Consumer medicine information

Nausetil Tablets

Prochlorperazine maleate

BRAND INFORMATION

Brand name

Nausetil

Active ingredient

Prochlorperazine maleate

Schedule

What is in this leaflet

This leaflet answers some common questions about Nausetil. 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 or pharmacist has weighed the risks of you taking Nausetil 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 NAUSETIL is used for

Nausetil contains the active ingredient prochlorperazine maleate and is used to treat nausea associated with migraine (severe headache).

Nausetil belongs to a group of medicines called phenothiazines, which help 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.

There is no evidence that it is addictive.

Before you take it

When you must not take it

Do not take Nausetil if you have ever had an allergic reaction to:

prochlorperazine maleate
the group of medicines called phenothiazines
any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include asthma, wheezing, shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, skin rash, itching or hives.

Do not take Nausetil if you have any of the following medical conditions:

shock
disease of the blood with a low number of blood cells
jaundice, yellowing of the skin and/or eyes.

Nausetil 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 Nausetil.

Do not give Nausetil to children under the age of two (2) years or under 10 kg in weight.

Do not take it after the expiry date (EXP) printed on the pack.

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

Talk to your doctor or pharmacist if you are not sure whether you should start taking Nausetil.

Before you start to take it

Tell your doctor or pharmacist if you are allergic to any other medicines or any foods, dyes or preservatives.

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

Tell your doctor or pharmacist if you are breastfeeding or plan to breastfeed. It is not recommended to take Nausetil while breastfeeding as it is not known whether it 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
epilepsy, seizures or fits
low blood calcium levels
an underactive thyroid gland
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 (especially in the elderly)
high blood sugar levels.

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 Nausetil.

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 may be affected by Nausetil or may affect how well it works. You may need to take different amounts of your medicines or you may need to take different medicines. Your doctor or pharmacist has a more complete list of medicines to avoid while taking Nausetil. These include:

some medicines used to control depression or mood swings
alcohol
desferrioxamine, a drug used in iron overdose
procarbazine, an anticancer drug
some medicines used to control epilepsy
medicines used to treat Parkinson's disease
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
medicines that prevent blood clotting
medicines used to treat high blood pressure and fluid build-up in your body
bepridil, cisapride, sultopride, thioridazine, methadone, erythromycin injection, vincamine injection, halofantrine, pentamidine, sparfloxacin, amphotericin B injection, glucocorticoids, tetracosactides
certain laxatives.

How to take it

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

How much to take

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

For adults, the usual recommended dose is 1 or 2 tablets two to three times daily. For acute treatment, 4 tablets at once, followed if necessary by 2 tablets two hours later, may be taken.

Children (over the age of two (2) years or over 10 kg), the elderly or patients who have a pre-existing liver condition may need to take fewer tablets.

How to take it

Swallow the tablet whole with a full glass of water.

Do not chew the tablet.

When to take it

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

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) for advice, or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Nausetil. 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
fast heart beat
decrease in body temperature
small pupils in the eye
difficulty in swallowing or breathing
blue skin.

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 Nausetil.

The condition is more likely to occur during long term treatment, 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 Nausetil.

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

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

Tell your doctor or pharmacist immediately if you become pregnant while taking Nausetil.

Things you must not do

Do not give Nausetil to children under the age of two (2) years or under 10 kg in weight.

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

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

Things to be careful of

Be careful driving or operating machinery until you know how Nausetil affects you. As with other medicines, Nausetil may cause dizziness, light-headedness, tiredness and drowsiness in some people, especially in the first few days of treatment.

If Nausetil makes you feel light-headed, dizzy or faint, get up slowly from a sitting or lying position.

Be careful when drinking alcohol while taking Nausetil. If you drink alcohol, dizziness or light-headedness may be worse.

Your doctor or pharmacist may suggest you avoid alcohol while you are being treated with Nausetil.

If outdoors, wear protective clothing and use at least a 15+ sunscreen. Nausetil 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.

Make sure you keep cool in hot weather and keep warm in cool weather. Nausetil 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 Nausetil. Nausetil helps most people with nausea associated with migraine, 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.

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

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

constipation
dry mouth
drowsiness
restlessness
trembling, rigid posture, mask-like face, slow movements and a shuffling unbalanced walk
twitching
blurred vision.

The following side effects are less common:

dizziness, light-headedness
changes in heart beat
swelling of the hands, ankles or feet
itchy skin rash
for females: unusual secretion of breast milk, irregular periods
for males: breast enlargement, difficulty in ejaculating
severe pain in the stomach with bloating, gut cramps and vomiting
difficulty passing urine
yellowing of the skin and/or eyes
headache
insomnia
seizures
difficulty in breathing
frequent infections such as fever, severe chills, sore throat or mouth ulcers
bleeding or bruising more easily than normal
excessive thirst
dry mouth and skin
changes in vision.

If any of the following happen, go to Accident and Emergency at your nearest hospital:

unusual muscle tone or spasms causing distortion of the body in children
chest pain and shortness of breath.

These are very serious side effects. Serious side effects are rare.

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

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

After taking it

Storage

Keep your tablets in a cool dry place, protected from light where the temperature stays below 30°C.

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the blister they may not keep as well.

Keep it where young 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

Return any unused medicine to your pharmacist.

Product Description

What it looks like

Nausetil tablets are round, pale yellow tablets engraved with "M" on one side and plain on the other. They are available in packs of 10 tablets.

Ingredients

Active ingredient:
Each tablet contains 5 mg of prochlorperazine maleate.

Inactive ingredients:

wheat starch
calcium hydrogen phosphate
magnesium stearate
sodium lauryl sulfate
quinoline yellow.

Nausetil tablets do not contain sucrose or lactose.

Sponsor

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

Australian Registration Number:
AUST R 159537

This leaflet was prepared in June 2010.

Published by MIMS July 2024

BRAND INFORMATION

Brand name

Nausetil

Active ingredient

Prochlorperazine maleate

Schedule

1 Name of Medicine

Prochlorperazine maleate.

2 Qualitative and Quantitative Composition

Each Nausetil tablet contains 5 mg of prochlorperazine maleate as the active ingredient.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Nausetil 5 mg tablets are round, biconvex and pale yellow engraved with "M" on one side and plain on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of nausea associated with migraine.

4.2 Dose and Method of Administration

Adults.

The recommended dosage is 5 or 10 mg two or three times daily.
For acute treatment, 20 mg at once, followed, if necessary, by 10 mg two hours later.

Children.

Do not use in children and adolescents under 18 years of age.

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 (CNS) 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.
Hypersensitivity to prochlorperazine, other phenothiazines, or to any of the other ingredients of Nausetil.
In children, due to a possible association between use of phenothiazine containing products and Sudden Infant Death Syndrome (SIDS).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Migraine should be medically diagnosed prior to first use of this product.
Nausetil should be avoided in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, phaeochromocytoma, myasthenia gravis, prostatic hypertrophy. It should be avoided in patients with a history of narrow angle glaucoma or agranulocytosis.
Acute withdrawal symptoms, including nausea, vomiting, headache, anxiety, agitation, dyskinesia, dystonia, disturbed temperature regulation, and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics. Relapse may also occur, and the emergence of extrapyramidal reactions has been reported. Therefore, gradual withdrawal is advisable. Symptoms of withdrawal can occur following treatment at any dose. Withdrawal of treatment should occur under close medical supervision.
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.
All patients should be advised that, if they experience fever, sore throat or any other infection, they should inform their physician immediately and undergo a complete blood count. Treatment should be discontinued if any marked changes (hyperleukocytosis, granulocytopenia) are observed in the blood count.
As with all antipsychotic drugs, prochlorperazine should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat those conditions in which depression and psychosis coexist.
Prochlorperazine can cause photosensitisation, therefore patients should be advised to avoid exposure to direct sunlight during treatment.
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.
Phenothiazines may be additive with, or may potentiate the action of, other CNS depressants such as opiates or other analgesics, barbiturates or other sedatives, general anesthetics, or alcohol.

Stroke.

In randomised clinical trials versus placebo performed in a population with elderly patients with dementia and treated with certain atypical antipsychotic drugs, an increase of the risk of cerebrovascular events has been observed. The mechanism of such risk increase is not known. An increase in the risk with other antipsychotic drugs or other populations of patients cannot be excluded. Prochlorperazine should be used with caution with stroke risk factors.

Hypotension.

The autonomic side effects of the piperazine derivatives are less troublesome than those of other phenothiazines, however care should be taken if Nausetil 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 five 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, e.g. intestinal obstruction and brain tumour.

Reye's syndrome.

The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the CNS 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. Although neuroleptic malignant syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors (see Section 4.8 Adverse Effects (Undesirable Effects)).
The management of neuroleptic malignant syndrome should include immediate discontinuation of antipsychotic drugs, intensive monitoring and treatment of symptoms and treatment of any associated medical problems.

QT intervals.

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, hypokalaemia 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. Nausetil should, therefore, be used with caution in patients with stroke risk factors.

Thromboembolism.

Cases of venous thromboembolism, 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 Nausetil and preventative measures undertaken. Therefore, Nausetil 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 Nausetil. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on Nausetil, should get appropriate glycaemic monitoring during treatment (see Section 4.8 Adverse Effects (Undesirable Effects)).

Alcohol use.

Patients are strongly advised not to consume alcohol and alcohol containing medicines while being treated with prochlorperazine.

Hypersensitivity reactions.

Hypersensitivity reactions including anaphylaxis, urticaria and angioedema have been reported with prochlorperazine use. In case of allergic reactions, treatment with prochlorperazine must be discontinued and appropriate symptomatic treatment initiated (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 renal impairment.

No data available.

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).
Nausetil 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 Nausetil, 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.
Careful monitoring of treatment with prochlorperazine is required when administered in elderly patients exhibiting greater susceptibility to orthostatic hypotension, sedation, and extrapyramidal effects; chronic constipation (risk of ileus paralytic); possible prostatic hypertrophy.

Paediatric use.

The medicine should not be given to children and adolescents under 18 years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Contraindicated combinations.

Dopaminergics, except in patients with Parkinson's disease.
Mutual antagonism between dopaminergics and neuroleptics.
Where treatment for neuroleptic-induced extrapyramidal symptoms is required, anticholinergic antiparkinsonian agents should be used in preference to levodopa, since neuroleptics antagonise the antiparkinsonian action of dopaminergics.
Adrenaline must not be used in patients overdosed with Nausetil (see Section 4.9 Overdose).

Combinations not recommended or requiring precaution.

Dopaminergics in patients with Parkinson's disease.
Dopaminergics may cause or exacerbate psychotic disorders. If treatment with neuroleptics is required in patients with Parkinson's disease treated with a dopaminergic, the latter should be tapered off gradually (sudden discontinuation of dopaminergic agents exposes the patient to a risk of "neuroleptic malignant syndrome"). For parkinsonian patients who require treatment with both a neuroleptic and a dopaminergic agent, use the minimum effective doses of both medications.
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 (tetracosactrin).
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.
Anticholinergic agents may reduce the antipsychotic effect of neuroleptics. 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.
Gastro-intestinal agents that are not absorbed (magnesium, aluminium and calcium salts, oxides and hydroxides): reduced gastro-intestinal absorption of phenothiazine neuroleptics may occur. Such gastro-intestinal agents should not be taken at the same time as prochlorperazine.
High doses of prochlorperazine reduce the response to hypoglycaemic agents, the dosage of which might have to be raised.
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.

Cytochrome P450 2D6 metabolism.

Some phenothiazines are moderate inhibitors of CYP2D6. There is a possible pharmacokinetic interaction between inhibitors of CYP2D6, such as phenothiazines and CYP2D6 substrates. 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.
Nausetil should be avoided in patients taking monoamine oxidase inhibitors.
Because of convulsive risk, the combined use of medicinal products which lower the seizure threshold should be carefully assessed.
Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce a transient metabolic encephalopathy characterised by loss of consciousness for 48 to 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 and 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)
The use of Nausetil is not recommended during pregnancy and in women of childbearing potential not using contraception, unless the potential benefits outweigh the potential risks.
Data from epidemiological studies cannot exclude the risk of congenital malformations in children exposed in utero to prochlorperazine.
When given in high doses during late pregnancy, phenothiazines have caused jaundice, hyper-reflexia, hyporeflexia or prolonged extrapyramidal disturbances in the child. There is inadequate evidence of the safety of Nausetil in human pregnancy, but it has been widely used for many years without apparent ill consequence. 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 doctor considers it essential.
Prochlorperazine may occasionally prolong labour, and at such a time should be withheld until the cervix is dilated 3 to 4 cm. Possible adverse effects on the foetus include lethargy or paradoxical hyperexcitability, tremor and a low Apgar score.
Phenothiazines may be excreted in milk, therefore, breastfeeding is not recommended during treatment with prochlorperazine.
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 nor whether it has a harmful effect on the newborn infant.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about drowsiness and advised not to drive or operate machinery, particularly during the early days of treatment, until they know how Nausetil affects them. Prochlorperazine may impair mental and physical activity, especially during the first few days of therapy. Patients should be warned about drowsiness and advised not to drive or operate machinery particularly during the early days of treatment, until they know how Nausetil affects them.

4.8 Adverse Effects (Undesirable Effects)

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

Vascular disorders.

More common: Orthostatic hypotension. Elderly or volume depleted patients are particularly susceptible; it is more likely to occur after intramuscular injection.
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).

Blood and lymphatic system disorders.

Not known: Eosinophilia.
Less common: Agranulocytosis, atypical lymphocytes, thrombocytopenia, leucopenia, aplastic anaemia.

Biochemical abnormalities.

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

Cardiac disorders.

Less common: Peripheral oedema, cardiac arrhythmias, electrocardiographic (ECG) changes, QT interval prolongation, ST depression, U-Wave and T-Wave changes. Cardiac arrhythmias, including ventricular arrhythmias and atrial arrhythmias, atrioventricular block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest have been reported during phenothiazine therapy, possibly related to dosage.
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.
Not known: Torsades de pointes.

Skin and subcutaneous disorders.

Less common: Dermatitis allergic, maculopapular eruptions, erythema multiforme, urticaria, photosensitivity reaction, pigmentation disorder.

Endocrine disorders.

Less common: Endocrine disturbances including elevated prolactin levels, hyperglycaemia, intolerance to glucose, hypoglycaemia, menstrual irregularities, galactorrhoea, gynaecomastia, amenorrhoea, erectile dysfunction.
Not known: Temperature regulation disorder.

Gastrointestinal.

More common: Constipation, dry mouth.
Less common: Paralytic ileus.

Renal and urinary disorders.

Less common: Urinary retention.

Hepatobiliary disorders.

Less common: Jaundice cholestatic, liver damage.

Nervous system disorders.

More common: Drowsiness, akathisia, parkinsonism (with dyskinesia, tremor and rigidity).
Less common: Dystonia including oculogyric crisis usually transitory are commoner in children and young adults, and usually occur after dosage increases.
Less common: Tardive dyskinesia: If this occurs it is usually, but not necessarily, after prolonged or high dosage.
It can even occur after treatment has been stopped. Dosage should therefore be kept low whenever possible.
Less common: Torticollis and opisthotonus and trismus, seizures, electroencephalographic (EEG) changes, headache, insomnia, catatonia, hyperpyrexia, agitation, dizziness.
Less common: Seizures have been reported.
Not known: Anticholinergic effects such as ileus paralytic, risk of urinary retention, dry mouth, constipation, accommodation disorder.
Not known: Extrapyramidal syndrome:
Akinesia with or without hypertonia, partially relieved by anticholinergic antiparkinsonian agents.
Hyperkinetic-hypertonic movements, motor excitation.
Akathisia.
Not known: Insomnia.
Not known: Dizziness.
Not known: Sedation or somnolence.
Not known: Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur with any neuroleptic (see Section 4.4 Special Warnings and Precautions for Use).

Eye disorders.

More common: Blurred vision.
Less common: Pigmentary retinopathy.
Less common: Corneal deposits (brownish deposits in the anterior segment of the eye, due to accumulation of the drug and generally without effect on vision).
Not known: Accommodation disorder.

Psychiatric disorders.

Less common: Activation of psychotic symptoms.
Not known: Agitation, confusional state, delirium, anxiety.

Respiratory, thoracic and mediastinal disorders.

Less common: Respiratory depression, nasal congestion.

Metabolism and nutrition disorders.

Less common: 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.

Less common: Hypersensitivity reactions such as angioedema and urticaria have been reported.
Less common: Anaphylactic reaction.

Reproductive system and breast disorders.

Less common: Priapism, ejaculation disorder.

Pregnancy, puerperium and perinatal conditions.

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

Investigations.

Not known: Weight increased, liver function test abnormal.

Serious or life-threatening reactions.

Prochlorperazine is not recommended for use in children for the treatment of nausea associated with migraine.
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 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 www.tga.gov.au/reporting-problems.

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 humans.
High doses cause depression of the central nervous system, presenting as lethargy, dysarthria, 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.

In the event of overdose of Nausetil, take all appropriate measures immediately.

Acute dystonic reactions.

Intramuscular benztropine (or another antiparkinsonian agent) should be given immediately (adults: 1 to 2 mg intramuscularly; children: 0.2 mg intramuscularly 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 extrapyramidal side effects increase the risk of pulmonary aspiration should vomiting occur. Gastric lavage may be useful even several hours after the drug has been ingested since prochlorperazine reduces gastric motility. 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 Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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.

Pharmacology.

As with other phenothiazines, prochlorperazine has actions on several neurotransmitter systems as follows:
Antidopamine action, which probably contributes to both the therapeutic effect and unwanted effects including extrapyramidal disorders and endocrine disturbances.
Alpha-adrenoreceptor antagonism, which contributes to cardiovascular side effects, e.g. orthostatic hypotension and reflex tachycardia.
Potentiation of noradrenaline by blocking its reuptake into nerve terminals.
Weak anticholinergic action.
Weak antihistamine action.
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 gastrointestinal (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 (approximately 0.1%) of prochlorperazine and its metabolites is excreted in the first 24 hours in the urine and the drug may continue to be excreted in the urine for up to three 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

Excipients include wheat starch, magnesium stearate, sodium lauryl sulfate, calcium hydrogen phosphate anhydrous and quinoline yellow.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. Please see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

PVC/Al Blister pack available in packs of 10 tablets.

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.

CAS number.

84-02-6.
Chemical name: 2-chloro-10-[3-(4-methylpiperazin-1-yl) propyl]-10H-phenothiazine bis[hydrogen (Z)-butenedioate].
Chemical formula: C₂₀H₂₄ClN₃S, 2C₄H₄O₄.
Molecular weight: 606.2.
Prochlorperazine maleate is an odourless, nonhygroscopic, white or almost white, fine granular powder, which becomes coloured on exposure to light. It is very slightly soluble (about 0.1%) in water, ethanol or methanol and is insoluble in ether or chloroform.

7 Medicine Schedule (Poisons Standard)

S3 (Pharmacist Only Medicine).

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Nausetil Tablets

Prochlorperazine maleate

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Nausetil 5 mg Tablets