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.

What is in this leaflet

This leaflet answers some common questions about Anagraine. It does not contain all the available information. It does not take the place of talking to your pharmacist or doctor.

All medicines have risks and benefits.

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

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

What Anagraine is used for

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

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

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.

There is no evidence that Anagraine is addictive.

Before you take it

When you must not take it

Do not take Anagraine if you have ever had an allergic reaction to:

  • metoclopramide
  • paracetamol
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include asthma, wheezing, shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, skin rash, itching or hives.

Do not take it if you have any of the following conditions:

  • 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).

Do not use if you have epilepsy (fits).

Do not take Anagraine if:

  • you are pregnant, or intend to become pregnant
    It may affect your developing baby if you take it during pregnancy.
  • you are breast-feeding or intend to breast-feed
    Anagraine passes into breast milk and therefore may harm the baby.

Do not take Anagraine after the expiry date (EXP) printed on the pack.

Do not take it if the packaging is torn or shows signs of tampering or if the tablets do not look quite right.

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.

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

Before you start to take it

Tell your doctor or pharmacist if:

  1. you have allergies to any other medicines, foods, preservatives or dyes.
  2. you have or have had any of the following medical conditions:
  • epilepsy - metoclopramide may increase the risk of you having a fit
  • breast cancer
  • liver or kidney disease
  • Parkinson's disease - metoclopramide may make this condition worse
  • 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.

If you have not told your doctor or pharmacist about any of the above, tell them before you take Anagraine.

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 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
  • 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.

How to take it

How much to take

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

Adults:
The initial dosage for adults is 1-2 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.

How to take it

Swallow the tablet with a glass of water.

If you forget to take it

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

Do not take a double dose to make up for the dose that 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 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 that you or anyone else may have taken too much Anagraine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Anagraine you may experience the following symptoms:

  • vomiting
  • stomach pain
  • sweating
  • low blood pressure
  • yellowing of the skin
  • drowsiness
  • confusion or fits
  • twitching or uncontrolled spasms.

While you are taking it

Things you must 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 immediately if you become pregnant while taking Anagraine.

Things you must 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.

Things to be careful of

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

Not more than 4 g of paracetamol should be taken in any 24 hour period.

Be careful driving or operating machinery 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.

Avoid drinking alcohol while taking Anagraine. Combining Anagraine 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 Anagraine. Anagraine helps most people with migraines but it may have some 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:

  • drowsiness, tiredness, dizziness restlessness, fatigue
  • bowel upsets
  • trouble sleeping
  • upset stomach
  • dizziness, headache.

The above list includes the milder side effects of Anagraine.

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 Anagraine 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 it

Storage

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

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store Anagraine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

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

Disposal

Dispose of the tablets where children cannot reach them.

If you stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

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

Ingredients

Active ingredients:
Each tablet contains 5 mg of metoclopramide hydrochloride anhydrous and 500 mg of paracetamol.

Inactive ingredients:

  • magnesium stearate
  • sodium starch glycollate.

Anagraine tablets do not contain lactose, gluten, tartrazine or any other azo dyes.

Sponsor

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

Australian Registration Number: AUST R 13547.

This leaflet was prepared in December 2023.

Published by MIMS January 2024

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.

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.

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.

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.

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