Consumer medicine information

Pramin

Metoclopramide hydrochloride

BRAND INFORMATION

Brand name

Pramin

Active ingredient

Metoclopramide hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pramin.

What is in this leaflet

This leaflet answers some common questions about PRAMIN.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking PRAMIN against the benefits they expect it will have for you.

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

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

What PRAMIN is used for

In Adults over 20 years, PRAMIN is used to:

  • control nausea and vomiting associated with using other medicines, kidney disease, radiation or chemotherapy treatment, cancer, childbirth, infectious diseases, or surgery
  • in the management of certain stomach problems associated with diabetes
  • with X-ray examinations of the stomach and/or intestines
  • activate stomach contractions in conditions where there is a need to encourage normal passage of food through the stomach and intestines
  • help with passing tubes into the intestines

In young adults and children over 1 year of age this medicine is used to

  • treat severe vomiting of known cause or following chemotherapy or radiation treatment
  • help with passing tubes into the intestine

PRAMIN belongs to a group of medicines called anti-emetics and is thought to work by blocking the action of a chemical in the brain which causes nausea and vomiting. It also increases the muscle contractions in the stomach and small intestine.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

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

There is no evidence that PRAMIN is addictive.

Before you take PRAMIN

When you must not take it

Do not take PRAMIN if you are allergic to medicines containing metoclopramide hydrochloride or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • skin rash, itching or hives on the skin

Do not take PRAMIN if you have any of the following:

  • active bleeding from the stomach and/or digestive tract
  • blockage of the stomach and/or digestive tract
  • recent surgery of the stomach and/or digestive tract
  • phaeochromocytoma (an adrenaline-producing tumour of the adrenal gland)
  • epilepsy (fits or convulsions)
  • take other medicines likely to cause extrapyramidal effects, such as antipsychotics/neuroleptics and certain antidepressants that can cause movement disorders. This reaction may include trembling and a sudden onset of uncontrollable muscle spasms affecting the eyes, head, neck and body.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking this medicine during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. PRAMIN passes into breast milk and can affect the flow of your breast milk. Your doctor will discuss the risks and benefits of taking this medicine when breastfeeding.

Tell your doctor if you have or have had any of the following medical conditions:

  • breast cancer
  • liver or kidney problems
  • Parkinson's disease - a condition affecting muscle control and movement
  • depression
    high blood pressure

Your doctor may want to take special care if you have any of these conditions.

If you have not told your doctor about any of the above, tell him/her before you start taking PRAMIN.

Taking other medicines

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

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

  • certain medicines used to treat mental disorders, including lithium, thioridazine
  • pain relievers such as codeine, morphine and paracetamol
  • atropine-like medicines used to prevent travel sickness and for stomach cramps
  • medicines used to relieve anxiety and/or help you sleep
  • levodopa, a medicine used in the treatment of Parkinson's disease
  • digoxin, a medicine used to treat heart failure
  • tetracycline, an antibiotic
  • ciclosporin, a medicine used to help prevent organ transplant rejection
  • monoamine oxidase inhibitors, a group of medicines used to treat depression.

These medicines may be affected by PRAMIN or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

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

How to take PRAMIN

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 may advise you to take a different dose. This depends on your condition and whether or not you are taking any other medicines.

The dose varies with the age of the patient and reason for use.

The total daily dosage of PRAMIN, especially for children and young adults, should not normally exceed 0.5mg/kg bodyweight or 30mg daily.

Space the doses as evenly as possible throughout the day.

20 + years: 1 tablet every 8 hours

15 to 20 years: ½ to 1 tablet every 8 hours

Children and young adults are very sensitive to the effects of PRAMIN. Your doctor will normally start the treatment at the lower dose. Do not exceed the prescribed dose in these age groups.

How to take it

Swallow the tablets with a full glass of water.

The tablets can be broken in half (along the break line).

Do not exceed the prescribed dose.

When to take it

PRAMIN is best taken 30 minutes before symptoms are likely to occur or 30 minutes before meals. Space the doses of PRAMIN evenly throughout the day.

Your doctor may tell you to take PRAMIN only when required for each occasion of nausea or vomiting.

How long to take it for

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

If you forget to take it

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

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of getting an unwanted side effect.

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.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much PRAMIN. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much PRAMIN, you may experience drowsiness, dizziness, agitation, headache, nausea, vomiting, and unusual movements, such as trembling and shaking of the hands and feet, and uncontrolled movements of the tongue, mouth or jaw.

While you are taking PRAMIN

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking PRAMIN.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you plan to have surgery, including dental surgery, tell your surgeon, anaesthetist or dentist that you are taking PRAMIN.

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

If you need to have any liver function tests or other tests, tell your doctor. PRAMIN may affect the results of some tests.

If your symptoms do not improve or if they become worse, tell your doctor.

Things you must not do

Do not use PRAMIN to treat any other complaints unless your doctor tells you to.

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

Things to be careful of

Be careful driving or operating machinery until you know how PRAMIN affects you. PRAMIN may cause drowsiness, dizziness or lightheadedness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous. Children should be careful when riding bicycles or climbing trees.

Be careful when drinking alcohol while taking PRAMIN. Combining PRAMIN and alcohol can make you more sleepy.

Side effects

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

Like all other medicines, PRAMIN may have unwanted side effects in some people. 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.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

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

  • drowsiness
  • fatigue, tiredness
  • anxiety, restlessness, agitation
  • trouble sleeping
  • diarrhoea, constipation, bowel irregularities
  • headache, dizziness
  • breast enlargement, unusual secretion of breast milk.

The above list includes the more common or mild side effects of PRAMIN.

Tell your doctor as soon as possible if you notice any of the following:

  • uncontrolled and repeated movements of the face, jaw or tongue, arms or legs. This may be a sign of tardive dyskinesia, a movement disorder which can be potentially irreversible
  • yellowing of the skin or eyes
  • fast or irregular heart beat
  • swelling of hands, ankles or feet.

The above list includes serious side effects which may require medical attention. Serious side effects are rare.

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

  • symptoms of an allergic reaction such as, skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath
  • sudden uncontrolled muscle spasms, stiffness of the arms or legs, muscle spasms of the face, locked jaw or upturned eyes
  • trembling of the hands or legs, slowing of all movements, shuffling walk
  • a sudden increase in body temperature, extremely high blood pressure, stiff muscles and severe convulsions. These could be signs of a serious side effect called neuroleptic malignant syndrome.

These are rare yet serious side effects and may need urgent medical attention.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some patients.

After taking PRAMIN

Storage

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

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

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

Keep PRAMIN 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 tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

PRAMIN is a white, normal convex tablet marked "ME" over "10" on one side and "G" on the reverse.

Available in bottles of 100 tablets or blister packs of 25 tablets.

Ingredients

The active ingredient in PRAMIN is metoclopramide hydrochloride monohydrate. Each PRAMIN tablet contains 10 mg of metoclopramide hydrochloride.

The tablets also contain:

  • lactose anhydrous
  • pregelatinised maize starch
  • microcrystalline cellulose
  • colloidal anhydrous silica
  • magnesium stearate.

PRAMIN tablets contain sugars as lactose and trace amounts of sulfites.

Supplier

PRAMIN is supplied in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

Australian registration numbers:
PRAMIN bottle - AUST R 17661
PRAMIN blister - AUST R 364450

This leaflet was prepared in November 2023.

PRAMIN_cmi\Nov23/00

Published by MIMS January 2024

BRAND INFORMATION

Brand name

Pramin

Active ingredient

Metoclopramide hydrochloride

Schedule

S4

 

1 Name of Medicine

Metoclopramide hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Each Pramin tablet contains metoclopramide hydrochloride monohydrate as the active ingredient, equivalent to 10 mg of metoclopramide hydrochloride.

