Consumer medicine information

Metomax

Metoclopramide hydrochloride; Paracetamol

BRAND INFORMATION

Brand name

Metomax

Active ingredient

Metoclopramide hydrochloride; Paracetamol

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metomax.

What is in this leaflet

This leaflet answers some common questions about METOMAX.

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 or pharmacist has weighed the risks of you taking METOMAX against the benefits expected for you.

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

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

What METOMAX is used for

METOMAX is used to treat nausea experienced with migraine headaches.

Migraine is a condition that is thought to be caused by the widening of certain blood vessels in the brain causing a recurrent headache that normally affects one side of the head.

Migraines are usually described as intense, throbbing or pounding pain that involves the temple, but can sometimes be located in the forehead, around the eye or the back of the head.

There are many symptoms that may accompany migraines; nausea (feeling sick) is one of the most common.

METOMAX contains paracetamol and metoclopramide hydrochloride (as monohydrate).

Paracetamol is an analgesic, used for temporary relief from pain (such as headache). Metoclopramide is an anti-emetic, used to control nausea and vomiting caused by migraine.

Ask your doctor or pharmacist if you have any questions about why METOMAX has been recommended for you. Your doctor or pharmacist may have recommended METOMAX for another reason.

This medicine is not addictive.

METOMAX is a "Pharmacist Only Medicine". It is available without a doctor's prescription but your pharmacist's advice is required.

Before you take METOMAX

When you must not take it

Do not take METOMAX if you are allergic to:

  • paracetamol (e.g. Panadol)
  • metoclopramide (e.g. Maxolon, Pramin)
  • any of the ingredients listed at the end of this leaflet.

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 METOMAX if you have:

  • bleeding from the stomach and/or digestive tract
  • intestinal blockage
  • recent surgery on the stomach and/or intestine
  • phaeochromocytoma, a rare tumour of the adrenal gland. The adrenal gland is located near the kidney.

Do not use if you have epilepsy (fits).

Do not give METOMAX to children under 18 years.

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

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

Before you start to take it

Tell your doctor or pharmacist if you are allergic to any other medicines, foods, dyes or preservatives.

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

Tell your doctor or pharmacist if you are breastfeeding or wish to breastfeed. METOMAX passes into breast milk, and although the effect on your baby is not known, there is a possibility that your breastfed baby may be affected.

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

  • epilepsy
  • breast cancer
  • Parkinson's disease, a condition affecting muscle control and movement
  • kidney or liver problems
  • 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. METOMAX should not be taken immediately after certain types of operations.

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

Taking other medicines

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

Some medicines and METOMAX 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
  • other paracetamol containing products.

These medicines may be affected by METOMAX 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 more information on medicines to be careful with or avoid while taking this medicine.

How to take METOMAX

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

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

Take METOMAX strictly as directed by your doctor or pharmacist.

The initial dose for adults is 1-2 capsules. METOMAX should be taken at the first sign of a migraine attack. If symptoms persist, repeat every four hours.

The maximum dose for adults is 6 capsules in 24 hours.

Do not take more than the recommended dose.

Your dose may be different from those on the pack, depending on your condition and whether or not you are taking any other medicines. Your doctor or pharmacist will advise you.

METOMAX is not recommended for children below 18 years of age.

How to take it

Swallow the capsules whole with a full glass of water.

When to take it

Take METOMAX at the first sign of a migraine attack.

How long to take it for

METOMAX is not intended for long-term use.

Do not take for more than a few days at time unless advised to buy a doctor.

If you take too much (overdose)

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

There is a risk of delayed, serious liver damage. You may need urgent medical attention.

If you take too much METOMAX, you may feel dizzy, sleepy or drowsy, confused, sweaty, vomit, have pains in the stomach, have convulsions or fits, or experience uncontrolled muscle movements or notice yellowing of the skin.

While you are taking METOMAX

Things you must do

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

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

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

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

Things you must not do

Do not use METOMAX to treat any other complaints unless your doctor or pharmacist tells you to.

Do not give this medicine to anyone else, even if they have similar symptoms.

Do not take METOMAX with any other products containing paracetamol, unless advised to do so by a doctor or pharmacist.

Things to be careful of

Be careful driving or operating machinery until you know how METOMAX affects you. METOMAX 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.

Avoid drinking alcohol while taking METOMAX. Combining METOMAX with alcohol can make you more sleepy or drowsy.

Side effects

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

METOMAX helps most people to relieve some of the symptoms associated with their migraines. But it may have unwanted side effects in some people.

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

Do not be alarmed by the following 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 or pharmacist if you notice any of the following and they worry you:

  • indigestion
  • drowsiness
  • fatigue, tiredness
  • restlessness
  • trouble sleeping
  • dizziness, headache
  • feeling sick, also called nausea
  • bowel irregularities.

The above list includes the milder side effects of METOMAX.

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

  • unusual changes mood, such as anxiety, depression or agitation
  • uncontrolled and 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.

The above list includes serious side effects which may require medical attention or hospitalisation.

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

  • symptoms of an allergic reaction such as, skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath
  • 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
  • severe drowsiness or sleepiness
  • bluish colouration to the skin, a symptom of blood condition called methaemoglobinaemia.

The side effects listed above are rare, but serious and require urgent medical attention or hospitalisation.

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

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

After taking METOMAX

Storage

Keep METOMAX where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your capsules in the pack until it is time to take them. If you take the capsules out of the pack they will not keep well.

Keep your capsules in a cool dry place where the temperature stays below 25°C.

Do not store METOMAX or any other medicine in the bathroom or near a sink.

Do not leave METOMAX in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor or pharmacist tells you to stop taking METOMAX, or your capsules have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

METOMAX is a capsule marked with a Greek alpha symbol on the green section and "P500|M5" on the yellow section.

Each pack contains 10 capsules.

Ingredients

The active ingredient in METOMAX capsules is paracetamol 500 mg and metoclopramide hydrochloride 5 mg (as metoclopramide hydrochloride monohydrate).

The capsules also contain the following inactive ingredients:

  • colloidal anhydrous silica
  • magnesium stearate
  • purified talc
  • sodium starch glycollate
  • black ink (PI 2328, 2343)
  • gelatin capsule size 0 (PI 11306).

METOMAX contains sulfites.

Supplier

METOMAX is supplied in Australia by:

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

Australian registration number:

METOMAX - AUST R 121343

METOMAX® is a Viatris company trade mark

This leaflet was prepared in December 2021.

METOMAX_cmi\Dec21/00

Published by MIMS January 2022

BRAND INFORMATION

Brand name

Metomax

Active ingredient

Metoclopramide hydrochloride; Paracetamol

Schedule

S3

 

1 Name of Medicine

Paracetamol.
Metoclopramide hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Metomax capsules contain the active ingredients paracetamol and metoclopramide hydrochloride monohydrate.
Each Metomax capsule contains 500 mg paracetamol and 5.25 mg metoclopramide hydrochloride monohydrate equivalent to 5 mg metoclopramide hydrochloride.

Excipients with known effect.

Sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Metomax Capsules: The capsules are size 0, hard gelatin capsules with a green cap and yellow body. Printed in black ink is "α" on the cap and "P500/M5" on the body.

4 Clinical Particulars

4.1 Therapeutic Indications

Symptomatic relief of headache, nausea and vomiting associated with migraine.

4.2 Dose and Method of Administration

Metomax should be taken at the first warning of a migraine headache. 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 should not normally exceed 0.5 mg/kg bodyweight with a maximum of 30 mg daily. Metomax should only be used after careful examination to avoid masking an underlying disorder e.g. cerebral irritation.
Maximum treatment duration is 5 days. Keep to the recommended dose. Do not use for longer than a few days at a time unless advised to by a doctor.

Adults 18 years and over.

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

Children and adolescents under 18 years.

Metomax is not recommended for use in children under 18 years.

Renal and hepatic impairment.

Therapy should be initiated at half the normal dose since adverse effects are likely to be exacerbated. The dose should then be adjusted depending on the clinical response.

4.3 Contraindications

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.
Known hypersensitivity or intolerance to paracetamol, metoclopramide or any of the excipients in Metomax capsules.
Children and adolescence under 18 years.
Insufficient safety data exist to support the use of Metomax (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

Persistent tardive dyskinesia.

Tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high dose therapy, especially females. The symptoms are persistent and can oftentimes appear to be irreversible. The syndrome is characterised by rhythmical involuntary movement of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities. There is no known effective treatment for tardive dyskinesia; however, in some patients symptoms may lessen or resolve after metoclopramide treatment is stopped. Antiparkinson agents usually do not alleviate the symptoms of this syndrome.
Although the risk of tardive dyskinesia with metoclopramide has not been extensively studied, one published study reported a tardive dyskinesia prevalence of 20% among patients treated for at least 3 months. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the total cumulative dose.
Metoclopramide therapy should routinely be discontinued in patients who develop signs or symptoms of tardive dyskinesia. It has been suggested that fine vermicular movements of the tongue may be an early sign of the syndrome, and, if the medication is stopped at that time, the syndrome may not develop. Tardive dyskinesia may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. Metoclopramide itself, however, may suppress (or partially suppress) the signs of tardive dyskinesia, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of the syndrome is unknown. Therefore, metoclopramide should not be used for the symptomatic control of tardive dyskinesia.
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.

Epilepsy.

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

Dystonia.

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

Neuroleptic malignant syndrome.

Has been reported with metoclopramide in combination with antipsychotics, 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 one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhoea, amenorrhoea, gynaecomastia and impotence have been reported with prolactin elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of prolactin stimulating antipsychotic drugs.
Neither clinical studies nor epidemiological studies conducted to date, however, 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.

Parkinson's disease.

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

Surgery.

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

Masking of serious illness.

The symptomatic relief provided by metoclopramide may delay recognition of serious disease. This product should not be prescribed or recommended 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 Metomax, the patient should be reassessed to exclude the possibility of an underlying disorder, e.g. cerebral irritation.

Other paracetamol containing products.

Patients should be warned not to take this product with other paracetamol containing products.

Use in hepatic or renal impairment.

Metomax 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.

See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects).

Paediatric use.

Metomax is not recommended for use in children and adolescents under 18 years of age.
There is a higher incidence of adverse events from metoclopramide in children (see Section 4.3 Contraindications).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Paracetamol.

Anticoagulants.

Anticoagulant dosage may require reduction if treatment with Metomax 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.

Metoclopramide.

Anticholinergic drugs and narcotic (opioid-containing) analgesics.

The effects of metoclopramide on gastrointestinal motility can be antagonised by these.

CNS depressants.

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

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, levodopa), whereas absorption of drugs from the stomach may be diminished (e.g. digoxin).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Pregnancy Category: metoclopramide hydrochloride (Category A), paracetamol (Category A).

Metoclopramide/ paracetamol combination.

Insufficient safety data exist to support the use of Metomax (metoclopramide/ paracetamol combination) in pregnancy (see Section 4.3 Contraindications).
Australian categorisation of Category A. Drugs that have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
 This product should only be used in breastfeeding mothers when the expected benefits to the mother outweigh any potential risk to the baby. Paracetamol and metoclopramide are both excreted in breast milk.
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 exist to support the use of Metomax (metoclopramide/ paracetamol 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 this product.

4.8 Adverse Effects (Undesirable Effects)

Paracetamol.

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.

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 (less than 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 such as benztropine or an anticholinergic antihistamine such as 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 (less than 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). This medicine should 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.

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.

Toxic symptoms of paracetamol overdose include 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, hepatoxicity may occur after ingestion of a single dose of paracetamol 10 to 15 g (20 to 30 capsules or 10 to 15 times the normal dose); a dose of 25 g (50 capsules) 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.
Extrapyramidal side effects are the most 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, methods of reducing absorption of ingested drug are important. Prompt administration of activated charcoal 50 g in 150 mL of water and 150 mL sorbitol 50% solution by mouth may reduce absorption. It is recommended that intravenous fluids such as normal saline be given concurrently. Gastric lavage is indicated if the patient is unwilling or unable to drink an activated charcoal/ sorbitol mixture.
If the history suggests that paracetamol 15 g or more has been ingested, administer the following antidote. Intravenous acetylcysteine 20%. Administer acetylcysteine immediately without waiting for positive urine test or plasma level results if 8 hours or less since overdose ingestion. Initial dose 150 mg/kg over 15 minutes, followed by continuous infusion of 50 mg/kg in glucose 5% 500 mL over four hours and 100 mg/kg in glucose 5% 1 L over 16 hours.
If more than 8 hours have elapsed since the overdosage was taken, the antidote may be less effective.
When treatment for paracetamol toxicity has been initiated; antiparkinson and antihistamine/ anticholinergic drugs such as diphenhydramine hydrochloride can be administered to effectively control extrapyramidal reactions of metoclopramide. Haemodialysis appears ineffective in removing metoclopramide. Similarly, continuous ambulatory peritoneal dialysis does not remove significant amounts of the drug.
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.

Paracetamol is a para-aminophenol derivative that exhibits analgesic and antipyretic activity. It does not possess anti-inflammatory activity.
Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary or pancreatic secretions. Its mode of action is unclear. It seems to sensitise tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.
Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower oesophageal sphincter. It has little, if any effect on the motility of the colon or gall bladder.
Metoclopramide has dopamine antagonist activity. Like the phenothiazines and related drugs, which are also dopamine antagonists, metoclopramide produces sedation and may produce extrapyramidal reactions (see Section 4.4 Special Warnings and Precautions for Use). Metoclopramide inhibits the central and peripheral effects of apomorphine, induces release of prolactin and causes a transient increase in circulating aldosterone levels.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Paracetamol.

Absorption.

After oral administration, paracetamol is absorbed rapidly and completely from the gastrointestinal tract; peak plasma concentrations occur 20 to 120 minutes after administration, with a mean value of about 51 minutes.

Distribution.

Paracetamol is uniformly distributed throughout most body fluids; the apparent volume of distribution is 1 to 1.2 L/kg.
Paracetamol can cross the placenta and is excreted in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.

Metabolism.

Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). A minor proportion (less than 20%) is metabolised to catechol derivatives and mercapturic acid compounds via oxidation.

Excretion.

Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol with 85 to 90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1.9 to 5.7 hours, with a mean value of about 3.2 hours. Food intake delays paracetamol absorption.

Metoclopramide.

The onset of pharmacological action is 30 to 60 minutes following an oral dose.

Absorption.

After oral administration, the peak plasma concentrations occur in 38 minutes to 2.5 hours, with a mean value of about 1 hour.

Distribution.

Metoclopramide is excreted in breast milk. Plasma protein binding is 13 to 22%.

Metabolism.

About 80% of the drug is excreted in the urine in the first 24 hours, approximately half as the glucuronide and sulfate conjugates and half as unchanged drug.

Excretion.

The elimination half-life varies from 3.2 to 14 hours, with a mean value of about 6.7 hours. Impaired renal function results in reduced clearance of metoclopramide and an increased half-life (15 hours).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Colloidal anhydrous silica, magnesium stearate, purified talc, sodium starch glycollate, black ink (PI 2328, 2343), gelatin capsule size 0 (PI 11306).

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 25°C.

6.5 Nature and Contents of Container

Metomax capsules.

Container type: PVC/PVDC/Al blisters.
Pack size: 10 capsules.

Australian register of therapeutic goods (ARTG).

AUST R 121343 - Metomax capsule blister pack.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Paracetamol.


Chemical name: N-(4-hydroxyphenyl)acetamide. Molecular formula: C8H9NO2. Molecular weight: 151.2.

CAS number.

103-90-2.
Paracetamol is a white crystalline powder, sparingly soluble in water, freely soluble in alcohol, very slightly soluble in ether and in methylene chloride.

Metoclopramide hydrochloride monohydrate.


Chemical name: 4-amino-5-chloro-N-(2-diethylaminoethyl)-2- methoxybenzamide hydrochloride monohydrate. Molecular formula: C14H22ClN3O2,HCl,H2O. Molecular weight: 354.3.

CAS number.

54143-57-6.
Metoclopramide hydrochloride is 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.

7 Medicine Schedule (Poisons Standard)

S3 (Pharmacist Only Medicine).

Summary Table of Changes