Consumer medicine information

Metoclopramide Injection

Metoclopramide hydrochloride

BRAND INFORMATION

Brand name

Bridgewest Metoclopramide Injection BP

Active ingredient

Metoclopramide hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metoclopramide Injection.

SUMMARY CMI

Metoclopramide Injection

Consumer Medicine Information (CMI) summary

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

1. Why am I given Metoclopramide Injection?

Metoclopramide Injection contains the active ingredient metoclopramide hydrochloride monohydrate.

Metoclopramide Injection is used to relieve nausea and vomiting in migraine, cancer treatment, childbirth and infectious diseases; control vomiting after surgery; or to help with placing tubes into the intestine in adults over 20 years of age.

Metoclopramide Injection is used as second line therapy to treat severe vomiting of known cause or following chemotherapy or radiation treatment; or to help with placing tubes into the intestine in young adults and children (over 1 year of age).

For more information, see Section 1. Why am I given Metoclopramide Injection? in the full CMI.

2. What should I know before receiving Metoclopramide Injection?

Do not use if you have ever had an allergic reaction to metoclopramide, or any other similar medicines, such as procaine, procainamide.

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 receiving Metoclopramide Injection? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Metoclopramide Injection 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 is Metoclopramide Injection given?

Metoclopramide Injection will be given to you by a doctor or nurse as an injection into the muscle or by slow injection into a vein.

More information can be found in Section 4. How is Metoclopramide Injection given? in the full CMI.

5. What should I know while receiving Metoclopramide Injection?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are receiving Metoclopramide Injection.
  • Tell your doctor you are receiving this medicine if you are going to have surgery, an operation or dental treatment. It may affect other medicines used during surgery.
  • Tell your doctor if you are about to have any blood tests that you are taking this medicine. It may interfere with the results of some tests.
  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Metoclopramide Injection affects you. Metoclopramide Injection may cause dizziness, light-headedness, tiredness or drowsiness in some people. Children should be careful when riding bicycles or climbing trees.
Drinking alcohol
  • Do not drink alcohol while you are receiving Metoclopramide Injection.

For more information, see Section 5. What should I know while receiving Metoclopramide Injection? in the full CMI.

6. Are there any side effects?

Common and/or serious side effects are drowsiness, tiredness, restlessness, dizziness, headache, nausea, bowel irregularities, insomnia, fast heartbeat, depression, suicidal thoughts.

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

Metoclopramide Injection

Active ingredient(s): Metoclopramide hydrochloride monohydrate

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

1. Why am I given Metoclopramide Injection?
2. What should I know before receiving Metoclopramide Injection?
3. What if I am taking other medicines?
4. How is Metoclopramide Injection given?
5. What should I know while receiving Metoclopramide Injection?
6. Are there any side effects?
7. Product details

1. Why am I given Metoclopramide Injection?

Metoclopramide Injection contains the active ingredient metoclopramide hydrochloride monohydrate. Metoclopramide Injection belongs to a group of medicines known as antiemetics. Antiemetics stop or prevent nausea and vomiting. It also acts in the stomach and upper intestine to increase muscle contractions.

Metoclopramide Injection is used in adults over 20 years of age to:

  • relieve nausea and vomiting in migraine, cancer treatment, childbirth and infectious diseases
  • control vomiting after surgery
  • help with placing tubes into the intestine.

When used to treat young adults and children (over 1 year of age), Metoclopramide Injection is only used as second line therapy to:

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

2. What should I know before receiving Metoclopramide Injection?

Warnings

Do not use Metoclopramide Injection if:

  • you are allergic to metoclopramide, or any other similar medicines, such as procaine, procainamide.
    Always check the ingredients to make sure you can use this medicine.
  • you have or have had any medical conditions, especially the following:
    - phaeochromocytoma (a rare tumour of the adrenal gland that may cause high blood pressure)
    - bleeding of the stomach and/or digestive tract
    - blockage of the stomach and/or digestive tract
    - take other medication such as antipsychotic/ neuroleptic medication and certain antidepressants that can cause movement disorders (extrapyramidal reactions)
    - porphyria (rare disease of blood pigments)
    - epilepsy (fits or seizures).

