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.

What is in this leaflet

This leaflet answers some common questions about Metoclopramide Injection.

It does not contain all 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 Metoclopramide Injection against the benefits it is expected to have for you.

This medicine is likely to be used while you are at the clinic or in hospital. If possible, please read this leaflet carefully before this medicine is given to you. In some cases this leaflet may be given to you after the medicine has been used.

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

Keep this leaflet. You may need to read it again.

What Metoclopramide Injection is used for

What Metoclopramide Injection does

In adults over 20 years of age, Metoclopramide Injection is used 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 children and young adults under 20 years of age, Metoclopramide should be restricted to the following conditions and only used as second line therapy:

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

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

Metoclopramide Injection belongs to a group of medicines known as antiemetics. Antiemetics stop or prevent nausea and vomiting.

Metoclopramide Injection may be used for the management of other conditions that are not mentioned above.

Your doctor will be able to tell you about the specific condition for which you have been prescribed Metoclopramide Injection.

How Metoclopramide Injection works

This medicine works by blocking the action of a chemical in the brain which causes nausea and vomiting. It also acts in the stomach and upper intestine to increase muscle contractions.

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

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

Before you are given Metoclopramide Injection

When you must not be given it

Do not use Metoclopramide Injection if you have an allergy to any medicine containing:

  • any of the ingredients listed at the end of this leaflet
  • any other similar medicines, such as procaine, procainamide.

Some of the symptoms of an allergic reaction may include:

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

Do not take Metoclopramide Injection if you have any of 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.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes. Tell your doctor if you have or have had any of the following medical conditions:

  • 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.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Metoclopramide is excreted in breast milk, and can be absorbed by your baby if you are breast-feeding.

Your doctor can discuss with you the risks and benefits involved.

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

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by Metoclopramide Injection 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 will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

  • painkillers
  • sleeping tablets
  • certain drugs used to treat psychiatric disorders including depression
  • medicines for hay fever, other allergies or colds
  • 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.

Do not drink alcohol while you are being given Metoclopramide Injection. Your doctor will advise you about continuing to take other medicines while you are receiving Metoclopramide Injection.

How Metoclopramide Injection is given

Metoclopramide Injection is given by injection into the muscle or by slow injection into a vein.

Metoclopramide Injection must only be given by a doctor or nurse.

How long to have it

Continue having Metoclopramide Injection for as long as your doctor tells you. Your doctor will decide what dose and how long you will receive Metoclopramide Injection.

This may depend on your age, your condition and whether or not you are taking any other medicines.

If you are given too much (overdose)

Metoclopramide Injection is usually given to you in hospital under the supervision of a doctor it is unlikely that you will receive too much.

Immediately tell your doctor or telephone the Poisons Information Centre on 13 11 26 for advice, or go to Accident and Emergency at your nearest hospital, if you think that you may have had too much Metoclopramide Injection.

Symptoms of an overdose may include:

  • drowsiness, confusion
  • tremor, twitching or uncontrolled spasm of muscles.

While you are having Metoclopramide Injection

Things you must 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 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 immediately if you become pregnant while taking this medicine.

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 effects.

Things to be careful of

Be careful driving or operating machinery until you know how Metoclopramide Injection affects you. This medicine 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.

Be careful when drinking alcohol while you are having this medicine. If you drink alcohol, it may make you sleepy.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues, talk to your doctor.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given metoclopramide.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

It can be difficult to tell whether side effects are the result of having Metoclopramide Injection, effects of your condition or side effects of other medicines you may be taking. For this reason it is important to tell your doctor of any change in your condition.

Do not be alarmed by the list 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 if

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

  • drowsiness, tiredness
  • restlessness
  • dizziness
  • headache
  • nausea
  • bowel irregularities
  • insomnia.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if

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

  • fast heartbeat
  • depression, suicidal thoughts.

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

Go to hospital if

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • 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.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

It is important to keep your routine doctor's appointments. Some side effects may only be seen by your doctor. You may need regular blood test.

After being given Metoclopramide Injection

Storage

Metoclopramide Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light where the temperature stays below 25°C.

Disposal

Metoclopramide Injection is usually given in a hospital setting. Your pharmacist will dispose of left over Metoclopramide Injection.

Product description

What it looks like

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

Metoclopramide Injection contains metoclopramide hydrochloride 5 mg/mL and sodium chloride in water for injections. It does not contain a preservative.

Who manufactures and distributes Metoclopramide Injection

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

Australian registration number

10 mg/2 mL: AUST R 11364

Date of preparation

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