have medical conditions which may cause an imbalance of potassium levels in your blood
you suffer from an imbalance of electrolytes (naturally occurring chemicals present in body fluids, that are needed for normal body functions).

If you have not told your doctor or pharmacist about any of the above, tell them before you are given Haldol.

Your doctor will advise you on whether you should receive Haldol or whether to adjust the dose or alter your treatment.

Taking other medicines:

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

In particular, tell your doctor or pharmacist if you are taking any of the following:

medicines used to control depression or mood swings (such as nefazodone, buspirone, venlafaxine, fluvoxamine, fluoxetine, paroxetine, sertraline, lithium, alprazolam, chlorpromazine, citalopram, escitalopram, St John's Wort (Hypericum perforatum) and 'tricyclic antidepressants')
antipsychotic medicines, used to treat mental illness
medicines for nausea and vomiting (such as promethazine, chlorpromazine, dolasetron)
antiviral medicines (such as ritonavir for HIV)
antifungal medication (such as ketoconazole, itraconazole and pentamidine)
medicines known to cause electrolyte imbalance or imbalance of naturally occurring chemicals present in body fluids, that are needed for normal body functions.
alcohol or medicines which make you feel drowsy or slow your reactions, such as sleeping tablets, tranquillisers or strong painkillers
medicines used to lower high blood pressure and heart conditions (such as methyldopa, bepridil, water tablets)
medicines used to treat fast or irregular heartbeats (arrhythmia) such as quinidine, amiodarone, dofetilide, disopyramide, dronedarone, ibutilide, sotalol
Certain cough and cold preparations and weight reduction medicines containing substances such as adrenaline (epinephrine)
medicines that prevent adrenaline (epinephrine) working, such as guanethidine
antibiotics such as rifampicin, erythromycin, levofloxacin, moxifloxacin
medicines used to prevent travel sickness, treat Parkinson's Disease or relieve stomach cramps or spasms (anticholinergics)
medicines used to treat Parkinson's disease, such as levodopa (Levodopa)
medicines used to treat epilepsy (such as carbamazapine, phenobarbital (phenobarbitone))
medicines used to slow or prevent blood clotting (anticoagulants, blood thinners such as phenindione).
methadone (a pain killer or to treat drug addiction).
medicines used for malaria (such as halofantrine)
medicines used for cancer (such as toremifene and vandetanib)

These medicines may be affected by Haldol or may affect how well Haldol works. Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

Lithium

Special monitoring may be needed if you are using lithium and Haldol at the same time.

Tell your doctor straightaway and stop using both medicines if you get:

fever you can't explain or movements you can't control
Confused, disoriented
a headache
balance problems
sleepiness

These are signs of a serious condition.

Effects on driving and operating machinery

Haldol can affect your alertness and ability to drive and operate machinery, particularly when you first start using it, or after a high dose.

Do not drive or operate any tools or machinery until your doctor says it is safe.

Do not drink alcohol. Haldol can increase the effects of alcohol, and might make you feel sleepy and less alert. This means you should be careful how much alcohol you drink

Using Haldol

How it is given:

Haldol will be given as an injection by your doctor or nurse into a muscle in the buttocks.

Haldol should not be given into a vein.

It is usually given every four weeks, however your doctor may lengthen or shorten this time.

Your doctor will decide how much Haldol you will be given. This will depend on your physical conditions such as your age, body weight, your medical history and conditions.

Your doctor will monitor you closely when you start receiving Haldol injection. Your dose and how often the injection is given may be altered, until the medicine controls your symptoms. Follow your doctor's instructions.

If you are elderly or physically unwell, you may need less Haldol. Your doctor may adjust your dose if necessary.

Haldol should not be used in children and adolescents under 18 years of age. This is because it has not been studied in this age group.

If you do not understand the instructions provided with this medicine, ask your doctor or pharmacist for help.

If you forget to use it:

If you have missed your next injection, contact your doctor as soon as possible and make a new appointment.

You should not stop this medicine unless told to do so as your symptoms may return.

If you are given too much (overdose):

Immediately telephone your doctor or the Poisons Information Centre for advice, or go to Accident and Emergency at your nearest hospital. You may need urgent medical attention.

Poisons Information Centre telephone numbers:

Australia: 13 11 26

New Zealand: 0800 POISON or 0800 764 766

Keep these telephone numbers handy

As this medicine will be given to you by your doctor or nurse, it is unlikely that you will be given too much. If you are worried, tell the doctor or nurse.

Signs of overdose of Haldol may include severe tremor, fainting or drowsiness.

While you are given Haldol

Things you must do:

Always follow your doctor's instructions carefully.
Be sure to keep all of your doctor’s appointments so that your progress can be checked. For example, your doctor may want to take an electrocardiogram (ECG) to measure the electrical activity of your heart. Seek your doctor's advice before changing or stopping Haldol treatment.
If you are about to start taking a new medicine, tell your doctor and pharmacist that you are being given Haldol.

Tell your doctor if you become pregnant while using Haldol.

The following problems may occur in newborn babies of mothers that use Haldol in the last 3 months of their pregnancy (the last trimester):

Muscle tremors, stiff or weak muscles
Being sleepy or agitated
Problems breathing or feeding.
Medicine craving (withdrawal)

Things you must not do:

Do not use Haldol to treat any other complaint unless your doctor says so
Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Side Effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some side effects. Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you experience any of the following:

drowsiness or sleepiness
restlessness or difficulty sitting still
difficulty sleeping
constipation
dry mouth
increased salivation
nausea or vomiting
low body temperature
problems with skin such as flaking or peeling of skin, itching, rash, hives, sensitivity to sunlight
excessive sweating
changes in sex drive in both men and women, problems having sex
difficulty getting and keeping an erection (impotence), painful and persistent erection
enlarged breasts in men
problems with menstrual period such as having no periods, painful period, long and heavy periods or changes in menstrual cycles
unexpected production of breast milk
breast pain, discomfort
weight gain or weight loss
muscle stiffness or weakness, abnormal muscle tension, joint stiffness
breakdown of muscle tissue (rhabdomyolysis)
lack of normal facial expressions that sometimes looks like a mask
redness, burning or pain at the site Haldol is given including collection of pus at the site
vision problems such as blurred vision
low blood pressure which may cause dizziness or headache
low blood cell counts such as white blood cells, platelets
abnormal hormone levels in blood such as prolactin, antidiuretic hormone
being unable to pass urine or empty the bladder completely
swelling caused by fluid build-up in the body
low level of sugar in the blood
problems with liver such as jaundice, abnormal blood tests of the liver, liver failure
shaking or tremors
difficulty speaking
uncontrollable twitching or jerking movements of the arms and legs; 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
being unable to move, difficulty opening the mouth
uncontrollable muscle spasms affecting the eyes, head, neck and body
feeling agitated, confused or depressed
Serious mental health problem, such as believing things that are not true (delusions) or seeing, feeling, hearing or smelling things that are not there (hallucinations)
disease of the brain affecting movement, resulting in trembling, rigid posture, slow movements and a shuffling, unbalanced walk (parkinsonism)

Tell your doctor immediately if you notice any of the following as you may need urgent medical care:

difficulty in breathing, or deeper and faster breathing.
allergic reactions with signs such as skin rash, itching, shortness of breath, and/or swelling of the face, lips or throat that may lead to difficulty breathing or swallowing.
a sudden increase in body temperature, extremely high blood pressure, stiff muscles, decreased mental alertness or fits (seizures).
abnormal heart rhythm (in ECG), fast or unusual heartbeat.

Other side effects not listed above may also occur in some people. Tell your doctor if you notice any other effects.

After using Haldol

Storage

Keep Haldol Injection in the pack until it is time to use them.

Keep Haldol Injection in a cool dry place where the temperature is below 25°C. Protect it from light.

Keep your medicines where children cannot reach them. A locked cupboard at least one-and-a-half metres (1.5 m) above the ground is a good place to store medicines.

Do not use this medicine after the expiry date which is stated on the label or carton. The expiry date refers to the last day of that month.

Do not store Haldol, or any other medicine, in the bathroom or near a sink. Do not leave medicines in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop using Haldol Injection, or your medicine has passed its expiry date, ask your pharmacist what to do with any medicine which may be left over.

Product Description

What it looks like

Haldol Oily Injection is a slightly amber and viscous solution, and comes in 1 mL or 3 mL amber glass ampoules. Each pack contains 5 ampoules.

Ingredients

Each mL of Haldol Injection contains

50 mg haloperidol (as decanoate) as the active ingredient
other ingredients: sesame oil vehicle, benzyl alcohol

Contains sesame seed products.

Sponsor

JANSSEN-CILAG Pty Ltd
1-5 Khartoum Road Macquarie Park NSW 2113
Australia
Telephone: 1800 226 334
NZ Office: Auckland New Zealand
Telephone: 0800 800 806

Registration number

The Australian Registration Numbers are:

Haldol Decanoate 50 mg/1 mL Injection - AUST R 13302

Haldol Decanoate 150 mg/3 mL Injection - AUST R 46901

This leaflet was prepared in September 2021.

Published by MIMS November 2021

BRAND INFORMATION

Brand name

Haldol Decanoate

Active ingredient

Haloperidol decanoate

Schedule

1 Name of Medicine

Haloperidol decanoate.

2 Qualitative and Quantitative Composition

Each 1 mL injection contains 50 mg haloperidol (present as haloperidol decanoate 70.52 mg) and each 3 mL injection contains 150 mg haloperidol (present as haloperidol decanoate 211.56 mg).

Excipient(s) of known effect.

Contains sesame seed products.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The oily injection for intramuscular injection (IM) is a slightly amber, slightly viscous solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Haldol Decanoate is indicated for the maintenance therapy of psychoses in adults; particularly for patients requiring prolonged parenteral neuroleptic therapy.

4.2 Dose and Method of Administration

Administration.

Haldol Decanoate should be administered by deep intramuscular injection into the gluteal region. A 2 inch long, 21 gauge needle is recommended. The maximum volume per injection site should not exceed 3 mL. The recommended interval between doses is 4 weeks. It is recommended to alternate between the two gluteal muscles for subsequent injections.
Do not administer intravenously.
Patients must be previously stabilised on oral haloperidol before converting to Haldol Decanoate.
Treatment initiation and dose titration must be carried out under close clinical supervision. The starting dose of Haldol Decanoate should be based on the patient's clinical history, physical condition and response to the current oral haloperidol dose. Patients must always be maintained on the lowest effective dose.

Dosage.

Adults.

See Table 1.

Special populations.

Paediatrics.

The safety and efficacy of Haldol Decanoate in children and adolescents below 18 years of age have not been established. No data are available.

Elderly.

See Table 2.

Renal impairment.

The influence of renal impairment on the pharmacokinetics of haloperidol has not been evaluated. No dose adjustment is recommended, but caution is advised when treating patients with renal impairment. However, patients with severe renal impairment may require a lower initial dose, with subsequent adjustments at smaller increments and at longer intervals than in patients without renal impairment (see Section 5.2 Pharmacokinetic Properties, Special populations, Renal impairment).

Hepatic impairment.

The influence of hepatic impairment on the pharmacokinetics of haloperidol has not been evaluated. Since haloperidol is extensively metabolised in the liver, it is recommended to halve the initial dose, and adjust the dosage with smaller increments and at longer intervals than in patients without hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use, Hepatobiliary concerns; Section 5.2 Pharmacokinetic Properties, Special populations, Hepatic impairment).
Clinical experience with Haldol Decanoate at doses greater than 300 mg (6 mL) per month has been limited.

4.3 Contraindications

Haldol Decanoate is contraindicated in: in individuals who are hypersensitive to haloperidol or to any of the excipients (crossreactivity of sesame oil in patients with a peanut allergy may occur); comatose states from any cause; the presence of central nervous system (CNS) depression due to alcohol or other depressant drugs; patients with significant depressive states; patients with previous spastic diseases; Parkinson's syndrome, except in the case of dyskinesias due to levodopa treatment; senile patients with pre-existing Parkinson-like symptoms; patients with dementia with Lewy bodies; in patients with progressive supranuclear palsy.

4.4 Special Warnings and Precautions for Use

Mortality.

Rare cases of sudden death have been reported in psychiatric patients receiving antipsychotic drugs, including Haldol Decanoate (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 has not yet been elucidated.
Haldol Decanoate is not indicated for the treatment of dementia-related behavioural disturbances.

Cardiovascular effects.

Very rare reports of QTc interval prolongation and/or ventricular arrhythmias, in addition to sudden death have been reported in patients receiving haloperidol (see Section 4.8 Adverse Effects (Undesirable Effects)). They may occur more frequently with high doses, high plasma concentrations, in predisposed patients or with QTc interval that exceeds 500 ms.
Higher than recommended doses and intravenous administration of haloperidol appear to be associated with a higher risk of QTc prolongation and/or ventricular arrhythmias, and torsades de pointes (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose). Since QTc prolongation has been observed during Haldol Decanoate treatment, it is advised to be particularly cautious in patients with QTc prolonging conditions (QTc syndrome, electrolyte imbalance (especially hypokalaemia and hypomagnesaemia), drugs known to prolong QT, cardiovascular diseases, hypothyroidism, family history of QTc prolongation) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
A baseline ECG is recommended before treatment. During therapy, the need for ECG monitoring for QTc interval prolongation and for ventricular arrhythmias must be assessed in all patients. Whilst on therapy, it is recommended to reduce the dose if QTc is prolonged, but haloperidol must be discontinued if the QTc exceeds 500 ms.
Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for ventricular arrhythmias and must be corrected before treatment with haloperidol is started. Therefore, baseline and periodic electrolyte monitoring is recommended.
Haldol Decanoate must not be administered intravenously.
Tachycardia and hypotension (including orthostatic hypotension) have also been reported in occasional patients (see Section 4.8 Adverse Effects (Undesirable Effects)).

Cerebrovascular events.

In randomized, placebo controlled clinical trials in the dementia population, there was an approximately 3-fold increased risk of cerebrovascular adverse events with some atypical antipsychotics. Observational studies comparing the stroke rate in elderly patients exposed to any antipsychotic to the stroke rate in those not exposed to such medicinal products reported an increased stroke rate among exposed patients. This increase may be higher with all butyrophenones, including haloperidol. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other patient populations. Haldol Decanoate must be used with caution in patients with risk factors for stroke.

Neuroleptic malignant syndrome.

As with other neuroleptic drugs, a symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported. Cardinal features of NMS are hyperthermia, hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure), and increased serum creatine phosphokinase levels. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. Hyperthermia is often an early sign of this syndrome. NMS is potentially fatal, requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment. Dantrolene and bromocriptine have been used for the treatment of NMS.
Signs of autonomic dysfunction such as tachycardia, labile arterial pressure and sweating may precede the onset of hyperthermia thereby acting as early warning signs. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.
Hyperpyrexia and heat stroke not associated with the above symptom complex have also been reported with Haldol Decanoate.

Extrapyramidal symptoms.

Extrapyramidal reactions such as Parkinson-like symptoms, akathisia or dystonic reactions occur frequently with antipsychotics including oral and injectable haloperidol. These have been observed with Haldol Decanoate. In most patients, Parkinson-like symptoms, when first observed, were usually mild to moderately severe and usually reversible. They are more commonly observed during the first few days of treatment, however Parkinson rigidity, tremor and akathisia tend to appear less rapidly. They sometimes remit spontaneously as treatment continues, or can be relieved by the use of antiparkinson medication or a reduction in dose. Antiparkinson drugs of the anticholinergic type should only be used when required because of their potential to impair the efficacy of Haldol Decanoate. If concomitant antiparkinson medication is required, it may have to be continued after stopping Haldol Decanoate if its excretion is faster than that of Haldol Decanoate in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered.
Other types of neuromuscular reactions (motor restlessness, dystonia, akathisia, hyper-reflexia, opisthotonos, oculogyric crisis) have been reported far less frequently, but were often more severe.
Akathisia is best managed by a reduction in dosage in conjunction with the temporary use of an oral antiparkinson drug. Dystonias, which can lead to laryngeal spasm or bronchospasm, may be controlled by amylobarbitone or injectable antiparkinson agents. Extrapyramidal reactions appear to be dose related.

Tardive dyskinesia.

Tardive dyskinesia, a syndrome consisting of potentially irreversible involuntary, dyskinetic movements, is known to occur in patients treated with neuroleptics with antipsychotic properties and other drugs with substantial neuroleptic activity. The syndrome is characterised by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of the extremities. Tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The symptoms are persistent and although the dyskinetic syndrome may remit partially or completely if the medication is withdrawn, it is irreversible in some patients.
The prevalence of the syndrome appears to be highest among the elderly, especially elderly women. At the present time there is uncertainty as to whether neuroleptic drugs differ in their potential to cause tardive dyskinesia. There is no known effective treatment for tardive dyskinesia; antiparkinsonian agents usually do not alleviate the symptoms of this syndrome. Since there is a significant prevalence of this syndrome associated with the use of neuroleptic drugs, and 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. If manifestations of tardive dyskinesia are detected during the use of a neuroleptic, the drug should be discontinued. It is suggested that the dosage of all antipsychotic agents be progressively reduced with a view to discontinuation if possible. Should it be necessary to reinstitute treatment or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome, and, if the medication is stopped at that time, the full syndrome may not develop.
The risk of a patient developing tardive dyskinesia and of the syndrome becoming irreversible appear to increase with the duration of treatment and the total amount of drugs administered, 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. Continued use of neuroleptics should be periodically reassessed.

Tardive dystonia.

Tardive dystonia, which might be observed in the absence of other symptoms of the above syndrome, has also been reported. Tardive dystonia is characterised by delayed onset of choreic or dystonic movements, is often persistent, and has the potential of becoming irreversible.

Seizures/ convulsions.

Seizures can be triggered by haloperidol. If indicated, adequate anticonvulsant therapy should be concomitantly maintained. Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g. alcohol withdrawal and brain damage).

Hepatobiliary concerns.

Since haloperidol is metabolised in the liver, dosage adjustment and careful observation of patients with hepatic impairment is recommended (see Section 4.2 Dose and Method of Administration, Special populations, Hepatic impairment; Section 5.2 Pharmacokinetic Properties, Special populations, Hepatic impairment). Impaired liver function and/or jaundice or hepatitis, most often cholestatic, has been reported (see Section 4.8 Adverse Effects (Undesirable Effects)).

Endocrine system concerns.

Patients with thyrotoxicosis.

Antipsychotic medication, including Haldol Decanoate, may result in severe neurotoxicity (rigidity, inability to walk or talk). Antipsychotic treatment in these patients should always be accompanied by appropriate monitoring and therapy.
Hormonal effects of antipsychotic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligomenorrhoea or amenorrhoea. Very rare cases of hypoglycaemia and of syndrome of inappropriate antidiuretic hormone secretion have been reported (see Section 4.8 Adverse Effects (Undesirable Effects)).

Venous thromboembolism.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Haldol Decanoate and preventive measures undertaken.

Weight gain.

Clinically significant weight gain has been reported in patients taking Haldol Decanoate. Patients taking antipsychotic medications, including Haldol Decanoate should undergo regular monitoring of weight and the testing of other parameters (e.g. blood glucose, haemoglobin A1C) that would be appropriate in the setting of significant weight gain. Clinicians should individualise treatment decisions based on such monitoring.

Treatment initiation.

It is recommended that patients to be treated with Haldol Decanoate be treated initially with oral haloperidol to exclude the possibility of severe unexpected sensitivity to haloperidol.
Haldol Decanoate should be administered with caution to:
Patients with severe cardiovascular disorders, because of the possibility of transient hypotension and/or precipitation of anginal pain. When antihypertensives and haloperidol are used concomitantly, the use of vasopressors such as noradrenaline (norepinephrine) may be indicated if the resulting hypotension is prolonged and severe. Adrenaline (epinephrine) should not be used since haloperidol may reverse its action and cause profound hypotension.
Patients receiving anticonvulsant medications with a history of seizures, or with EEG abnormalities, because haloperidol may lower the convulsive threshold (see Section 4.4 Special Warnings and Precautions for Use, Seizures/ convulsions).
Patients who are elderly or debilitated. These patients should be observed for evidence of over sedation, which, unless alleviated, could result in complications such as terminal stasis pneumonia.
Patients with thyrotoxicosis (see Section 4.4 Special Warnings and Precautions for Use, Endocrine system concerns).
Patients with known allergies or with a history of allergic reactions to drugs.
Patients receiving anticoagulants (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
When Haldol Decanoate is used to control mania in bipolar disorders, there may be a rapid mood swing to depression.
Antiemetic action may obscure the diagnosis of an underlying condition characterised by nausea and vomiting.
It is advisable to carefully observe the patients who receive haloperidol decanoate for a long period in order to identify any changes in the skin or eyes. Oculocutaneous changes have been observed following use of butyrophenones structurally related to haloperidol.
If concomitant antiparkinson medication is required, it may have to be continued after Haldol Decanoate is discontinued because of the prolonged action of haloperidol decanoate. If both drugs are discontinued simultaneously, extrapyramidal symptoms may occur.

Patients with depression.

As with all antipsychotic agents, Haldol Decanoate should not be used alone where depression is predominant.

Use in the elderly.

Lower initial doses and more gradual adjustments are recommended for elderly or debilitated patients (see Section 4.2 Dose and Method of Administration).

Paediatric use.

Safety and efficacy in children have not been established, therefore, Haldol Decanoate is not recommended for use in the paediatric age group.

Effects of laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Cardiovascular effects.

As with other antipsychotic medicines, caution is advised when Haldol Decanoate is used in combination with medications known to prolong the QTc interval. (see Section 4.4 Special Warnings and Precautions for Use, Cardiovascular effects). Examples include:
class IA antiarrhythmics (e.g. disopyramide, quinidine);
class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
certain antidepressants (e.g. citalopram, escitalopram);
certain antibiotics (e.g. erythromycin, levofloxacin, moxifloxacin);
certain antifungals (e.g. pentamidine);
certain antimalarials (e.g. halofantrine);
certain gastrointestinal drugs (e.g. dolasetron);
certain drugs used in cancer (e.g. toremifene, vandetanib);
certain other drugs (e.g. bepridil, methadone).
This list is not exhaustive.
It is recommended that concomitant use of other antipsychotic drugs be avoided.
Caution is advised when Haldol Decanoate is used in combination with medicines known to cause electrolyte imbalance (see Section 4.4 Special Warnings and Precautions for Use, Cardiovascular effects).

Medicines that may increase haloperidol plasma concentrations.

Haloperidol is metabolised by several routes (see Section 5.2 Pharmacokinetic Properties, Metabolism). The major pathways are glucuronidation and ketone reduction. The cytochrome P450 enzyme system is also involved, particularly CYP3A4 and to a lesser extent, CYP2D6. Inhibition of these routes of metabolism by another drug or a decrease in CYP 2D6 enzyme activity may result in increased haloperidol concentrations. The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme activity may be additive (see Section 5.2 Pharmacokinetic Properties, Metabolism). Based on limited and sometimes conflicting information, the average increase in haloperidol plasma concentrations when a CYP3A4 and/or CYP2D6 inhibitor was co-administered generally ranged between 20 and 40%, although in some cases, average increases of up to 100% have been reported. Examples of drugs that may increase haloperidol plasma concentrations (based on clinical experience or drug interaction mechanism) include:
CYP3A4 inhibitors - alprazolam; itraconazole, ketoconazole, and some other azoles; nefazodone; certain antivirals.
CYP2D6 inhibitors - chlorpromazine; promethazine; quinidine; paroxetine, sertraline, venlafaxine, duloxetine and some other antidepressants.
Combined CYP3A4 and CYP2D6 inhibitors - fluoxetine, fluvoxamine; ritonavir.
Uncertain mechanism - buspirone.
This list is not exhaustive.
Increased haloperidol plasma concentrations may result in an increased risk of adverse events, including QTc interval prolongation (see Section 4.4 Special Warnings and Precautions for Use, Cardiovascular effects). Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day).
It is recommended that patients who take haloperidol concomitantly with such medicinal products be monitored for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol, and the Haldol dose be decreased as deemed necessary.
Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.

Medicines that may decrease haloperidol plasma concentrations.

Coadministration of haloperidol with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of haloperidol to such an extent that efficacy may be reduced. Examples (based on clinical experience or drug interaction mechanism) include: carbamazepine, phenobarbital, phenytoin, rifampicin, St John's Wort (Hypericum perforatum).
This list is not exhaustive.
Enzyme induction may be observed after a few days of treatment. Maximal enzyme induction is generally seen in about 2 weeks and may then be sustained for the same period of time after the cessation of therapy with the medicinal product. Therefore, during combination treatment with inducers of CYP3A4, it is recommended that patients be monitored, and the Haldol Decanoate dose increased, or the dosage interval adjusted, as deemed necessary. After withdrawal of the CYP3A4 inducer, the concentration of haloperidol may gradually increase and therefore it may be necessary to reduce the dose of Haldol, or adjust the dosage interval.

Effects of Haldol Decanoate on other medicines.

Although haloperidol decanoate does not provoke a respiratory depression, it can have a potentiating effect on CNS depressants such as anaesthetics, opiates, hypnotics (barbiturates), sedatives, strong analgesics and alcohol.
An enhanced CNS effect (disorientation, memory loss, mental retardation, aggression, irritability) when combined with methyldopa has been reported.
Haloperidol decanoate may antagonise the action of adrenaline (epinephrine) and other sympathomimetic agents and reverse the blood pressure lowering effects of adrenergic blocking agents such as guanethidine. Haldol Decanoate may impair the antiparkinsonian effects of levodopa and other dopamine agonist medicines.
Haloperidol is an inhibitor of CYP2D6. It inhibits the metabolism of tricyclic antidepressants, increasing blood levels of these drugs. This may result in increased tricyclic antidepressant toxicity.

Other forms of interaction.

An encephalopathic syndrome with reported symptoms including weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, leukocytosis, elevated serum enzymes and BUN and coma, followed by irreversible brain damage, has occurred in a few patients treated with lithium plus haloperidol; a causal relationship has not been established. However, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment must be discontinued should such signs appear.
Haloperidol has been reported to interfere with the activity of phenindione and coumarin anticoagulants.
The use of alcohol with this drug should be avoided due to possible additive effects and hypotension.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no human data on the effects of haloperidol on male and female fertility. In female rats, administration of haloperidol induced estrus cycle disruptions, and in female mice, subcutaneous administration of haloperidol prior to ovulation induced delays in implantation, cleavages and blastocoele formation. In male rats, oral administration of haloperidol prior to mating reduced fertility, increased preimplantation 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. These studies used various dose levels and in some cases a no effect level was not established. The significance of these findings for human exposure to therapeutic doses of haloperidol decanoate is unknown.
(Category C)
There have been isolated case reports of birth defects following foetal exposure to haloperidol in combination with other drugs.

Nonteratogenic class effect.

Neonates exposed to antipsychotic medicines (including Haldol Decanoate) 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 feeling disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self limited; in other cases neonates have required additional medical treatment or monitoring.
Haldol Decanoate should be used during pregnancy only if the anticipated benefit outweighs the risk and the administered dose and duration of treatment should be as low and as short as possible.
Withdrawal emergent syndromes in neonates, following long-term, in utero exposure to haloperidol, have been reported.
In pregnant rodents, administration of haloperidol during the period of organogenesis has produced adverse effects including embryolethality, gross malformations (cleft palate, neural tube defects), and reduced brain and bodyweight and behavioural effects in offspring. The significance of these findings for human exposure to therapeutic doses of haloperidol decanoate is unknown.
Haloperidol is excreted in human breast milk. Small amounts of haloperidol have been detected in plasma and urine of breast fed newborns of mothers treated with haloperidol. There is insufficient information on the effects of haloperidol in breast-fed infants. A decision must be made whether to discontinue breastfeeding or to discontinue Haldol Decanoate therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

4.7 Effects on Ability to Drive and Use Machines

Haldol Decanoate 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)

Clinical trial data.

Comparator and open-label trial data - adverse drug reactions reported at ≥ 1% incidence.

The safety of Haldol Decanoate (15-500 mg/month) was evaluated in 410 subjects who participated in 13 clinical trials in the treatment of schizophrenia or a schizoaffective disorder. Adverse reactions reported by ≥ 1% of Haldol Decanoate-treated subjects in these trials are shown in Table 3.

Comparator and open-label trial data - adverse drug reactions reported at < 1% incidence.

Additional adverse reactions that occurred in < 1% of Haldol Decanoate treated subjects either of the above trial data are listed in Table 4.

Adverse reactions relating to the active moiety that were identified in clinical trials with haloperidol (non-decanoate formulations) are listed in Table 5.

Postmarketing data.

Adverse events first identified as adverse reactions during postmarketing experience with haloperidol, presented by frequency category based on spontaneous reporting rates, are included in Table 6. The postmarketing review was based on review of all cases including haloperidol and haloperidol decanoate products. In each table, the frequencies are provided according to the following convention: very common ≥ 1/10, common ≥ 1/100 to < 1/10, uncommon ≥ 1/1,000 to < 1/100, rare ≥ 1/10,000 to < 1/1,000, very rare < 1/10,000, including isolated reports.

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 https://www.tga.gov.au/reporting-problems.

4.9 Overdose

While overdosage is less likely to occur with parenteral than with oral medication, information pertaining to oral haloperidol is presented, modified only to reflect the extended duration of action of haloperidol decanoate.

Symptoms.

In general, the symptoms of overdosage would be an exaggeration of known pharmacological effects and adverse reactions, the most prominent of which would be severe extrapyramidal reactions, hypotension or sedation.
The patient would appear comatose with respiratory depression and hypotension that could be severe enough to produce a shock-like state. The extrapyramidal reaction would be manifest by muscular weakness or rigidity and generalised or localised tremor, as demonstrated by akinetic or agitans types, respectively. With accidental overdosage, hypertension rather than hypotension occurred in a two year old child.
There is a possibility of ventricular arrhythmias, sometimes associated with QTc interval prolongation.

Treatment.

There is no specific antidote. Treatment is supportive. Dialysis is not recommended in the treatment of overdose because it removes only very small amounts of haloperidol (see Section 5.2 Pharmacokinetic Properties, Special populations, Renal impairment). A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy. Respiratory depression may be counteracted by artificial respiration and mechanical respirators.
ECG and vital signs should be monitored and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate antiarrhythmic measures.
Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma or concentrated albumin, and vasopressor agents, such as noradrenaline (norepinephrine). Adrenaline (epinephrine) must not be used as it may cause profound hypotension in the presence of haloperidol. In case of severe extrapyramidal reactions, antiparkinson medication should be administered and continued for several weeks. Antiparkinson medication must then be withdrawn very cautiously as extrapyramidal symptoms may emerge.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code N05AD01.

Mechanism of action.

Haloperidol decanoate is a long acting form of haloperidol. The basic effects of haloperidol decanoate are the same as those of haloperidol with the exception of duration of action. When it is administered as an intramuscular depot injection in sesame oil, esterases present in the blood and tissues hydrolyse haloperidol decanoate to provide a slow release of the active neuroleptic haloperidol from the depot into the systemic circulation.
Haloperidol is a potent central dopamine type 2 receptor antagonist, and at recommended dosages, has low alpha-1 antiadrenergic activity and no antihistaminergic or anticholinergic activity.

Clinical trials.

No data available.

Pharmacodynamic effects.

Haloperidol suppresses delusions and hallucinations as a direct consequence of blocking dopaminergic signalling in the mesolimbic pathway. The central dopamine blocking effect has activity on the basal ganglia (nigrostriatal bundles). Haloperidol causes effective psychomotor sedation, which explains the favourable effect on mania and other agitation syndromes.
The activity on the basal ganglia probably underlies the undesirable extrapyramidal motor effects (dystonia, akathisia and parkinsonism).
The antidopaminergic effects of haloperidol on lactotropes in the anterior pituitary explain hyperprolactinaemia due to inhibition of dopamine-mediated tonic inhibition of prolactin secretion.

5.2 Pharmacokinetic Properties

Absorption.

Administration of haloperidol decanoate as a depot IM injection results in a slow and sustained release of haloperidol. The plasma concentrations rise gradually, usually peaking within 3 to 9 days after injection and falling thereafter with an apparent half-life of about 3 weeks. Steady-state plasma levels were reached in 2-4 months in chronic psychotic patients receiving monthly injections.

Distribution.

Mean haloperidol plasma protein binding in adults is approximately 88 to 92%. There is a high inter subject variability for plasma protein binding. Haloperidol is rapidly distributed to various tissues and organs, as indicated by the large volume of distribution (mean values 8 to 21 L/kg after intravenous dosing). Haloperidol crosses the blood brain barrier easily. It also crosses the placenta and is excreted in breast milk.

Metabolism.

Haloperidol is extensively metabolised in the liver. The main metabolic pathways of haloperidol in humans include glucuronidation, ketone reduction, oxidative N dealkylation and formation of pyridinium metabolites. The metabolites of haloperidol are not considered to make a significant contribution to its activity; however, the reduction pathway accounts for some of the biotransformation, and back-conversion of the reduced metabolite of haloperidol to haloperidol cannot be fully ruled out. The cytochrome P450 enzymes CYP3A4 and CYP2D6 are involved in haloperidol metabolism. Inhibition or induction of CYP3A4, or inhibition of CYP2D6, may affect haloperidol metabolism. A decrease in CYP2D6 enzyme activity may result in increased haloperidol concentrations.

Elimination.

The terminal elimination half-life of haloperidol after intramuscular injection with haloperidol decanoate is on average 3 weeks. This is longer than for the non-decanoate formulations, where the haloperidol terminal elimination half-life is on average 24 hours. Haloperidol apparent clearance after extravascular administration ranges from 0.9 to 1.5 L/h/kg and is reduced in poor metabolisers of CYP2D6 substrates. The inter subject variability (coefficient of variation, %) in haloperidol clearance was estimated to be 44% in a population pharmacokinetic analysis in patients with schizophrenia. After intravenous haloperidol administration, 21% of the dose was eliminated in the faeces and 33% in the urine. Less than 3% of the dose is excreted unchanged in the urine.

Linearity/non-linearity.

The pharmacokinetics of haloperidol following intramuscular injections of haloperidol decanoate are dose related. The relationship between dose and plasma haloperidol level is approximately linear for doses below 450 mg.