Excipients with known effect.

Contains sugars as lactose and trace amounts of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Pramin 10 mg tablet.

White, normal convex, marked "ME" over "10" on one side, G on reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults (20 years and over).

As an adjunct to X-ray examination of the stomach and duodenum.
To assist in intestinal intubation.
To control nausea and vomiting associated with the following conditions: intolerance to essential drugs possessing emetic properties (such as cytotoxic agents); uraemia; radiation sickness; malignant disease; postoperative vomiting; labour; infectious diseases. There is no clear benefit in motion sickness or other labyrinth disturbances.
Pramin has been found useful in the management of gastric retention after gastric surgery; of diabetic gastroparesis of mild to moderate severity. Once control of diabetes is established by diet and/or insulin, use of metoclopramide should be discontinued.

Young adults and children over 1 year of age.

The use of Pramin in patients under 20 years should be restricted to the following situations and only be used as second line therapy.
Severe intractable vomiting of known cause.
Vomiting associated with radiotherapy and intolerance to cytotoxic drugs.
As an aid to gastrointestinal intubation.

4.2 Dose and Method of Administration

Patients with normal renal and hepatic function.

The dosage recommendations given below should be strictly adhered to if side effects of the dystonic type are to be avoided. Total daily dosage of metoclopramide, especially for children and young adults should not normally exceed 0.5 mg/kg bodyweight with a maximum of 30 mg daily. Metoclopramide should only be used after careful examination to avoid masking an underlying disorder, e.g. cerebral irritation. Maximum recommended treatment duration is 5 days in all age groups.

Medical indications.

Oral.

Usual adult (over 20 years) dose.

Maximum of 10 mg three times daily.

Elderly patients.

As for adults. To avoid adverse reactions, adhere strictly to dosage recommendations. When prolonged therapy is considered necessary, patients should be regularly reviewed.

Young adults and children over 1 year of age.

Tablets should not be used in children less than 15 years: treatment of children and young adults should commence at the lower dosage, where stated and used as second line therapy only.

Young adults 15-20 years.

5 to 10 mg three times daily, commencing at the lower dosage.

Children 5-14 years.

2.5 to 5 mg three times daily.

Children 3-5 years.

2 mg two to three times daily.

Children 1-3 years.

1 mg two or three times daily.

Diagnostic indications.

A single dose of metoclopramide may be given 5 to 10 minutes before examination. Subject to bodyweight considerations, the following dosages are recommended:

Adults 20 years and over.

10 to 20 mg.

Young adults 15-19 years.

10 mg.

Children 9-14 years.

5 mg.

Children 5-9 years.

2.5 mg.

Children 3-5 years.

2 mg.

Children 1-3 years.

1 mg.

Patients with impaired renal or hepatic function.

In patients with clinically significant degrees of renal or hepatic impairment, clearance of Pramin is likely to be reduced. It is suggested that therapy be initiated at half the recommended dose. Subsequent dosage will depend on individual clinical response.

4.3 Contraindications

Cases in which gastrointestinal stimulation might be dangerous, e.g. in the presence of gastrointestinal haemorrhage, mechanical obstruction, or perforation.
Phaeochromocytoma. Hypertensive crises have been reported in three patients with this tumour who have been given metoclopramide, probably due to the release of catecholamines from the tumour. Such hypertensive crises may be controlled by phentolamine.
Patients with known hypersensitivity or intolerance to the drug or any other component of the tablet.
Epilepsy. Metoclopramide should not be used in patients with epilepsy since it may increase the frequency and severity of seizures.
Concomitant use with other drugs likely to cause extrapyramidal side effects. The frequency and severity of extrapyramidal reactions may be increased with neuroleptics such as phenothiazines.
Patients with porphyria.
Metoclopramide should not be administered to patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of extrapyramidal reactions may be increased.
Metoclopramide should not be used in children below 1 year of age.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Persistent tardive dyskinesia.

Tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high dose therapy, especially females. The symptoms are persistent and can oftentimes appear to be irreversible. The syndrome is characterised by rhythmical involuntary movement of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities. There is no known effective treatment for tardive dyskinesia; however, in some patients symptoms may lessen or resolve after metoclopramide treatment is stopped. Antiparkinson agents usually do not alleviate the symptoms of this syndrome.
Although the risk of tardive dyskinesia with metoclopramide has not been extensively studied, one published study reported a tardive dyskinesia prevalence of 20% among patients treated for at least 3 months. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the total cumulative dose.
Metoclopramide therapy should routinely be discontinued in patients who develop signs or symptoms of tardive dyskinesia. It has been suggested that fine vermicular movements of the tongue may be an early sign of the syndrome, and, if the medication is stopped at that time, the syndrome may not develop. Tardive dyskinesia may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. Metoclopramide itself, however, may suppress (or partially suppress) the signs of tardive dyskinesia, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of the syndrome is unknown. Therefore, metoclopramide should not be used for the symptomatic control of tardive dyskinesia.
Prolonged treatment (greater than 12 weeks) with metoclopramide should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risks to the patient of developing tardive dyskinesia.
Care should be exercised in patients being treated with other centrally active drugs.
Since extrapyramidal symptoms may occur with both metoclopramide and neuroleptics such as phenothiazines, care should be exercised in the event of both drugs being prescribed concurrently (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). The frequency and severity of seizures or extrapyramidal reactions may be increased in epileptic patients given metoclopramide.

Dystonia.

Dystonic reactions occur in approximately 1% of patients given metoclopramide. These occur more frequently in children and young adults, and may occur after a single dose (see Section 4.8 Adverse Effects (Undesirable Effects)).

Neuroleptic malignant syndrome.

This has been reported with metoclopramide in combination with neuroleptics as well as with metoclopramide monotherapy (see Section 4.8 Adverse Effects (Undesirable Effects)).

Prolactin levels.

Since metoclopramide elevates prolactin levels and the elevation persists during chronic administration, it should be used with caution in patients with breast cancer. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhoea, amenorrhoea, gynaecomastia and impotence have been reported with prolactin elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of prolactin stimulating neuroleptic drugs. However, neither clinical nor epidemiological studies conducted to date have shown an association between chronic administration of these drugs and mammary tumourigenesis; the available evidence is too limited to be conclusive at this time.

Surgery.

After operations such as pyloroplasty or gut anastomosis, metoclopramide therapy should be withheld for three or four days as vigorous muscular contractions may impede healing.

Masking of serious illness.

The symptomatic relief provided by metoclopramide may delay recognition of serious disease. It should not be prescribed until diagnosis has been established, and should not be substituted for appropriate investigation of the patient's symptoms.

Depression.

Metoclopramide induced depression has been reported in patients without a prior history of depression. Symptoms have ranged from mild to severe and have included episodes of spontaneous, uncontrollable crying, somnolence, suicide ideation and suicide. Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks.

Hypertension.

In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines. Caution should be exercised when metoclopramide is used in patients with hypertension.

Parkinson's disease.

Metoclopramide can exacerbate Parkinsonian symptoms, thus it should be used with caution, if at all, in patients with Parkinsonian syndrome (see Section 4.8 Adverse Effects (Undesirable Effects)).

Vomiting.

If vomiting persists in a patient receiving metoclopramide, the patient should be reassessed to exclude the possibility of an underlying disorder; e.g. cerebral irritation.

Use in hepatic impairment.

In patients with clinically significant degrees of hepatic impairment, clearance of Pramin is likely to be reduced.

Use in renal impairment.

In patients with clinically significant degrees of renal impairment, clearance of Pramin is likely to be reduced.
Special care should be taken in cases of severe renal insufficiency (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

To avoid adverse reactions, adhere strictly to dosage recommendations. When prolonged therapy is considered necessary, patients should be regularly reviewed.

Paediatric use.

Metoclopramide is contraindicated in children less than 1 year of age. Metoclopramide should not be given to children less than 20 years of age unless a clear indication has been established for its use, because of the higher incidence of adverse reactions in this age group.

Effects on laboratory tests.

Metoclopramide may blunt the response to the gonadorelin diagnostic test, by increasing serum prolactin levels. Metoclopramide may alter hepatic function test results.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Due to its pharmacologic effects on transit time in the stomach and small intestine, metoclopramide may alter the absorption of certain drugs. The extent of absorption of drugs that disintegrate, dissolve and/or are absorbed mainly in the stomach (e.g. digoxin) may be diminished by metoclopramide, whereas the rate and extent of absorption of drugs that are mainly absorbed in the small intestine (e.g. paracetamol, aspirin, diazepam, ethanol, levodopa, lithium, tetracycline) may be enhanced. The clinical importance of these effects has not been established.

Anticholinergic drugs and opioid analgesics.

The effects of metoclopramide on gastrointestinal motility can be antagonised by anticholinergic drugs and opioid analgesics.

CNS depressants.

Metoclopramide may potentiate the action of other CNS depressants such as opiates or other analgesics, barbiturates or other sedatives, hypnotics, tranquillisers, anaesthetics or alcohol.

Ciclosporin.

The decrease in gastric emptying time caused by metoclopramide may increase the bioavailability of ciclosporin. Monitoring of ciclosporin concentrations may be necessary.

Neuroleptics.

Metoclopramide may cause extrapyramidal symptoms in some patients. Therefore, when metoclopramide is used concomitantly with other drugs that are likely to cause extrapyramidal reactions (e.g. neuroleptics such as phenothiazines), caution should be exercised (see Section 4.3 Contraindications).

Monoamine oxidase inhibitors (MAOI).

The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving MAOIs.

Compatibility.

If the standard formulation of Pramin is used for the treatment of nausea and vomiting associated with cytotoxic drugs, the cytotoxic agent should be administered as a separate infusion.
When metoclopramide is given concurrently with suxamethonium the recovery time is prolonged.
Since metoclopramide influences the delivery of food to the intestine and thus, the rate of its absorption, the administration of metoclopramide may result in poor diabetic control in some patients. Therefore adjustment in, or timing of, insulin dosage may be necessary in insulin controlled diabetics.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Category A: drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Although animal tests in several mammalian species have shown no teratogenic effects, the safety of metoclopramide in pregnancy has not been established. Adequate human data is not available. Therefore, the drug should only be used in pregnant women when the expected benefit outweighs any potential risk.
Metoclopramide is excreted in human milk. It is not known whether it has a harmful effect on the newborn. Administration of metoclopramide to breastfeeding mothers is not recommended unless the expected benefits to the mother outweigh any potential risk to the baby. The increased risk of adverse reactions in young children should be taken into account in making a risk/ benefit assessment.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about engaging in activities requiring mental alertness for a few hours after metoclopramide has been administered.

4.8 Adverse Effects (Undesirable Effects)

Neurological.

