Consumer medicine information

Stemetil

Prochlorperazine

BRAND INFORMATION

Brand name

Stemetil

Active ingredient

Prochlorperazine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Stemetil.

What is in this leaflet

This leaflet answers some common questions about Stemetil.

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 you taking Stemetil against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

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

What Stemetil is used for

Stemetil belongs to a group of medicines called phenothiazines. It helps to correct chemical imbalances in the brain, allowing it to function correctly. These chemicals may also affect the parts of the brain which control nausea (feeling sick) and vomiting.

Stemetil is used to treat nausea, vomiting and dizziness due to various causes, including migraine (severe headache).

Your doctor may have prescribed Stemetil for another reason.

Ask your doctor if you have any questions about why Stemetil has been prescribed for you.

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

Stemetil is not recommended for use in children (under the age of 2 years or children under 10kg in weight) because children may develop unusual face and body movements.

Before you take it

When you must not take it

Do not take Stemetil if you have an allergy to:

  • Stemetil
  • the group of medicines called phenothiazines
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to Stemetil may include:

  • shortness of breath, wheezing or difficulty in breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

You should not take Stemetil if you have any of the following medical conditions:

  • shock
  • disease of the blood with a low number of blood cells
  • yellowing of the skin and/or eye, also called jaundice

Stemetil must not be given to anyone who is unconscious or in a coma.

Do not take any medicines that cause drowsiness while you are taking Stemetil.

Do not take Stemetil after the expiry date (EXP) printed on the pack. If you take this medicine after the expiry date has passed, it may not work as well.

Do not take Stemetil if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking Stemetil, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant. Like most phenothiazine medicines, Stemetil is not recommended for use during pregnancy. If there is a need to take Stemetil during your pregnancy, your doctor will discuss with you the benefits and risks of using it.

Tell your doctor or pharmacist if you are breastfeeding or plan to breastfeed. It is recommended that you do not breastfeed while taking Stemetil, as it is not known whether Stemetil passes into breast milk.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

  • phaechromocytoma, a rare tumour of the adrenal glands which sit near the kidneys.
  • Parkinson's disease, a disease of the brain affecting movement which causes trembling, rigid posture, slow movement and a shuffling, unbalanced walk.
  • myasthenia gravis, a disease of the muscles causing drooping eyelids, double vision, difficulty in speaking and swallowing and sometimes muscle weakness in the arms or legs
  • kidney problems
  • heart and blood vessel problems, low blood pressure
  • blood clots
  • liver disease
  • prostate problems
  • bowel problems
  • epilepsy, seizures or fits
  • low blood calcium levels
  • decreased thyroid activity
  • glaucoma, a condition in which there is usually a build-up of fluid in the eye
  • neuroleptic malignant syndrome, a reaction to some medicines with a sudden increase in body temperature, extremely high blood pressure and severe convulsions
  • a reaction to some medicines with uncontrollable twitching or jerking movements of the arms and legs.
  • dementia
  • diabetes
  • a low number of white blood cells.

Tell your doctor if you are about to have any surgery which requires a general anaesthetic.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Stemetil.

Taking other medicines

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

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

  • some medicines used to control depression or mood swings or mental illness such as lithium
  • medicines metabolised by CYP2D6 enzymes such as amitriptyline
  • alcohol
  • desferrioxamine, a drug used in iron overdose
  • medicines used for cancer such as procarbazine
  • some medicines used to control epilepsy such as phenobarbital and carbamazepine
  • antibiotics used to treat infections
  • medicines used to treat Parkinson's disease such as levodopa
  • medicines used for the treatment of diabetes
  • anticholinergic medicines which are used to relieve stomach cramps, spasms and travel sickness
  • atropine, a medicine which may be used in some eye drops or cough and cold preparations
  • some oral medicines used to prevent your blood from clotting
  • medicines used to treat high blood pressure or heart problems such as clonidine, guanethidine and propranolol
  • medicines used to treat fluid build-up in your body
  • medicines used to treat a fast or irregular heart beat e.g. amiodarone, quinidine, disopyramide.
  • medicines that can slow your heart beat e.g. diltiazem, verapamil.
  • medicines that can reduce potassium levels in the blood e.g. diuretics, laxatives.
  • other medicines that can affect your heart rate e.g. methadone, pentamidine.
  • antacids containing magnesium, aluminium and calcium salts, oxides and hydroxides
  • adrenaline used for severe allergic reactions
  • amfetamine.

These medicines may be affected by Stemetil or may affect how well it works. You may need different amounts of your medicine or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Stemetil.

How to take it

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

Your doctor or pharmacist will tell you how much Stemetil you will need to take each day. This depends on your condition and whether or not you are taking any other medicines.

Adults' dose:
The usual recommended dose for nausea and vomiting is 1 or 2 tablets two to three times daily. If you are not able to take a tablet, then one 25mg suppository or a 1mL (12.5mg) injection is the recommended dose.

The usual recommended dose for dizziness is 1 or 2 tablets three to four times daily.

Children's dose:
The recommended dose for nausea, vomiting and dizziness is 1 tablet two to three times a day.

How to take it

Tablets:
Swallow Stemetil tablets whole with a full glass of water. Do not chew the tablets.

Suppository:

  1. Stemetil may be given as a suppository. First wash your hands well with soap and water, then follow these instructions: Go to the toilet and empty your bowels if possible. Do not strain.
  2. Feel the suppository through its plastic shell. If it feels very soft, chill it in the fridge or cool it by holding it under cold water for several minutes
  3. Remove the suppository from its shell
  4. Moisten the suppository by dipping it briefly in cool water
  5. Put one foot up on the side of the bath or toilet, raising the knee to the chest
  6. Insert the suppository, pointed end first, gently into the rectum (back passage)
  7. Try not to go to the toilet for at least one hour to allow the suppository to work.

Injection:
Stemetil may be given as an injection into a muscle. Stemetil injection should only be given by a doctor, nurse or other trained person.

When to take it

It does not matter if you take Stemetil before or after food.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

How long to take it

Continue taking Stemetil for as long as your doctor tells you.

If you take too much (overdose)

Do not try to vomit.

Immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26 in Australia or 0800 POISON, 0800 764 766 in New Zealand) or go to Accident and Emergency at your nearest hospital if you think that you, or anyone else, has taken too much Stemetil. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of overdose may include the following:

  • coma
  • restlessness, shaking, muscle twitching, muscle weakness, spasm
  • confusion
  • excitement or agitation
  • low blood pressure
  • irregular or fast heart beat
  • decrease in body temperature
  • small or large pupils in the eye
  • difficulty in swallowing or breathing
  • blue skin
  • feeling of tiredness, drowsiness or lack of energy
  • difficulty in speaking
  • convulsions.

Your doctor or pharmacist has information on how to recognise and treat an overdose. Ask your doctor or pharmacist if you have any concerns.

While you are taking it

Things you must do

Tell your doctor immediately if you notice any uncontrolled movements of the tongue, face, mouth or jaw, such as puffing of the cheeks, puckering of the mouth or chewing movements. These are symptoms of a very rare condition called tardive dyskinesia, which may develop in people taking phenothiazine medicines, including Stemetil.

The condition is more likely to occur during long term treatment with Stemetil, especially in elderly women. In very rare cases, this may be permanent.

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

If you are about to be started on any new medicines, tell your doctor, dentist or pharmacist that you are taking Stemetil.

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

If you become pregnant while taking Stemetil, tell your doctor immediately.

Things you must not do

Do not give Stemetil to anyone else, even if they have the same condition as you.

Do not take Stemetil to treat any other complaints unless your doctor or pharmacist tells you to.

Do not stop taking Stemetil, or lower the dosage, even if you are feeling better, without checking with your doctor. If you stop taking Stemetil 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 Stemetil you take each day before stopping completely.

Things to be careful of

Be careful driving or operating machinery until you know how Stemetil affects you.

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

Make sure you know how you react to Stemetil 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.

If you drink alcohol, dizziness or light-headedness may be worse.

If Stemetil makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position. Getting up slowly may help.

Be careful when drinking alcohol while taking Stemetil. Combining Stemetil and alcohol can make you more sleepy, dizzy or light-headed. Your doctor may suggest you avoid alcohol while you are being treated with Stemetil.

It is advised to avoid exposure to direct sunlight during treatment. If outdoors, wear protective clothing and use at least a 15+ sunscreen. Stemetil 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.

Make sure you keep cool in hot weather and keep warm in cool weather. Stemetil may affect the way your body reacts to temperature changes.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Stemetil.

Stemetil helps most people with nausea, vomiting and dizziness, but it may have unwanted side effects in a few people.

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 of the side effects. If you are over 65 years of age you may have an increased chance of getting side effects.

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

If you get any side effects, do not stop taking Stemetil without first talking to your doctor or pharmacist.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • constipation
  • dry mouth
  • drowsiness
  • restlessness
  • trembling, rigid posture, mask-like face, slow movements and a shuffling unbalanced walk
  • uncontrollable twitching, jerking or writhing movements
  • blurred vision
  • low blood pressure.

The following side effects are less common:

  • changes in heart beats
  • swelling of the hands, ankles or feet
  • skin rash
  • for females: unusual secretion of breast milk, irregular or stopping of periods
  • for males: breast enlargement, difficulty in ejaculating, getting or maintaining an erection, or persistent painful erection
  • severe pain in the stomach with bloating, cramps and vomiting
  • difficulty passing urine
  • yellowing of the skin and/or eyes
  • headache
  • insomnia
  • seizures
  • agitation
  • dizziness
  • difficulty in breathing
  • brownish deposits in the eyes
  • stuffy nose.

If any of the following happen, tell your doctor or pharmacist immediately or go to Accident and Emergency at your nearest hospital:

  • unusual muscle tone or spasms causing distortion of the body in children
  • shortness of breath, wheezing or difficulty in breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.
  • sudden increase in body temperature, extremely high blood pressure and severe convulsions.

These are very serious side effects.

You may need urgent medical attention or hospitalisation.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Stemetil

Storage

Stemetil ampoules for injection should be stored at a pharmacy or hospital. The injection should be kept below 25°C and protected from light.

Keep Stemetil suppositories in a cool dry place where the temperature stays below 25°C. Protect from light.

Keep Stemetil tablets in a cool dry place where the temperature stays below 30°C. Protect from light.

Keep your Stemetil in the pack until it is time to take them. If you take the tablets or suppositories out of the pack, they may not keep well.

Do not store Stemetil or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor or pharmacist tells you to stop taking Stemetil, or the medicine has passed its expiry date, ask your pharmacist what to do with any that are left over.

Product Description

What it looks like

Stemetil tablets* are white, round and marked with "S". Tablets are available in packs of 25.

Stemetil suppositories* are cream, smooth, torpedo shaped and are available in packs of 5.

Stemetil for injection is a clear liquid in a 1mL glass ampoule, in a pack of 10 ampoules.

Ingredients

Stemetil tablets* contain:

prochlorperazine maleate 5mg (active ingredient), wheat starch, calcium hydrogen phosphate dihydrate, magnesium stearate, sodium lauryl sulfate.

Stemetil suppositories* contain:

  • prochlorperazine base equivalent to 25mg prochlorperazine maleate (active ingredient)
  • suppository base (saturated vegetable fat).

Stemetil ampoules contain:

  • prochlorperazine mesilate 12.5 mg/mL (active ingredient)
  • sodium chloride
  • sodium sulfite
  • sodium metabisulfite
  • monoethanolamine
  • water for injection.

Manufacturer/Sponsor

Stemetil is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Toll Free Number (medical information): 1800 818 806
Email: [email protected]

Stemetil is supplied in New Zealand by:

sanofi-aventis new zealand limited
Level 8,
56 Cawley Street
Ellerslie
Auckland

Registration Numbers:

Stemetil tablets
AUST R 27564

Stemetil suppositories
25mg - AUST R 27557

Stemetil ampoules for injection
AUST R 27555

Date of preparation:
February 2019

* Stemetil tablets and suppositories currently not available in New Zealand

stemetil-ccsiv4-cmiv13-08feb19

Published by MIMS April 2019

BRAND INFORMATION

Brand name

Stemetil

Active ingredient

Prochlorperazine

Schedule

S4

 

1 Name of Medicine

Stemetil tablets.

Prochlorperazine maleate.

Stemetil solution for injection.

Prochlorperazine mesilate.

Stemetil suppositories.

Prochlorperazine base.

2 Qualitative and Quantitative Composition

Stemetil tablets.

Each tablet contains 5 mg prochlorperazine maleate.

Excipients of known effect.

Wheat starch (gluten).

Stemetil injection ampoules.

Each 1 mL ampoule contains 12.5 mL prochlorperazine mesilate.

Excipients of known effect.

Sodium metabisulfite, sodium sulfite (sulfites).

Stemetil suppositories.

The suppositories come in two strengths, 5 mg or 25 mg. Each suppository contains 5 mg or 25 mg prochlorperazine maleate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Stemetil 5 mg tablets are off-white to pale cream coloured circular tablets, not more than slightly mottled or specked, one side impressed with 'S' and reverse face plain.
Stemetil 12.5 mg/mL solution for injection is clean, bright and not more than very pale yellow.
Stemetil suppositories contain prochlorperazine base equivalent to 5 mg and 25 mg prochlorperazine maleate. Stemetil suppositories are cream, smooth, torpedo-shaped suppositories.

4 Clinical Particulars

4.1 Therapeutic Indications

Nausea and vomiting due to various causes including migraine; vertigo due to Meniere's syndrome, labyrinthitis and other causes.

4.2 Dose and Method of Administration

Nausea and vomiting.

Adults.

If oral administration is not practical, a deep intramuscular injection of 1 mL (12.5 mg) or a 25 mg suppository should be used, followed, if required, by normal oral medication six hours later.
Do not use a darkened solution for injection (more than pale yellow).
Dosage should be adjusted to suit the response of the individual, beginning with lowest recommended dosage.

Oral.

5 or 10 mg two or three times daily.

Acute.

20 mg at once, followed, if necessary, by 10 mg two hours later.

Children.

(See Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
If it is considered unavoidable to use prochlorperazine for a child, the dosage is 250 microgram/kg bodyweight two or three times a day.
Prochlorperazine has been associated with dystonic reactions particularly after a cumulative dosage of 500 microgram/kg. It should, therefore, be used cautiously in children.
Prochlorperazine is not recommended for children weighing less than 10 kg and should not be given to children by the rectal or intramuscular route.
When treating children, it is recommended that the 5 mg tablets are used.

Vertigo and Meniere's disease.

Adults.

Oral.

5 to 10 mg three or four times daily.
Dosage may be reduced gradually after several weeks to a maintenance dosage of 5 to 10 mg daily.

Children.

Oral.

Dose, same as for nausea and vomiting.

Geriatric.

In general, dosages in the lower range are sufficient for most elderly patients. Since they are especially susceptible to hypotension and extrapyramidal reactions, such patients should be observed closely. Dosage should be increased more gradually in elderly patients.

Impaired liver function.

Since prochlorperazine is extensively metabolised by the liver, dosage reduction may be necessary.

4.3 Contraindications

Circulatory collapse, central nervous system depression (coma or drug intoxication), previous history of a hypersensitivity reaction (e.g. jaundice or blood dyscrasia) to phenothiazines, especially to prochlorperazine, bone marrow depression.

4.4 Special Warnings and Precautions for Use

Prochlorperazine should be avoided in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis and prostate hypertrophy. It should be avoided in patients with a history of narrow angle glaucoma or agranulocytosis.
As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia and requires immediate haematological investigation.
Prochlorperazine can cause photosensitisation, therefore patients should be advised to avoid exposure to direct sunlight during treatment.
To prevent skin sensitisation in those frequently handling preparations of phenothiazines, the greatest care must be taken to avoid contact of the drug with the skin.
In schizophrenia, the response to prochlorperazine treatment may be delayed. If treatment is withdrawn, the reoccurrence of symptoms may not become apparent for some time. Avoid concomitant treatment with other neuroleptics.

Hypotension.

The autonomic side effects of the piperazine derivatives are less troublesome than those of other phenothiazines, however care should be taken if prochlorperazine is used in the elderly or in patients undergoing surgery with spinal anaesthesia.
Postural hypotension with tachycardia as well as local pain or nodule formation may occur after intramuscular administration of prochlorperazine.

Epileptics.

Close monitoring is required in patients with epilepsy or a history of seizures, as phenothiazines may lower the seizure threshold. The occurrence of convulsive seizures necessitates the discontinuation of treatment.
Piperazine derivatives are also less epileptogenic than other phenothiazines, but care should still be exercised in epileptic patients.

Anticholinergic effects.

Prochlorperazine can cause problems due to anticholinergic effects, especially in the elderly (urinary difficulties, constipation and precipitation of acute narrow angle glaucoma), but to a lesser extent than with other phenothiazines.

Hypocalcaemia.

It appears from a study of 5 hypocalcaemic patients with hypoparathyroidism that such patients are prone to acute dystonic reactions with prochlorperazine.

Sedative effect.

Prochlorperazine may impair mental and physical activity, especially during the first few days of therapy. Patients should be warned about activities requiring alertness.

Antiemetic effects.

The antiemetic effects of prochlorperazine may mask signs of overdosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction, brain tumour.

Reye's syndrome.

The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g. Reye's syndrome or other encephalopathy. The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye's syndrome.

Hypothermia.

Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy.

Tardive dyskinesia.

Tardive dyskinesia may develop in patients on antipsychotic drugs. The disorder consists of repetitive involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements). The trunk and limbs are less frequently involved. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome.
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. The risk seems to be greater in elderly patients, especially females.
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 sought.
There is no known effective treatment for tardive dyskinesia. Antiparkinsonian agents usually do not alleviate symptoms. It is suggested that antipsychotic agents be discontinued if symptoms of tardive dyskinesia appear.

Neuroleptic malignant syndrome.

A potentially fatal syndrome called neuroleptic malignant syndrome has been reported in association with antipsychotic drugs. The syndrome is characterised by muscular rigidity, fever, hyperthermia, altered consciousness and autonomic instability (e.g. tachycardia, labile blood pressure, profuse sweating, dyspnoea).
It is imperative that prochlorperazine treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity).
Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and serve as early warning signs.
The management of neuroleptic malignant syndrome should include immediate discontinuation of anti-psychotic drugs, intensive monitoring and treatment of symptoms, and treatment of any associated medical problems.

QT interval.

Very rare cases of QT interval prolongation have been reported with prochlorperazine. Neuroleptic phenothiazines may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsades de pointes type, which is potentially fatal (sudden death).
QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalemia and congenital or acquired (i.e. drug induced) QT prolongation. If the clinical situation permits, medical and laboratory evaluations should be performed to rule out possible risk factors before initiating treatment with a neuroleptic agent and as deemed necessary during treatment (see Section 4.8 Adverse Effects (Undesirable Effects)).

Cerebrovascular events.

An increased risk of cerebrovascular events has been reported in elderly patients with dementia treated with atypical antipsychotic drugs. An increase in the risk of cerebrovascular events with other antipsychotic drugs or other populations of patients cannot be excluded. Prochlorperazine should, therefore, be used with caution in patients with stroke risk factors.

Thromboembolism.

Cases of venous thromboembolism (VTE), sometimes fatal, 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 Stemetil and preventative measures undertaken. Therefore, prochlorperazine should be used with caution in patients with risk factors for thromboembolism (see Section 4.8 Adverse Effects (Undesirable Effects)).

Hyperglycaemia.

Hyperglycaemia or intolerance to glucose has been reported in patients treated with prochlorperazine. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on prochlorperazine, should get appropriate glycaemic monitoring during treatment (see Section 4.8 Adverse Effects (Undesirable Effects)).

Injection.

Do not use a darkened solution for injection (more than pale yellow).
Postural hypotension with tachycardia as well as local pain or nodule formulation may occur after intramuscular administration.

Use in hepatic impairment.

Caution should be used in patients with existing liver disease due to the extensive hepatic metabolism of prochlorperazine. A past history of jaundice resulting from phenothiazine therapy indicates a hypersensitivity reaction and there is a likelihood of cross sensitivity to other phenothiazines.

Use in the elderly.

It should be used with caution in the elderly, particularly during very hot or very cold weather (risk of hyper-, hypothermia).
The elderly are particularly susceptible to postural hypotension, sedation and extrapyramidal side effects.
Stemetil should be used cautiously in the elderly owing to their susceptibility to drugs acting on the central nervous system and a lower initial dosage is recommended. There is an increased risk of drug-induced Parkinsonism in the elderly particularly after prolonged use. Care should also be taken not to confuse the adverse effects of Stemetil, e.g. orthostatic hypotension, with the effects due to the underlying disorder.

Elderly patients with dementia.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Although the causes of death in clinical trials with atypical antipsychotics 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.
Prolonged administration of any phenothiazine may result in persistent or tardive dyskinesias, particularly in the elderly and children.
Stemetil is not licensed for the treatment of dementia-related behavioural disturbances.

Paediatric use.

Prochlorperazine is not recommended for use in children less than 10 kg, or under 2 years of age as acute extrapyramidal reactions are more likely to occur.
Stemetil has been associated with dystonic reactions therefore, it should be used cautiously in children.
Prochlorperazine should not be given to children by the rectal or intramuscular route.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Adrenaline must not be used in patients overdosed with Stemetil.
Caution is required with the use of the following medicines due to the risk of QT prolongation (see Section 4.4 Special Warnings and Precautions for Use):
Class Ia antiarrhythmic agents such as quinidine and disopyramide.
Class III antiarrhythmic agents such as amiodarone and sotalol.
Other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, sparfloxacin.
Medicines which induce bradycardia, such as bradycardia-inducing calcium channel blockers (diltiazem, verapamil), beta-blockers, clonidine, guanfacine, digitalis.
Medicines which can cause hypokalaemia, such as diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, tetracosactides.
Other antipsychotics.
Prochlorperazine may enhance the CNS depressant effects of alcohol and other depressant drugs, and potentiate the anticholinergic effects of atropinic agents and tricyclic antidepressants. Respiratory depression may occur. Impaired vigilance may make it dangerous to drive or use machines. Avoid consumption of alcoholic beverages and medications containing alcohol.
The mild anticholinergic effect of prochlorperazine may be enhanced by other anticholinergic drugs, possibly leading to dry mouth, constipation, heat stroke, urinary retention and other adverse effects.
Some drugs interfere with absorption of prochlorperazine:
anti-Parkinson drugs;
lithium;
topical gastro-intestinal agents (magnesium, aluminium and calcium salts, oxides and hydroxides): Reduced gastro-intestinal absorption of prochlorperazine. Antacids should not be taken at the same time as prochlorperazine.
High doses of prochlorperazine reduce the response to hypoglycaemic agents.
The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by prochlorperazine.
The action of some drugs may be opposed by prochlorperazine; these include amfetamine, levodopa, clonidine, guanethidine, adrenaline.
Increases or decreases in the plasma concentrations of a number of drugs, e.g. propranolol, phenobarbital have been observed.
There is an increased risk of arrhythmias when prochlorperazine is used with concomitant QT prolonging drugs (including certain antiarrhythmics, antidepressants and other antipsychotics) and drugs causing electrolyte imbalance.
There is an increased risk of agranulocytosis when prochlorperazine is used concurrently with drugs with myelosuppressive potential, such as carbamazepine or certain antibiotics and cytotoxics.
In patients treated concurrently with prochlorperazine and lithium, there have been rare reports of neurotoxicity.
Phenothiazines are potent inhibitors of CYP2D6. Co-administration of phenothiazines with amitriptyline, a CYP2D6 substrate, may lead to an increase in the plasma levels of amitriptyline. Monitor patients for dose-dependent adverse reactions associated with amitriptyline.
Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce a transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.
Procarbazine has been reported to potentiate the extrapyramidal side effects encountered with the use of prochlorperazine. Phenothiazines have been reported both to impair and increase metabolism of phenytoin, with uncertain clinical significance. Patients on levodopa should not be given phenothiazines because the two drugs are physiologically antagonistic.
Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.
Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly.
Phenothiazines can diminish the effect of oral anticoagulants. Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs. Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
When given in high doses during late pregnancy, phenothiazines have caused jaundice, hyperreflexia, hyporeflexia or prolonged extrapyramidal disturbances in the child. There is evidence of harmful effects in animals. The following effects have been reported (in postmarketing surveillance) in neonates exposed to phenothiazines during the third trimester of pregnancy:
various degrees of respiratory disorders ranging from tachypnoea to respiratory distress, bradycardia and hypotonia, most often when other drugs such as psychotropic or antimuscarinic drugs were coadministered;
signs related to the atropinic properties of phenothiazines such as meconium ileus, delayed meconium passage, initial feeding difficulties, abdominal bloating, tachycardia;
neurological disorders such as extrapyramidal symptoms including tremor and hypertonia, somnolence, agitation.
Appropriate monitoring and treatment of neonate born to mothers receiving prochlorperazine is recommended.
Like other drugs it should be avoided in pregnancy unless the physician considers it essential. Prochlorperazine may occasionally prolong labour and at such a time should be withheld until the cervix is dilated 3-4 cm. Possible adverse effects on the foetus include lethargy or paradoxical hyperexcitability, tremor and a low Apgar score.
Trace amounts of another phenothiazine, chlorpromazine, have been detected in breast milk, but there is no information available for prochlorperazine. Consequently, it is not known whether it is excreted in breast milk or whether it has a harmful effect on the newborn.
Therefore, prochlorperazine is not recommended for nursing mothers unless the expected benefits outweigh any potential risk.

4.7 Effects on Ability to Drive and Use Machines

Prochlorperazine may impair mental and physical activity especially during the first few days of therapy. Patients should be warned about activities requiring alertness.

4.8 Adverse Effects (Undesirable Effects)

The following reactions have been reported for prochlorperazine or phenothiazines in general.

More common reactions.

Gastrointestinal.

Constipation, dry mouth.

Nervous system.

Drowsiness, akathisia, parkinsonism (with dyskinesia, tremor and rigidity).

Ocular.

Blurred vision.

Vascular.

Hypotension.

Less common reactions.

Biochemical abnormalities.

Elevated serum levels of bilirubin and hepatic enzymes may occur if the patient develops cholestatic jaundice.

Cardiovascular.

Peripheral oedema, cardiac arrhythmias, ECG changes, QT interval prolongation, ST depression, U-Wave and T-Wave changes. Cardiac arrhythmias, including ventricular arrhythmias and atrial arrhythmias, a-v block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest have been reported during phenothiazine therapy.
Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose patients to cardiac events. There have been isolated reports of sudden death, with possible causes of cardiac origin (see Section 4.4 Special Warnings and Precautions for Use), as well as cases of unexplained sudden death, in patients receiving neuroleptic phenothiazines.
Cases of venous thromboembolism, including cases of pulmonary embolism, sometimes fatal, and cases of deep vein thrombosis have been reported with antipsychotic drugs (see Section 4.4 Special Warnings and Precautions for Use).

Dermatological.

Dermatitis or contact dermatitis, maculopapular eruptions, erythema multiforme, urticaria, photosensitivity, abnormal pigmentation.

Endocrine.

Endocrine disturbances including elevated prolactin levels, hyperglycaemia, intolerance to glucose, hypoglycaemia, menstrual irregularities, galactorrhoea, gynaecomastia, amenorrhoea, impotence.

Gastrointestinal.

Paralytic ileus.

Genitourinary.

Urinary retention, priapism, inhibition of ejaculation.

Haematological.

Agranulocytosis, atypical lymphocytes, thrombocytopenia, leucopenia, aplastic anaemia.

Hepatic.

Jaundice, liver damage.

Nervous system.

Acute dystonia or dyskinesias including oculogyric crisis.
Tardive dyskinesia: It can even occur after treatment has been stopped.
Torticollis and opisthotonus and trismus, seizures, EEG changes, headache, insomnia, catatonia, hyperpyrexia, agitation, dizziness.
Cases of convulsions have been reported.

Ocular.

Pigmentary retinopathy.
Brownish deposits in the anterior segment of the eye, due to accumulation of the product.

Psychiatric.

Activation of psychotic symptoms.

Respiratory.

Respiratory depression, nasal stuffiness.

Metabolism and nutrition disorders.

Hyponatraemia and inappropriate antidiuretic hormone secretion have also been reported.
In post-marketing surveillance cases of hyperglycaemia or intolerance to glucose have been reported with antipsychotic phenothiazines (see Section 4.4 Special Warnings and Precautions for Use).

Immune system disorders.

Hypersensitivity reactions such as angioedema and urticaria have been reported.

General disorders and administration site conditions.

Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness).

Pregnancy, puerperium and perinatal conditions.

Drug withdrawal syndrome neonatal (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Serious or life threatening reactions.

Prochlorperazine can cause very serious acute dystonic reactions in children leading to cyanosis from laryngospasm, apnoea requiring artificial ventilation, life threatening tetanus like syndromes, coma and even death. These reactions can occur with a single therapeutic dose. For treatment, see Section 4.9 Overdose. Also, long-term phenothiazine therapy has been associated with ECG changes and life threatening cardiac arrhythmias.

Reporting suspected adverse reactions.

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 www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

Symptoms.

Overdosage with phenothiazines may cause CNS depression progressing from drowsiness to coma with areflexia. Patients with early or mild intoxication may experience restlessness, confusion and excitement.
Other symptoms include hypotension, tachycardia, hypothermia, pupillary constriction, restlessness, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden apnoea. There is no information available regarding lethal dose in man.
High doses cause depression of the central nervous system, presenting as lethargy, dysartria, ataxia, stupor, reduction in consciousness into coma, convulsions; mydriasis; cardiovascular symptoms (related to risk of QT interval prolongation), such as hypotension, ventricular tachycardia and arrhythmia; respiratory depression; hypothermia. These effects may be potentiated by other medicines or by alcohol. Anticholinergic syndrome is of importance.
Extremely serious parkinsonian syndrome may occur.

Treatment.

Acute dystonic reactions.

Intramuscular benztropine (or another antiparkinsonian agent) should be given immediately (adults: 1 to 2 mg i.m., children: 0.2 mg i.m. initially, with increments if necessary).

Overdosage.

Emesis should not be induced, not only because the antiemetic action of prochlorperazine prevents the effect of the emetic agent, but also because the sedative and extra-pyramidal side effects increase the risk of pulmonary aspiration should vomiting occur. Management is generally supportive with particular attention to the possibility of obstructed ventilation, severe hypotension, hypothermia, cardiac arrhythmias, convulsions and prolonged deep sedation. Acute dystonic reactions usually occur early (if at all); treatment is with anticholinergic agents, as above.
Adrenaline must not be used as it may cause a paradoxical further lowering of blood pressure.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia) or the National Poisons Centre on 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Prochlorperazine is a phenothiazine with a piperazine moiety in the side chain. It possesses strong antiemetic and antipsychotic activity with less sedative action than chlorpromazine.

Mechanism of action.

As with other phenothiazines, prochlorperazine has actions on several neurotransmitter systems:
1. Antidopamine action, which probably contributes to both the therapeutic effect and unwanted effects including extrapyramidal disorders and endocrine disturbances.
2. α-Adrenoreceptor antagonism, which contributes to cardiovascular side effects such as orthostatic hypotension and reflex tachycardia.
3. Potentiation of noradrenaline by blocking its reuptake into nerve terminals.
4. Weak anticholinergic action.
5. Weak antihistamine action.
6. Weak serotonin antagonism.
Prochlorperazine also has an effect on temperature control and blocks conditioned avoidance responses.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

There are few published data on prochlorperazine pharmacokinetics in the human. Most studies have been done in rats and dose levels do not correspond to those used clinically and metabolic pathways may differ. Similar overall pharmacokinetic patterns however would occur in the human.

Absorption.

Prochlorperazine is well absorbed from the GI tract in rats but absorption is slowed in repeatedly treated animals.

Distribution.

The drug is widely distributed to tissues including the brain, fat, kidney, heart and skin and is stored in reticuloendothelial tissues.

Metabolism.

Phenothiazines are metabolised primarily in the liver and are subject to enterohepatic circulation.

Excretion.

Excretion is mainly in the faeces. Only a very small amount (approx. 0.1%) of prochlorperazine and its metabolites are excreted in the first 24 hours in the urine and the drug may continue to be excreted in the urine for up to 3 weeks after cessation of long term therapy. The elimination half-life is approximately 24 hours, presumably due to its enterohepatic circulation.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Tablets.

Calcium hydrogen phosphate dihydrate, magnesium stearate, sodium lauryl sulfate, wheat starch.

Solution for injection.

Monoethanolamine, sodium chloride, sodium metabisulfite, sodium sulfite, water for injection.

Suppositories.

Hard fat.

6.2 Incompatibilities

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

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Tablets.

Store below 30°C. Protect from light.

Suppositories.

Store below 25°C. Protect from light.

Solution for injection.

Store below 25°C. Protect from light. Keep ampoules and trays in the carton until time of use.

6.5 Nature and Contents of Container

Stemetil tablets are available in blister packs of 25, 100* and 250* tablets.
Stemetil injection ampoules are available in cartons of 10 ampoules. Each ampoule contains 1 mL.
Stemetil suppositories are available in blister packs of 5 suppositories*.
* Not marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


Prochlorperazine is 2 chloro-10-(3-(4-methyl piperazinyl)-propyl) phenothiazine. Prochlorperazine maleate contains 62% of the active base; prochlorperazine mesilate contains 66% of the active base.
The maleate is an odourless, nonhydroscopic, white or almost white, fine granular powder, which becomes coloured on exposure to light. It is sparingly soluble (about 0.1%) in water, ethanol or methanol and is insoluble in ether or chloroform.
The mesilate is an odourless, nonhydroscopic, almost white, crystalline solid which becomes coloured on exposure to light. It is very soluble in water (more than 2 g/mL) but is only slightly soluble in ethanol or chloroform and is insoluble in ether or benzene. The pH of a 2% aqueous solution is between 2 and 3.

Tablets.


Molecular formula: C20H24ClN3S.2C4H4O4.

Injection.


Molecular formula: C20H24ClN3S.2CH3SO3H.

Suppositories.


Molecular formula: C20H24ClN3S.

CAS number.

Tablets.

84-02-6.

Injection.

5132-55-8.

Suppositories.

58-38-8.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes