Consumer medicine information

Anagraine

Metoclopramide hydrochloride; Paracetamol

BRAND INFORMATION

Brand name

Anagraine

Active ingredient

Metoclopramide hydrochloride; Paracetamol

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Anagraine.

SUMMARY CMI

ANAGRAINE

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 using ANAGRAINE?

ANAGRAINE contains the active ingredients metoclopramide (as metoclopramide hydrochloride) and paracetamol. ANAGRAINE is used for the relief of headache, nausea, and vomiting associated with migraine.

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

2. What should I know before I use ANAGRAINE?

Do not use if you have ever had an allergic reaction to ANAGRAINE 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 use ANAGRAINE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ANAGRAINE 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 use ANAGRAINE?

  • The initial dosage for adults is one to two tablets and then 1-2 tablets every four hours, as needed. Do not take more than 6 tablets in 24 hours, and do not take it for longer than 48 hours at a time unless advised to by a doctor.
  • ANAGRAINE should be taken at the first sign of a migraine attack.
  • Swallow the tablet with a glass of water.

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

5. What should I know while using ANAGRAINE?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ANAGRAINE.
  • Tell your doctor or pharmacist if nausea, vomiting or headache persists.
Things you should not do
  • Do not give this medicine to anyone else, even if they have similar symptoms.
  • Do not take ANAGRAINE to treat any other complaints unless your doctor or pharmacist tells you to.
  • Do not take ANAGRAINE with other products containing paracetamol, unless advised to do so by a doctor or pharmacist.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how ANAGRAINE affects you.
Drinking alcohol
  • Avoid drinking alcohol while taking ANAGRAINE.
Looking after your medicine
  • Keep your tablets in the blister pack until it is time to take them.
  • Keep ANAGRAINE in a cool dry place, away from moisture or heat where the temperature stays below 30°C.

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

6. Are there any side effects?

Very common side effects of ANAGRAINE include restlessness, drowsiness, fatigue, and lethargy. Common side effects include insomnia, headache, dizziness, nausea, or bowel upsets. Serious side effects of ANAGRAINE include unusual changes in mood, different types of muscle spasms or rigidity, an allergic reaction, difficulty breathing, severe drowsiness/fatigue, or a bluish discolouration of the skin.

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

ANAGRAINE

Active ingredients: metoclopramide hydrochloride & paracetamol

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using ANAGRAINE?

ANAGRAINE contains the active ingredients metoclopramide (as metoclopramide hydrochloride) and paracetamol.

ANAGRAINE is used for the relief of headache, nausea and vomiting associated with migraine.

Metoclopramide helps control nausea and vomiting caused by migraine and other illnesses. It 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.

Paracetamol is an analgesic. It provides effective temporary relief from pain.

2. What should I know before I use ANAGRAINE?

Warnings

Do not use ANAGRAINE if:

  • you have any of the following health conditions:
    - porphyria (causing pain, nausea and vomiting)
    - pain in stomach, chest, legs or back
    - bleeding from the stomach and/or digestive tract
    - intestinal blockage
    - recent surgery on the stomach and/or digestive tract
    - phaeochromocytoma (a rare tumour of the adrenal gland)
    - epilepsy (fits).
  • you are allergic to metoclopramide, paracetamol or any of the ingredients listed at the end of this leaflet. Some symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue, or any other parts of the body; rash, itching or hives on the skin.
  • the expiry date printed on the pack has passed.
  • the packaging is torn or shows signs of tampering, or if the tablets do not look quite right.

Check with your doctor if you:

  • have any other medical conditions, especially the following:
    - epilepsy - metoclopramide may increase the risk of you having a fit
    - breast cancer
    - liver or kidney disease
    - Parkinson's disease
    - you have had movements that you cannot control, mainly of the tongue, mouth, jaw, arms and legs after taking metoclopramide or medicines used to calm emotional and mental problems.

Tell your doctor or pharmacist if you plan to have surgery.

ANAGRAINE should not be taken immediately after certain types of operations.

Tell your doctor or pharmacist if you have had any allergy to any other medicines, or any other substances, such as foods, preservatives, or dyes.

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

During treatment with ANAGRAINE, tell your doctor straight away if you have severe illnesses, including severe renal impairment or sepsis (when bacteria and their toxins circulate in the blood leading to organ damage), or you suffer from malnutrition, chronic alcoholism or if you are also taking flucloxacillin (an antibiotic). A serious condition called metabolic acidosis (a blood and fluid abnormality) has been reported in patients in these situations when paracetamol is used at regular doses for a prolonged period or when paracetamol is taken together with flucloxacillin. Symptoms of metabolic acidosis may include: serious breathing difficulties with deep rapid breathing, drowsiness, feeling sick (nausea) and being sick (vomiting).

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

Do not take ANAGRAINE if you are pregnant or intend to become pregnant.

It may affect the developing baby if you take it during pregnancy.

Do not take ANAGRAINE if you are breastfeeding or intend to breastfeed.

ANAGRAINE passes into breast milk and therefore may harm the baby.

Use in children

Do not give this medicine to children and adolescents under 18 years of age.

The safety of this medicine in children under 18 years of age has not been established.

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 ANAGRAINE may interfere with each other. These include:

  • medicines used to prevent blood clots
  • medicines used to treat epilepsy
  • pain relievers such as codeine and morphine
  • some medicines found in travel sickness, hayfever and allergy, stomach cramps and, cough and cold preparations
  • medicines used to treat anxiety or help you to sleep medicines used to treat certain mental and emotional conditions, such as schizophrenia
  • tetracycline antibiotics
  • levodopa, a medicine used in the treatment of Parkinson's disease
  • digoxin, a medicine used to treat heart failure
  • flucloxacillin (antibiotic), due to a serious risk of blood and fluid abnormality (called metabolic acidosis) that must have urgent treatment (see section 2),
  • other paracetamol containing products.

These medicines may be affected by ANAGRAINE 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 or pharmacist has a more complete list of medicines to avoid while taking ANAGRAINE.

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

4. How do I use ANAGRAINE?

How much to take

  • The initial dosage for adults is one to two tablets and then 1-2 tablets every four hours, as needed.
  • Do not take more than 6 tablets in 24 hours.
  • Do not take ANAGRAINE for longer than 48 hours at a time unless advised to by a doctor.

When to take ANAGRAINE

ANAGRAINE should be taken at the first sign of a migraine attack.

If you forget to use ANAGRAINE

If symptoms persist, take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you use too much ANAGRAINE

If you think that you have used too much ANAGRAINE, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), 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 using ANAGRAINE?

Things you should do

  • Tell your doctor or pharmacist if nausea, vomiting or headache persists.
  • Tell all doctors, dentists and pharmacists who are treating you that you are taking ANAGRAINE.
  • If you are about to be started on any new medicine, tell your doctor or pharmacist that you are taking ANAGRAINE
  • Tell your doctor or pharmacist straight away if you become pregnant

Things you should not do

  • Do not take ANAGRAINE for longer than 48 hours at a time unless advised to by a doctor.
  • Do not give this medicine to anyone else, even if they have similar symptoms.
  • Do not take ANAGRAINE to treat any other complaints unless your doctor or pharmacist tells you to.
  • Do not take ANAGRAINE with other products containing paracetamol, unless advised to do so by a doctor or pharmacist.

No more than 4 g of paracetamol should be taken in any 24 hours period.

Driving or using machines

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

ANAGRAINE may cause drowsiness, tiredness or dizziness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

Avoid drinking alcohol while taking ANAGRAINE.

Combining ANAGRAINE with alcohol can make you more sleepy or drowsy.

Looking after your medicine

Keep your tablets in the original container, protected from light where the temperature stays below 30°C.

Store in a cool dry place, away from moisture or heat. For example, do not store it:

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

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

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

Do not use this medicine after the expiry date.

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, dizziness restlessness, fatigue
  • bowel upsets
  • trouble sleeping
  • upset stomach
  • dizziness, headache.
  • jaundice (yellowing of the eyes or skin)
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
  • anxiety, depression, or agitation
  • repeated movements of the arms, legs, eyes, mouth, tongue, face and jaw. This may be a sign of tardive dyskinesia, a movement disorder which can be potentially irreversible.
  • A serious condition that can make blood more acidic (called metabolic acidosis), in patients with severe illness using paracetamol (see section 2)
Call your doctor straight away if you notice any of these serious side effects.
This includes serious side effects which may require medical attention or hospitalisation
  • symptoms of an allergic reaction such as, skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath
  • a sudden increase in body temperature, extremely high blood pressure, stiff muscles and severe convulsions. These could be signs of a serious side effect called neuroleptic malignant syndrome
  • spasms of facial muscles, lockjaw, slurred speech, involuntary eye movements, unnatural positioning of the head and shoulders, severe arching from the neck and back, and general muscle stiffness.
  • Parkinson's-like symptoms, including muscle tremors, rigidity, and slowness or inability of movement.
  • wheezing and difficulty breathing
  • severe drowsiness or sleepiness
  • bluish colouration to the skin, a symptom of blood condition called methaemoglobinaemia
Call your doctor straight away or go to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.
These side effects are rare, but serious and require urgent medical attention or hospitalisation.

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.

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 available from your pharmacist.

What ANAGRAINE contains

Active ingredients
(main ingredients)
  • metoclopramide hydrochloride: 5 mg/tablet
  • paracetamol: 500 mg/tablet
Other ingredients
(inactive ingredients)
  • magnesium stearate
  • sodium starch glycollate

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

What ANAGRAINE looks like

ANAGRAINE tablets are round, white and scored on one side. They are available in blister packs of 8 tablets.

Australian Registration number: AUST R 13547

Who distributes ANAGRAINE

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

This leaflet was revised in June 2025.

Published by MIMS July 2025

BRAND INFORMATION

Brand name

Anagraine

Active ingredient

Metoclopramide hydrochloride; Paracetamol

Schedule

S3

 

1 Name of Medicine

Metoclopramide hydrochloride and paracetamol.

2 Qualitative and Quantitative Composition

Each Anagraine tablet contains 5 mg metoclopramide and 500 mg paracetamol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablet, white, round, flat, 12 mm in diameter with a score line on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

For the symptomatic relief of headache, nausea and vomiting associated with migraine.

4.2 Dose and Method of Administration

Anagraine should be taken at the first warning of a migraine attack. If symptoms persist, further doses may be taken at four-hourly intervals. Total dosage in any 24 hour period should not exceed the quantity stated.
The dosage recommendations given below should be strictly adhered to if side effects of the dystonic type are to be avoided. It should be noted that a total daily dosage of metoclopramide, especially for adolescents and young adults, should not normally exceed 0.5 mg/kg bodyweight.

Adults.

The recommended dose is one or two tablets initially, and then one or two tablets every 4 hours (maximum dose of 6 tablets in 24 hours).

4.3 Contraindications

Known hypersensitivity or intolerance to paracetamol, metoclopramide or any of the excipients in Anagraine.
Wherever stimulation of gastrointestinal motility might be dangerous, e.g. in the presence of gastrointestinal haemorrhage, mechanical obstruction or perforation.
Stimulation of gastrointestinal motility may aggravate these conditions.
Phaeochromocytoma. Hypertensive crisis have been reported with the use of metoclopramide in these patients. This is probably due to the release of catecholamines from the tumour. Such hypertensive crises may be controlled by phentolamine.
Epilepsy. The frequency and severity of seizures may be increased in epileptic patients given metoclopramide. Metoclopramide should not be used in patients with epilepsy since it may increase the frequency and severity of seizures.
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.
Children and adolescents under 18 years of age.
Insufficient safety data exists to support the use of Anagraine (metoclopramide/ paracetamol combination) in pregnancy or during lactation (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Paracetamol. Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
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.

Persistent tardive dyskinesia.

Tardive dyskinesia may occur in some patients following 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 in some patients 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 the extremities. There is no known effective treatment for tardive dyskinesia; antiparkinson agents usually do not alleviate the symptoms of this syndrome.
If these symptoms appear, it is suggested that the dosage of all antipsychotic or other antidopaminergic agents be progressively reduced with a view to discontinuation if possible. Should it be necessary to reinstitute treatment, increase the dosage of the agent, or switch to a different antidopaminergic agent, the syndrome may be masked. 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.
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.

Neuroleptic malignant syndrome.

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

Breast cancer and prolactin levels.

Metoclopramide elevates prolactin levels and the elevation persists during chronic administration. Tissue culture experiments indicate that approximately 1/3 of human breast cancers are prolactin dependent in vitro, a factor of potential importance if 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 tumorigenesis; the available evidence is too limited to be conclusive at this time.

Epilepsy.

The frequency and severity of seizures or extrapyramidal reactions may be increased in epileptic patients given metoclopramide.

Surgery.

Following operations such as pyloroplasty or gut anastomosis, metoclopramide therapy should be withheld for 3 or 4 days as vigorous muscular contractions may not help healing.

Parkinson's disease.

Metoclopramide can exacerbate Parkinsonian symptoms, hence should be used with caution, if at all, in patients with Parkinsonian syndrome.

Masking of serious illness.

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

Anagraine should be administered with caution to patients with renal or hepatic dysfunction.
Plasma concentrations of paracetamol and its conjugates are increased in patients with moderate renal failure. In patients with clinically significant degrees of renal or hepatic impairment, the clearance of metoclopramide is likely to be reduced (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

Anagraine should not be given to children and adolescents under 18 years of age. There is a higher incidence of adverse reactions from metoclopramide in this age group.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Metoclopramide.

Anticholinergic drugs and narcotic (opioid-containing) analgesics.

The effects of metoclopramide on gastrointestinal motility are antagonised by anticholinergic drugs and narcotic analgesics.

CNS depressants.

Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics or tranquillizers.

Drugs affected by increased gastrointestinal motility.

Since metoclopramide accelerates abnormally slow gastric and small bowel peristaltic activity, it may change absorption of orally administered drugs. The absorption of drugs from the small bowel may be accelerated (e.g. paracetamol, tetracycline, l-dopa), whereas absorption of drugs from the stomach may be diminished (e.g. digoxin).

Paracetamol.

Anticoagulants.

Anticoagulant dosage may require reduction if paracetamol medication is prolonged.
Paracetamol absorption is increased by drugs which increase gastric emptying, e.g. metoclopramide, and decreased by drugs which decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties, narcotic analgesics. Paracetamol may increase chloramphenicol concentrations.

Enzyme inducing agents.

The likelihood of paracetamol toxicity may be increased by the concomitant use of enzyme inducing agents such as alcohol or anticonvulsant drugs.

Concomitant use with flucloxacillin.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see Section 4.4).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Insufficient safety data exists on Anagraine (metoclopramide/ paracetamol combination) (see Section 4.3 Contraindications).

Metoclopramide.

Category A. Adequate human data on use during pregnancy are not available for metoclopramide.

Paracetamol.

Category A.
 Paracetamol and metoclopramide are both excreted in breast milk.
Paracetamol is excreted in breast milk. The amount available for ingestion by the infant has been reported variously as less than 0.1% of a single dose of paracetamol 500 mg, and as 0.04 to 0.23% of a single 650 mg dose. Maternal ingestion of paracetamol in usual analgesic doses does not appear to present a risk to the breastfed infant. It is not known whether it has a harmful effect on the newborn. The administration of metoclopramide to breastfeeding mothers may increase the risk of adverse reactions in young children and should be taken into account when making a risk-benefit assessment.
Insufficient safety data exists to support the use of Anagraine (paracetamol/ metoclopramide combination) during lactation (see Section 4.3 Contraindications.)

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 taking Anagraine.

4.8 Adverse Effects (Undesirable Effects)

Metoclopramide.

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, nausea, or bowel disturbances may occur. Rare (< 1 in 1,000) cases of acute depression have been reported. Anxiety or agitation may occur.
Raised serum prolactin levels have been observed during metoclopramide therapy; this effect is similar to that noted with many other compounds.
Although uncommon at normal dosage, various extrapyramidal reactions to metoclopramide, usually of the dystonic type, have been reported. 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 crises, 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 (e.g. benztropine) or an anticholinergic antihistamine (e.g. diphenhydramine) should be given.
Tardive dyskinesia which may be persistent, has been reported, particularly in elderly patients undergoing long-term therapy with metoclopramide.
Very rare (< 1 in 10,000) occurrences of the neuroleptic malignant syndrome have been reported. This syndrome is potentially fatal and comprises hyperpyrexia, altered consciousness, muscle rigidity, autonomic instability and elevated levels of creatine phosphokinase (CPK) and must be treated urgently (recognised treatments include dantrolene and bromocriptine). Anagraine must be stopped immediately if this syndrome occurs.
Methaemoglobinaemia has also been reported.
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.
There have been isolated reports of hypersensitivity reactions (such as urticaria, maculopapular rash) in patients receiving metoclopramide.
There have been a few cases of neutropenia, leucopenia and agranulocytosis generally without clear cut relationship to metoclopramide.
Sulfhaemoglobinaemia in adults.
Hyperthermia has also been observed.
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.
Respiratory failure, secondary to dystonic reaction, acute asthmatic symptoms of wheezing and dyspnoea may occur.
Urinary incontinence and frequency, sexual dysfunction, priapism and muscle spasm may also occur.
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.

Paracetamol.

High anion gap metabolic acidosis: frequency "not known".
Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see Section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.
Reports of adverse reactions are rare. Although the following reactions have been reported, a causal relationship to the administration of paracetamol has been neither confirmed nor refuted: dyspepsia, nausea, allergic and haematological reactions.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

In the case of paracetamol, toxic symptoms including vomiting, abdominal pain, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma.
Paracetamol overdose can result in severe liver damage and sometimes acute renal tubular necrosis.
In adults, hepatotoxicity may occur after ingestion of a single dose of paracetamol 10 to 15 g; a dose of 25 g or more is potentially fatal. Symptoms during the first two days of acute poisoning by paracetamol do not reflect the potential seriousness of the intoxication. Major manifestations of liver failure such as jaundice, hypoglycaemia and metabolic acidosis may take at least three days to develop. Liver damage and death may occur.
Extrapyramidal side effects are more frequently reported adverse reactions to metoclopramide overdosage. Very rarely AV block has been observed.

Treatment.

Prompt treatment is essential even when there are no obvious symptoms.
Treatment consists primarily of management of paracetamol toxicity. Gastric emptying, close observation and supportive therapy is the management plan of choice for metoclopramide intoxication.
In cases of overdosage, management should consist of reducing the absorption of ingested drug, close observation and supportive therapy. Prompt administration of activated charcoal may reduce absorption. Methionine and acetylcysteine may be used as antidotes if given within a few hours of paracetamol overdosage. Antiparkinson and antihistamine/ anticholinergic drugs such as diphenhydramine hydrochloride have effectively controlled extrapyramidal reactions.
Haemodialysis appears ineffective in removing metoclopramide. Similarly, continuous ambulatory peritoneal dialysis does not remove significant amounts 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

Mechanism of action.

Metoclopramide stimulates gastrointestinal tract motility and accelerates gastric emptying and intestinal transit and has been shown to increase the speed of absorption of paracetamol. Metoclopramide also possesses dopamine antagonist activity. It is useful in the symptomatic relief of nausea and vomiting.
Paracetamol is an analgesic useful in the relief of pain associated with migraine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Magnesium stearate and sodium starch glycollate.

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

Packed in blister packs of 8 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Paracetamol.


Metoclopramide hydrochloride.


CAS number.

Paracetamol: 103-90-2; metoclopramide hydrochloride: 7232-21-5.

7 Medicine Schedule (Poisons Standard)

S3 - 8 tablets.

Summary Table of Changes