If you are not sure whether any of these apply to you, check with your doctor.

Check with your doctor if you:

  • have or have had any medical conditions, especially the following:
    - tardive dyskinesia, a disorder of constant, uncontrollable movements of the tongue, mouth, jaw and cheeks
    - neuroleptic malignant syndrome. Symptoms may include fever, severe muscle cramps/stiffness, sweating, tremors, incontinence, palpitations, unstable blood pressure
    - breast cancer
    - epilepsy (fits or seizures)
    - recent stomach surgery in the past 4 days
    - depression, including suicidal thoughts
    - high blood pressure
    - kidney problems
    - liver problems
    - parkinson's disease.

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

Tell your doctor if you are pregnant or plan to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Metoclopramide is excreted in breast milk, and can be absorbed by your baby if you are breastfeeding.

Children below 1 year of age

Metoclopramide Injection should not be used in children below 1 year of age.

3. What if I am taking other medicines?

Tell your doctor 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 Metoclopramide Injection may interfere with each other. These include:

  • painkillers
  • sleeping tablets
  • certain drugs used to treat psychiatric disorders including depression
  • suxamethonium
  • penicillin antibiotics
  • medicines used to treat Parkinson's disease, such as bromocriptine, dopamine or levodopa
  • medicines used to treat stomach disorders, such as cimetidine or hyoscine
  • medicines used for cancer treatments
  • quinidine, used to treat malaria infections, and also heart rhythm disorders
  • digoxin, used to treat heart disorders
  • cyclosporin, used to alter the immune system in patients who receive an organ transplant
  • insulin, used to treat diabetes.

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

4. How is Metoclopramide Injection given?

How much is given

Your doctor will decide what dose and how long you will receive Metoclopramide Injection. The dosage you will be given will depend on your condition, what it is being used for and other factors, such as your age, and whether or not other medicines are being given at the same time.

How is it given

Metoclopramide Injection will be given to you by a doctor or nurse as an injection into the muscle or by slow injection into a vein.

If you are given too much

This rarely happens as Metoclopramide Injection will be given to you under the care of a highly trained doctor.

In the unlikely event that you are given too much (an overdose), you may experience some of the effects listed under Section 6. Are there any side effects?

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

5. What should I know while receiving Metoclopramide Injection?

Things you should do

  • If you are about to be started on any new medicine, remind your doctor or pharmacist that you are having Metoclopramide Injection.
  • Tell any other doctors, dentists, and pharmacists who treat you that you are having this medicine.
  • Tell your doctor, nurse or dentist you are taking this medicine if you are going to have surgery, an operation or dental treatment. It may affect other medicines used during surgery.
  • Tell your doctor if you are about to have any blood tests that you are having this medicine. It may interfere with the results of some tests.
  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Driving or using machines

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

Metoclopramide Injection 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

Do not drink alcohol while you are being given Metoclopramide Injection.

Looking after your medicine

Metoclopramide Injection is usually stored in the hospital ward, clinic or at the pharmacy.

Your doctor, nurse or pharmacist is responsible for storing Metoclopramide Injection in a cool dry place, protected from light where the temperature stays below 25°C and disposing of any unused product correctly.

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 effectsWhat to do
  • drowsiness, tiredness
  • restlessness
  • dizziness
  • headache
  • nausea
  • bowel irregularities
  • insomnia
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • fast heartbeat
  • depression, suicidal thoughts
Tell your doctor as soon as possible if you notice any of these serious side effects.
You may require medical attention.
  • allergic reaction including fainting, swelling of limbs, face, lips, mouth or throat which may cause difficulty swallowing or breathing
  • 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 be potentially irreversible
  • shuffling walk, slowing of all movement, muscle tremor
  • a sudden increase in body temperature, extremely high blood pressure and severe convulsions (neuroleptic malignant syndrome)
  • jaundice or a yellowing of the skin or eyeballs, often with fever, fatigue, loss of appetite, dark coloured urine or light coloured bowel movements.
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.

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

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

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, nurse 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.

What Metoclopramide Injection contains

Active ingredient
(main ingredient)		Metoclopramide hydrochloride monohydrate
Other ingredients
(inactive ingredients)		Hydrochloric acid
Sodium chloride
Sodium hydroxide
Water for Injections

Tell your doctor or nurse if you are allergic to any of these ingredients.

What Metoclopramide Injection looks like

Metoclopramide Injection is a clear, colourless solution in a plastic ampoule.

Metoclopramide Injection 10 mg in 2 mL is available in packs of 10 or 50 ampoules (AUST R 11364)

* Not all pack sizes may be marketed.

Who manufactures and distributes Metoclopramide Injection

Bridgewest Perth Pharma Pty Ltd
15 Brodie Hall Drive
Bentley WA 6102
Telephone: 1800 161 156
[email protected]

This leaflet was prepared in September 2023.

Published by MIMS November 2023

BRAND INFORMATION

Brand name

Bridgewest Metoclopramide Injection BP

Active ingredient

Metoclopramide hydrochloride

Schedule

S4

 

1 Name of Medicine

Metoclopramide hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Metoclopramide Injection BP contains metoclopramide hydrochloride 10 mg in 2 mL (as monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Metoclopramide Injection BP is a clear, colourless, sterile, preservative-free solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults (20 years and over).

Relief of nausea and vomiting associated with migraine, cancer therapy (chemotherapy or radiation), malignant disease, labour, infectious disease and uraemia;
control of post-operative vomiting;
assist in small bowel intubation.
Metoclopramide is of little benefit for the prevention or treatment of motion sickness.

Young adults and children (over 1 year of age).

Metoclopramide should be restricted to the following conditions and only used as second line therapy, when used to treat children and young adults under 20 years of age because of the risk of adverse effects:
severe intractable vomiting of known cause;
vomiting associated with radiation therapy or intolerance to cytotoxic drugs;
assist in small bowel intubation.

4.2 Dose and Method of Administration

Dosage.

The dosage recommendations should be strictly adhered to in order to minimise the possibility of dystonic side effects. Metoclopramide should only be used after careful examination has excluded any underlying disorder (such as cerebral irritation) that may have induced nausea and vomiting.
Total daily doses of metoclopramide should not normally exceed 0.5 mg/kg bodyweight with a maximum of 30 mg daily. This should be less (if possible) in children and young adults, when given by injection. Maximum recommended treatment duration is 5 days in all age groups.
Usual dosage is as follows and should be administered intramuscularly or by slow intravenous injection over 1 to 2 minutes.
Adults.

20 years and over.

Maximum of 10 mg three times a day.
Young adults. Treatment of young adults should commence at the lower dosage, and used as second line therapy only.

15-19 years.

5 mg to 10 mg three times a day.
Children. Treatment of children should commence at the lower dosage, where stated, and used as second line therapy only.

5-14 years.

2.5 mg to 5 mg three times a day.

3-5 years.

2 mg two to three times a day.

1-3 years.

1 mg two to three times a day.

Diagnostic indications.

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

20 years and over.

10 mg to 20 mg.
Young adults.

15-19 years.

10 mg.
Children.

9-14 years.

5 mg.

5-9 years.

2.5 mg.

3-5 years.

2 mg.

1-3 years.

1 mg.

Dosage adjustment.

Use in special patient populations.

Elderly patients.

To avoid adverse reactions strict adherence to dosage recommendations is advised and, where prolonged therapy is considered necessary, patients should be regularly reviewed.

Patients with renal impairment.

Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the usual dose. Subsequent dosage will depend on individual clinical response.

Patients with hepatic impairment.

Metoclopramide undergoes hepatic metabolism via simple conjugation. Its safe use has been described in patients with advanced liver disease whose renal function was normal. It is suggested that therapy be initiated as half the recommended dose with subsequent dose adjustment being made as the individual response has been determined.

Method of administration.

Compatibility.

Intravenous fluids.

No preservative is included in the formulation of Metoclopramide Injection BP. Therefore, to reduce microbiological hazard, admixture to intravenous fluids should be performed under aseptic conditions and the infusion commenced as soon as possible after preparation and in any case within 24 hours of preparation. If storage is necessary, keep at 2°C to 8°C.
The literature indicates that Metoclopramide Injection BP may be added to the following solutions:
glucose 5% in sodium chloride 0.45%;
glucose 5% in water;
mannitol 20%;
sodium chloride 0.9%;
Ringer's injection;
Ringer's injection, lactated (Hartmann's solution).

Narcotic analgesics.

Morphine sulfate: 1 mg/mL with metoclopramide hydrochloride 0.2 mg/mL in glucose 5% in water visually compatible for a 4 hour study period at 25°C under fluorescent light.
Pethidine hydrochloride: 10 mg/mL with metoclopramide hydrochloride 0.2 mg/mL in glucose 5% in water visually compatible for a 4 hour study period at 25°C under fluorescent light.

Cytotoxic drugs.

If the standard formulation of metoclopramide is used for the treatment of nausea and vomiting associated with cytotoxic drugs, the cytotoxic agent should be administered as a separate infusion.

4.3 Contraindications

Patients in whom increased gastrointestinal motility might be dangerous, e.g. presence of gastrointestinal haemorrhage, mechanical obstruction or perforation.
Phaeochromocytoma due to the possibility of a hypertensive crisis, probably due to release of catecholamines from the tumour.
Known hypersensitivity or intolerance to metoclopramide.

Note.

Patients sensitive to procaine and procainamide may be sensitive to metoclopramide.
Patients with porphyria.
Metoclopramide should not be used in patients with epilepsy since it may increase the frequency and severity of seizures.
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

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 often at times 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 movement 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 the 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.

Dystonic reactions.

Dystonic reactions occur in approximately 1% of patients given metoclopramide. These occur more often in children and young adults and may occur after a single dose.

Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome has been reported when metoclopramide has been used alone or in combination with neuroleptics (see Section 4.8 Adverse Effects (Undesirable Effects)).

Prolactin levels.

Metoclopramide elevates prolactin levels. and the elevation persists during chronic administration (see Section 4.8 Adverse Effects (Undesirable Effects)). This may be of importance in patients with previously detected breast cancer, in which the breast cancer is prolactin dependent. 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 prolactin elevating drugs have been associated with disturbances such as galactorrhoea, amenorrhoea, gynaecomastia and impotence, the clinical significance of elevated serum prolactin levels is not known for most patients. Chronic administration of prolactin stimulating neuroleptic drugs to rodents has shown an increase in mammary neoplasms. However, neither clinical nor epidemiological studies have shown an association between chronic administration of these drugs and mammary tumorogenesis in humans and the available evidence is too limited to be conclusive at this time.

Other.

Metoclopramide should be withheld for three to four days following operations such as pyloroplasty or gut surgery as vigorous muscular contractions may inhibit healing.
The effects of metoclopramide may mask symptoms and delay the recognition of a 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.
If vomiting persists in a patient being treated with metoclopramide, the patient's condition should be re-assessed to exclude the possibility of a more serious underlying disorder such as cerebral irritation.
Metoclopramide Injection BP should be administered slowly over 1-2 minutes by intravenous injection to avoid a transient but intense feeling of anxiety and restlessness, followed by drowsiness, which may occur with rapid administration.
Patients should be cautioned about engaging in activities requiring mental alertness for a few hours after the drug has been administered.
Metoclopramide induced depression has been reported in patients without a prior history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide (see Section 4.8 Adverse Effects (Undesirable Effects)). Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks.
Metoclopramide should be used with caution in patients with hypertension as intravenously administered metoclopramide has been shown to release catecholamines.
Patients receiving prolonged treatment with metoclopramide should be reviewed regularly.
Metoclopramide can exacerbate parkinsonian symptoms; therefore it should be used with caution, if at all, in patients with parkinsonian syndrome (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in hepatic impairment.

In patients with clinically significant degrees of hepatic impairment, clearance of metoclopramide is likely to be reduced (see Section 4.2 Dose and Method of Administration, Dosage adjustment).

Use in renal impairment.

In patients with clinically significant degrees of renal impairment, clearance of metoclopramide 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 and where 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 unless a clear indication has been established for its use. Children are at a greater risk of experiencing adverse reactions to metoclopramide.

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

Anticholinergic drugs and narcotic analgesics may antagonise the effects of metoclopramide on gastrointestinal motility.
Alcohol, sedatives, hypnotics, narcotics and tranquillisers have additive sedative effects when administered in conjunction with metoclopramide.
Due to its effects on gastric motility, metoclopramide may affect the rate of absorption of drugs from the gastrointestinal tract. Absorption of drugs such as paracetamol, aspirin in patients with migraine, cyclosporin, diazepam, dopamine, levodopa and morphine controlled release tablets, which are mainly absorbed from the small bowel, may be accelerated. Absorption of drugs such as digoxin, bromocriptine, cimetidine, penicillin and quinidine, which are mainly absorbed from the stomach, may be decreased.
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.
The decrease in gastric emptying time caused by metoclopramide may increase the bioavailability of cyclosporin. Monitoring of cyclosporin concentrations may be necessary.
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.
The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.
For compatibility with other medications, see Section 4.2 Dose and Method of Administration, Dosage adjustment; Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
As there are no adequate or well controlled studies in pregnant women, metoclopramide should be used only if clearly needed. Animal tests in several mammalian species and clinical experience have not indicated any teratogenic effect. However, metoclopramide is not recommended during the first three months of pregnancy unless there are compelling reasons to do so.
 As metoclopramide is excreted in human breast milk, its use is not recommended in nursing mothers unless the expected benefit outweighs the potential risk. The increased risk of adverse reactions in children should be considered when making a risk-benefit assessment.

4.7 Effects on Ability to Drive and Use Machines

Patients should be cautioned about engaging in activities requiring mental alertness for a few hours after the drug has been administered.

4.8 Adverse Effects (Undesirable Effects)

Neurological.

The most frequent adverse reactions to metoclopramide are restlessness, drowsiness, fatigue and lassitude, which occur in approximately 10% of patients.
Less frequently, insomnia, headache, dizziness may occur. Rare (less than 1 in 1,000 cases) of acute depression have been reported. Symptoms of metoclopramide induced depression have ranged from mild to severe and have included suicidal ideation and suicide (see Section 4.4 Special Warnings and Precautions for Use). Anxiety or agitation may occur, especially after rapid injection. Delirium, severe dysphoria, obsessive rumination and mania have been reported occasionally.
Although uncommon at normal dosage, 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 mg to 40 mg of metoclopramide per day. In cancer chemotherapy patients receiving 1 mg/kg 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 dystonic reaction has been reported in a patient who received hexamethylmelamine, cisplatin and high dose metoclopramide. 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) undergoing 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).
Very rare (less than 1 in 10,000) occurrences of neuroleptic malignant syndrome (NMS) have been reported. 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.
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.

Gastrointestinal.

Less frequently, nausea or bowel disturbances, may occur.

Cardiovascular.

A single case of supraventricular tachycardia following intramuscular administration has been reported. There have been very rare (less than 1 in 10,000) cases of abnormalities of cardiac conduction (such as bradycardia and heart block) in association with intravenous metoclopramide. Hypertension, hypotension, cardiac arrest, atrial fibrillation (AF), oedema, ventricular fibrillation, tachycardia, ventricular tachycardia and palpitations have also been associated with the use of metoclopramide. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised when metoclopramide is used in patients with hypertension.

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 (such as urticaria, maculopapular rash) in patients receiving metoclopramide.

Respiratory.

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

Genitourinary.

Urinary incontinence, sexual dysfunction, priapism and muscle spasm may also occur.

Hepatic disorders.

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.

Blood disorders.

There have been isolated reports of blood disorders. Methaemoglobinaemia, particularly following overdose in neonates, has also occurred in patients receiving the drug. Neutropenia, leucopenia and agranulocytosis has been reported.
Sulfhaemoglobinaemia in adults has been reported.

General disorders.

Hyperthermia has also been observed.

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

Signs and symptoms.

Limited information is available on the acute toxicity of metoclopramide. Overdosage 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 overdosage have included feelings of anxiety or restlessness, headache, vertigo, nausea, vomiting, constipation, weakness, hypotension and xerostomia; in addition generalised seizures and methaemoglobinaemia have occurred in infants. AV block has been observed very rarely.

Treatment of overdosage.

Treatment of metoclopramide overdose generally involves symptomatic and supportive care. There is no specific antidote for metoclopramide intoxication; however, agents with central anticholinergic activity (e.g. diphenhydramine, benztropine) may be useful in controlling extrapyramidal reactions. Symptoms of metoclopramide overdose are generally self limiting and usually subside within 24 hours. Appropriate therapy should be instituted if hypotension or excessive sedation occurs. Methaemoglobinaemia should be treated with methylene blue. Haemodialysis or peritoneal dialysis is unlikely to enhance the elimination of 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

Class of drug.

Antiemetic.

Mechanism of action.

Metoclopramide has antiemetic, antinauseant and gastrokinetic activity. It stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary or pancreatic secretions. The rate of gastric emptying is increased due to increased peristalsis of the jejunum and duodenum. The tone and amplitude of gastric contractions are increased, with relaxation of the pyloric sphincter and duodenal bulb. These effects combine to result in decreased intestinal transit time. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs. Metoclopramide has little, if any, effect on the motility of the colon or bladder. Metoclopramide also exhibits dopamine antagonist activity and consequently produces sedation and, rarely, other extrapyramidal reactions. It may have serotonin receptor (5HT3) antagonist properties. Metoclopramide inhibits the central and peripheral effects of apomorphine, induces release of prolactin and produces a transient increase in circulating aldosterone levels.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following intravenous administration, the onset of action is within 1 to 3 minutes and after intramuscular administration, this interval is extended to 10 to 15 minutes. The effect usually lasts from 1 to 2 hours.

Distribution.

Plasma protein binding is 13% to 22%.

Metabolism.

About 80% of the drug is excreted in the urine in the first 24 hours after administration. Approximately half is unchanged metoclopramide and half is the glucuronide and sulphate conjugate.

Excretion.

Metabolism mainly occurs in the liver and elimination half-life may vary from 2.5 to 6 hours. Impaired renal function results in a reduced clearance and an increased half-life, up to 15 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, water for injections.
When necessary, pH is adjusted with sodium hydroxide and/or hydrochloric acid.

6.2 Incompatibilities

See Section 4.2 Dose and Method of Administration, Method of administration.
If the standard formulation of metoclopramide is used for the treatment of nausea and vomiting associated with cytotoxic drugs, the cytotoxic agent should be administered as a separate infusion.

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 25°C. Protect from light.
If ampoules are removed from their carton, they should be stored away from light. If inadvertent exposure occurs, ampoules showing a yellow discolouration must be discarded.

6.5 Nature and Contents of Container

Metoclopramide Injection BP 10 mg in 2 mL (sterile) LDPE ampoules in packs of 10s or 50s.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Metoclopramide hydrochloride monohydrate occurs as a white or almost white, crystalline powder or crystals, very soluble in water, freely soluble in alcohol, sparingly soluble in methylene chloride, practically insoluble in ether.
Chemical name: 4-amino-5-chloro-N-(2-diethylaminoethyl)-2- methoxybenzamide hydrochloride monohydrate.
The structural formula is:

Chemical structure.


Molecular formula: C14H22ClN3O2.HCl.H2O.
Molecular weight: 354.3.

CAS number.

54143-57-6.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes