Consumer medicine information

Pramin

Metoclopramide hydrochloride

BRAND INFORMATION

Brand name

Pramin

Active ingredient

Metoclopramide hydrochloride

Schedule

SUMMARY CMI

PRAMIN

Consumer Medicine Information (CMI) summary

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

1. Why am I taking PRAMIN?

PRAMIN contains the active ingredient metoclopramide hydrochloride. PRAMIN is used to manage nausea and vomiting.

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

2. What should I know before I take PRAMIN?

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

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

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

3. What if I am taking other medicines?

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

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

4. How do I take PRAMIN?

Adults 20 years and over - 1 tablet every 8 hours.
Adolescents: 15 to 19 years - ½ to 1 tablet every 8 hours.
The dose varies with the age of the patient and reason for use. Children and adolescents are very sensitive to the effects of PRAMIN. Your doctor will normally start the treatment at the lower dose.

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

5. What should I know while taking PRAMIN?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are taking PRAMIN. Tell your doctor if nausea and vomiting persist. Tell your doctor if you become pregnant while taking PRAMIN. If you are going to have surgery, tell the surgeon or anaesthetist you are taking PRAMIN.
Things you should not do	Do not exceed the recommended dose. Do not give this medicine to anyone else, even if they have the same condition as you.
Driving or using machines	Be careful before you drive or use any machines or tools until you know how PRAMIN affects you. PRAMIN may cause dizziness, light-headedness, tiredness or drowsiness in some people.
Drinking alcohol	Drinking alcohol whilst taking PRAMIN may make you sleepy.
Looking after your medicine	Store in a cool dry place where the temperature stays below 30°C. Keep your tablets in the original container until it is time to take them.

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

6. Are there any side effects?

Less serious side effects include drowsiness, tiredness, restlessness, dizziness, headache, bowel irregularities, insomnia, anxiety and agitation.

Some of the more serious side effects include uncontrolled or repeated movements, (e.g., sucking or smacking of the lips, darting of the tongue, chewing movements, uncontrolled movements of the arms or legs), fast or irregular heartbeat, depression, and swelling of hands, ankles or feet.

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

FULL CMI

PRAMIN

Active ingredient(s): metoclopramide hydrochloride

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking PRAMIN?

PRAMIN contains the active ingredient metoclopramide hydrochloride. 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 upper intestine.

PRAMIN is used in adults 20 years and over to:

treat nausea and vomiting caused by infectious diseases, migraine, kidney disease, childbirth, other medications, cancer, or following surgery, chemotherapy or radiation treatment.
activate stomach contractions in conditions where there is a need to encourage normal passage of food through the stomach and intestines. E.g., certain stomach problems associated with diabetes.
with X-rays to help diagnose problems of the stomach and/or intestines.
help with passing tubes into the intestine.

PRAMIN is used in young adults 15 - 19 years of age to:

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

2. What should I know before I take PRAMIN?

Warnings

Do not take PRAMIN if you:

are allergic to 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
rash, itching or hives on the skin
Always check the ingredients to make sure you can take this medicine.
have active bleeding from the stomach and/or digestive tract.
have a blockage of the stomach and/or digestive tract.
have had recent surgery of the stomach and/or digestive tract.
have phaeochromocytoma (an adrenaline producing tumour of the adrenal gland).
have epilepsy (fits or seizures).
take other medication likely to cause extrapyramidal effects, such as antipsychotic/neuroleptic medication 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.

Check with your doctor if you:

have any other medical conditions including:
- Parkinson's disease - a condition affecting muscle control and movement
- liver or kidney problems
- high blood pressure
- asthma
- depression
- breast cancer
take any medicines for any other condition
have allergies to any other medicines, foods, dyes or preservatives.

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.

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

Pregnancy and breastfeeding

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

Your doctor will discuss the risks and benefits of taking this medicine during pregnancy.

Talk to your doctor if you are breastfeeding or intend 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.

3. What if I am taking other medicines?

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

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

medicines used to help you sleep (tranquilisers) and/or to relieve anxiety
pain relievers (e.g., paracetamol, codeine or morphine)
sedatives or sleeping medication
atropine-like medications (e.g., some cold preparations, travel sickness medicines, stomach cramp medicines)
tetracycline antibiotics,
levodopa, a medicine used in the treatment of Parkinson's disease
digoxin, a medicine used to treat heart failure
ciclosporin, a medicine used to help prevent organ transplant rejection
monoamine oxidase inhibitors, a group of medicines used to treat depression
certain medicines used to treat mental disorders, including lithium, thioridazine

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

4. How do I take PRAMIN?

How much to take

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

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

Do not exceed the prescribed dose.

Adults 20 years and over - 1 tablet every 8 hours.
Adolescents: 15 to 19 years - ½ to 1 tablet every 8 hours.
The daily dosage of PRAMIN, especially for children and adolescents, should not normally exceed 0.5mg/kg bodyweight or 30 mg daily.
Children and adolescents 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.

If you are taking PRAMIN before a diagnostic procedure your doctor will give you your dose.

This will usually be a single dose of 1-2 tablets depending on your age.

If you have significant kidney or liver impairment your doctor may prescribe a lower dose.

When to take PRAMIN

PRAMIN is best taken 30 minutes before symptoms are likely to occur or 30 minutes before meals. Space the doses of PRAMIN evenly throughout your day.
Your doctor may tell you to take PRAMIN only when required for each occasion of nausea and vomiting.

How to take PRAMIN

Swallow the tablets with a full glass of water.
The tablets can be broken in half (along the break-line).

How long to take PRAMIN

Your doctor will advise you how long to take PRAMIN. The maximum recommended treatment duration is 5 days.

If you forget to take PRAMIN

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 tablet 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 take too much PRAMIN

If you think that you or anyone else has taken too much PRAMIN, urgent medical attention may be needed.

Symptoms of an overdose may include drowsiness, confusion, dizziness, headache, agitation, nausea, vomiting, constipation, tremor, twitching or uncontrolled spasm or muscles.

You should immediately:

phone the Poisons Information Centre
(Australia telephone 13 11 26) for advice, or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

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

5. What should I know while taking PRAMIN?

Things you should do

Call your doctor if:

nausea and vomiting persist.
you become pregnant while taking PRAMIN.

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

It may affect other medicines used during the surgery.

If you have any liver function tests or other tests, tell your doctor.

PRAMIN may affect the results of some tests.

Remind any doctor, dentist or pharmacist you visit that you are taking PRAMIN.

Things you should not do

Do not use PRAMIN to treat any other conditions unless your doctor tells you to.
Do not give your medicine to anyone else, even if they have the same condition as you.

Driving or using machines

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

PRAMIN may cause dizziness, light-headedness, tiredness, or drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery, or do anything else that could be dangerous. Children should be careful when riding bicycles or climbing trees.

Drinking alcohol

Tell your doctor if you drink alcohol.

Combining PRAMIN and alcohol can make you sleepy.

Looking after your medicine

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

PRAMIN should be stored in a cool dry place below 30°C away from moisture, heat or sunlight; for example, do not store it:

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

Heat or dampness can destroy some medicines.

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.

Getting rid of any unwanted medicine

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

Do not take this medicine after the expiry date or if the packaging is torn or shows signs of tampering.

6. Are there any side effects?

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

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

Less serious side effects

Less serious side effects	What to do
drowsiness, tiredness, fatigue restlessness dizziness, headache bowel irregularities, diarrhoea, constipation insomnia (trouble sleeping) anxiety agitation restlessness breast enlargement, unusual secretion of breast milk	Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects	What to do
uncontrolled or repeated movements, e.g., sucking or smacking of the lips, darting of the tongue, chewing movements, uncontrolled movements of the arms or legs. This may be a sign of tardive dyskinesia, a movement disorder which can potentially be irreversible fast or irregular heartbeat depression yellowing of the skin or eyes swelling of hands, ankles or feet	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Very serious side effects

Serious side effects

What to do

allergic reaction including fainting, swelling of limbs, face, lips, mouth or throat which may cause difficulty swallowing or breathing, wheezing or shortness of breath
sudden uncontrolled muscle spasm, stiffness of the arms or legs, muscle spasm of the face, locked-jaw or upturned eyes
shuffling walk, slowing of all movement, muscle tremor
neuroleptic malignant syndrome, a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions

Stop taking PRAMIN and call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PRAMIN even if you do not think that it is connected with the medicine.

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

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

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

Reporting side effects

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

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

7. Product details

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

There is no evidence that PRAMIN is addictive.

What PRAMIN contains

Active ingredient (main ingredient)	metoclopramide hydrochloride 10mg (as hydrate)
Other ingredients (inactive ingredients)	lactose anhydrous pregelatinised maize starch microcrystalline cellulose colloidal anhydrous silica magnesium stearate
Potential allergens	lactose trace amounts of sulfites

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

What PRAMIN looks like

PRAMIN is a white, normal convex tablet marked "ME" over "10" on one side and "G" on the reverse (AUST Rs 364450 & 17661).

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

Who distributes PRAMIN

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

This leaflet was prepared in January 2025.

PRAMIN_cmi\Jan25/00

Published by MIMS March 2025

BRAND INFORMATION

Brand name

Pramin

Active ingredient

Metoclopramide hydrochloride

Schedule

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 aged 15 - 19 years.

The use of Pramin in young adults 15 - 19 years should be restricted to the following situations and only 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

Metoclopramide injection is not available in the Pramin brand. However, injection formulations are available in other brands. Where information obtained from metoclopramide injection formulations is included in this PI, this is intended for prescriber information.
Where correct dosing requires a metoclopramide injection formulation, the specific product information for these formulations should be referred to for complete dosage and administration instructions.
Tablets should not be used in children less than 15 years.

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 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 15-19 years.

5 to 10 mg three times daily, commencing at the lower dosage and used as a second line therapy only.

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.

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 tablets should not be used in children below 15 years 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 tablets are contraindicated in children less than 15 years of age 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.
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).

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Pramin

Metoclopramide hydrochloride

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Pramin 10 mg Tablets