Adverse effects to metoclopramide that are most frequently seen are restlessness, drowsiness, fatigue and lassitude, which occur in approximately 10% of patients. Insomnia, headache, dizziness, have been reported less frequently. Acute depression has been reported rarely (less than 1 in 1000 cases). Anxiety or agitation may occur. Delirium, severe dysphoria, obsessive rumination and mania have been reported occasionally.
Parkinsonian symptoms, including tremor, rigidity, bradykinesia and akinesia, occur rarely in patients receiving metoclopramide but may be associated with usual or excessive doses or with decreased renal function.
Various extrapyramidal reactions to metoclopramide, usually of the dystonic type, have been reported. Acute dystonic reactions occur in approximately 0.2% of patients treated with 30 to 40 mg of metoclopramide per day. In cancer chemotherapy patients receiving 1 to 2 mg/kg per dose, the incidence is 2% in patients over the ages of 30 to 35 and 25% or higher in children and young adults who have not had prophylactic administration of diphenhydramine. Reactions include spasm of the facial muscles, trismus, rhythmic protrusion of the tongue, a bulbar type of speech, spasm of the extraocular muscles including oculogyric crisis, unnatural positioning of the head and shoulders and opisthotonos. There may be a generalised increase in muscle tone. The majority of reactions occur within 36 hours of starting treatment and the effects usually disappear within 24 hours of withdrawal of the drug. However, close observation is required and in cases of more severe reactions an antiparkinson drug such as benztropine, or an anticholinergic antihistamine such as diphenhydramine, should be given. A fatal acute dystonic reaction has been reported in a patient who received hexamethylmelamine, cisplatin and metoclopramide high dose.
Dystonic reactions may present rarely as upper airway obstruction with stridor and dyspnoea, possibly secondary to laryngospasm or supraglottic dystonia. A fatal cardiorespiratory arrest occurred in at least one patient with an acute dystonic reaction.
Tardive dyskinesia, which may be persistent, has been reported particularly in elderly patients (particularly women) following long-term therapy with metoclopramide. Tardive dyskinesia is most frequently characterised by involuntary movements of the tongue, face, mouth or jaw and sometimes by involuntary movements of the trunk and/or extremities. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase with increasing duration of therapy and total cumulative dose. Although tardive dyskinesia can occur after relatively brief therapy with the drug at low doses, it appears to be more readily reversible under such circumstances (see Section 4.4 Special Warnings and Precautions for Use).

Neuroleptic malignant syndrome (NMS).

NMS has been reported very rarely (less than 1 in 10,000). NMS is potentially fatal and comprises hyperpyrexia, altered consciousness, muscle rigidity, autonomic instability and elevated levels of CPK, and must be treated urgently (recognised treatments include dantrolene and bromocriptine). Metoclopramide should be stopped immediately if NMS occurs.

Gastrointestinal.

Nausea or bowel disturbances have been reported.

Hepatic.

Rarely, cases of hepatotoxicity, characterised by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential.

Renal.

Urinary frequency and incontinence.

Cardiovascular.

Atrial fibrillation, oedema, ventricular fibrillation, ventricular tachycardia, palpitations and tachycardia have been associated with the use of metoclopramide.

Endocrine.

Raised serum prolactin levels have been observed during metoclopramide therapy; this effect is similar to that noted with many other compounds. Galactorrhoea and breast enlargement have also been observed during metoclopramide therapy.

Hypersensitivity.

There have been isolated reports of hypersensitivity reactions in patients receiving metoclopramide.

Respiratory.

Respiratory failure, secondary to dystonic reaction, acute asthmatic symptoms of wheezing and dyspnoea may occur.

Other effects.

There have been isolated reports of blood disorders. Methaemoglobinaemia, particularly following overdose in neonates, has also occurred in patients receiving the drug. A few cases of neutropenia, leucopenia or agranulocytosis, generally without clear-cut relationship to metoclopramide.
There have been isolated reports of hypersensitivity reactions (such as urticaria, maculopapular rash) in patients receiving metoclopramide.
Sexual dysfunction, priapism and muscle spasm may also occur.
Hyperthermia has also been observed.
Sulfhaemoglobinaemia in adults.

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

Clinical features.

Overdose of metoclopramide may be expected to produce effects that are extensions of common adverse reactions: drowsiness, disorientation and extrapyramidal reactions have been the principal effects reported. Other reported effects associated with metoclopramide overdose have included feelings of anxiety or restlessness, headache, vertigo, nausea, vomiting, constipation, weakness, hypotension and xerostomia. A-V block has been observed very rarely.

Management.

Treatment of metoclopramide overdosage generally involves symptomatic and supportive care. Extrapyramidal reactions may be controlled by antiparkinsonian agents such as benztropine, or antihistamines with anticholinergic action such as diphenhydramine. Appropriate therapy should be instituted if hypotension or excessive sedation occurs. Methaemoglobinaemia should be treated with methylene blue. Haemodialysis and continuous ambulatory peritoneal dialysis appears ineffective in removing metoclopramide.
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.

Metoclopramide increases the motility of the stomach, pylorus and small intestine without stimulating gastric, biliary or pancreatic secretions. Its mode of action is unclear, however it appears to sensitise tissues to the action of acetylcholine. The gastrointestinal stimulant action is exerted peripherally, not by central stimulation of the vagus nerve, and it is blocked by anticholinergic drugs such as atropine.
The antiemetic properties of metoclopramide result from its antagonism of central dopamine receptors and from its effect on the stomach. It increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower oesophageal sphincter and has little, if any, effect on the motility of the colon or gall bladder.
Metoclopramide causes increased prolactin secretion due to blocking of dopamine receptors in the hypothalamus and hypophysis which normally suppress prolactin secretion. Metoclopramide also increases the rate of secretion of aldosterone. In vitro studies suggest that metoclopramide acts directly on adrenal tissue to stimulate aldosterone secretion.
Metoclopramide has dopamine antagonist activity. Like the phenothiazines and related drugs, which are also dopamine antagonists, it produces sedation and may produce extrapyramidal reactions (see Section 4.4 Special Warnings and Precautions for Use). Metoclopramide inhibits the central and peripheral effects of apomorphine, induces release of prolactin and causes a transient increase in circulating aldosterone levels.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The onset of pharmacological action of metoclopramide is 30 to 60 minutes following an oral dose and effects persist for one to two hours.
After oral administration of metoclopramide there is marked variability in peak plasma concentrations observed. The variation in peak plasma levels between individuals is thought to be due to first-pass metabolism.

Distribution.

Plasma protein binding of metoclopramide appears to be minor (13 to 22%).

Metabolism.

About 80% of the drug is excreted in urine in the first 24 hours. Approximately half the amount excreted is a glucuronide or sulphate conjugate with the remainder unchanged.

Excretion.

Elimination half-life varies in different studies from 2.5 to 5 hours. In one study 78% of the drug was excreted in the urine during the first 24 hours after a 10 mg oral dose.
Impaired renal function results in reduced clearance of metoclopramide and an increased elimination half-life (15 hours). In a study of 6 patients with chronic renal failure total body clearance of metoclopramide was 16.7 litres/hour compared to 52.5 litres/hour in normal individuals. This difference in clearance was not explained by the change in renal clearance and suggested impaired metabolism or an alteration in enterohepatic circulation.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following excipients: lactose anhydrous, pregelatinised maize starch, microcrystalline cellulose, colloidal anhydrous silica and magnesium stearate.

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

Store below 30°C.

6.5 Nature and Contents of Container

Container type.

HDPE bottle with PP child-resistant closure or PVC/PVdC-Al blister pack.

*Pack sizes.

Available in bottles of 6, 25, 30, 50, 90, 100 and 1000 tablets or a blister pack of 25 tablets.
* Not all pack sizes are marketed in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Chemical name: 4-amino- 5-chloro-N-(2-diethylaminoethyl)- 2-methoxybenzamide hydrochloride monohydrate.
Structural formula:
Molecular formula: C14H22ClN3O2,HCl,H2O. Molecular weight: 354.3.
Metoclopramide hydrochloride is a white or almost white, crystalline powder; odourless or almost odourless. It is soluble in 0.7 parts of water, in 3 parts of ethanol (96%) and in 55 parts of chloroform. It is practically insoluble in ether.

CAS number.

54143-57-6.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes